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D72798
|
http://homeguides.sfgate.com/would-lose-pressure-well-81982.html
|
Why Would You Lose Pressure to a Well?
|
"Related Articles How to Get More Pressure Out of Well Water How to Troubleshoot Residential Well Problems How to Set Up a Home Jet Pump With a Pressure Tank How to Create Better Water Flow in Your Home Typical residential water pressure averages about 50 pounds per square inch. Private wells sometimes deliver less pressure than municipal water supplies. Symptoms of low well-water pressure include noticeable declines when two outlets simultaneously are opened -- such as when shower water pressure plummets because someone flushes a toilet elsewhere in the home. Another symptom of low well pressure is very slow fill times for washing machines and toilet tanks, and/or air spurting when faucets are opened. Plumbing Issues A common cause of low well pressure is a clogged sediment filter located in the supply line after the pump. In some cases, the pressure switch that activates and deactivates the pump at preset water pressure levels also may have a blockage from sediment or mineral accumulation in the pressure sensor tube. This may cause the pump to fail to activate or deactivate at the correct water pressure. Leaks or blockages in pipes or devices installed in the plumbing such as water softening equipment also reduces water pressure. Pressure Tank Problems The well pressure tank sustains consistent water pressure into the home without continuously running the pump. An inflated air bladder inside the storage tank imposes pressure on well water in the tank. As the water level in the tank drops from household demand, pressure in the tank declines to a preset minimum. The well pump then actuates to pump more water into the tank and restore pressure. An under-inflated air bladder results in lower water pressure output from the tank. Well-pressure tanks provide an automotive-style Schrader air valve on the top or the side where bladder pressure can be verified with a standard air gauge. References (2)Inspect APedia: Diagnostic Guide for Poor Water Pressure Inspect APedia: How a Bad Water Tank Can Cause Pressure Loss About the Author Gus Stephens has written about aviation, automotive and home technology for 15 years. His articles have appeared in major print outlets such as ""Popular Mechanics"" and ""Invention & Technology."" Along the way, Gus earned a Bachelor of Arts in communications. If it flies, drives or just sits on your desk and blinks, he's probably fixed it. Photo Credits Jupiterimages/Photos.com/Getty Images Cite this Article "
|
[
"\"Related Articles How to Get More Pressure Out of Well Water How to Troubleshoot Residential Well Problems How to Set Up a Home Jet Pump With a Pressure Tank How to Create Better Water Flow in Your Home Typical residential water pressure averages about 50 pounds per square inch.",
"Private wells sometimes deliver less pressure than municipal water supplies.",
"Symptoms of low well-water pressure include noticeable declines when two outlets simultaneously are opened -- such as when shower water pressure plummets because someone flushes a toilet elsewhere in the home.",
"Another symptom of low well pressure is very slow fill times for washing machines and toilet tanks, and/or air spurting when faucets are opened.",
"Plumbing Issues A common cause of low well pressure is a clogged sediment filter located in the supply line after the pump.",
"In some cases, the pressure switch that activates and deactivates the pump at preset water pressure levels also may have a blockage from sediment or mineral accumulation in the pressure sensor tube.",
"This may cause the pump to fail to activate or deactivate at the correct water pressure.",
"Leaks or blockages in pipes or devices installed in the plumbing such as water softening equipment also reduces water pressure.",
"Pressure Tank Problems The well pressure tank sustains consistent water pressure into the home without continuously running the pump.",
"An inflated air bladder inside the storage tank imposes pressure on well water in the tank.",
"As the water level in the tank drops from household demand, pressure in the tank declines to a preset minimum.",
"The well pump then actuates to pump more water into the tank and restore pressure.",
"An under-inflated air bladder results in lower water pressure output from the tank.",
"Well-pressure tanks provide an automotive-style Schrader air valve on the top or the side where bladder pressure can be verified with a standard air gauge.",
"References (2)Inspect APedia: Diagnostic Guide for Poor Water Pressure Inspect APedia: How a Bad Water Tank Can Cause Pressure Loss About the Author Gus Stephens has written about aviation, automotive and home technology for 15 years.",
"His articles have appeared in major print outlets such as \"\"Popular Mechanics\"\" and \"\"Invention & Technology.\"\"",
"Along the way, Gus earned a Bachelor of Arts in communications.",
"If it flies, drives or just sits on your desk and blinks, he's probably fixed it.",
"Photo Credits Jupiterimages/Photos.com/Getty Images Cite this Article \""
] |
D2166931
|
https://www.quora.com/Why-is-cat-not-mans-best-friend
|
Why is cat not man's best friend?
|
"Ovidiu Savescu Answered May 24, 2013It has a lot to do with each species' evolved behaviors and social system in the wild along a great deal of time: - dogs have evolved to live and hunt in tight-knit packs with a clear hierarchy of power led by the alpha male. They hunt in packs, most often taking on prey that is bigger than any one individual member. Hence, cooperation, teamwork, and an authority structure are vital for survival of all individuals. - cats on the other hand have evolved to live in loose associations and almost always hunt alone (with some exceptions). When they do cooperate they do it as a temporary alliance of equals, not a clearly structured hunting party like canines do. A cat can very well survive on it's own because cats generally hunt prey smaller and weaker than themselves. Remember, we're talking about the wild here, and the way each species evolved. From the above differences stem the different behaviors of current day domestic dogs and cats. It's simply in their genes. Dogs see their owner as the ""alpha"" or head of the pack since they manage to ""magically make food appear"". Also, dogs display both submissive and cooperative behavior because that's the best way their genes know to strengthen the pack and survive. The reason why a dog is considered ""man's best friend"" is that their social structure is very similar to base human tribal social structure and the affection they display (designed to strengthen the pack) is compatible with the human notion of friendship (which is one of the ways human social groups are formed). Man (as a species), dog and cat are all selfish beasts, all we do is for our own personal gain, even things like charity and affectionate behavior or loyalty. The difference is that for homo sapiens and dogs helping the pack is helping yourself, while for cats that is not true. So they don't do it.998 Views · View Upvoters Related Questions More Answers Below If dogs can talk, are they still man's best friend? What are the benefits of having my cat as my best friend? Why are dogs called ""man's best friend? ""Is dog man's best friend? Tell me your stories? Apart from dogs, what else qualifies as man's best friend? Ask New Question Aditya Nanda, had a pet cat, had a pet dog Answered May 24, 2013 · Author has 320 answers and 835.7k answer views A dog's is called Man's best friend while cats are not because dogs are much more faithful and understanding. You will mean far more to your dog than to your pet cat. A dog depends on you in a way that cats don't. Contrasted to pet dogs, cats just don't give much of a shit about you. Of course there are exceptions. This is not to say that cats or other pets aren't faithful but just not as much as a canine. Further, dogs have been domesticated by humans for a long time (more than 20,000 years ago). Dogs can be trained to do a variety of jobs that most other animals can't. Hence, a dog is a man's best friend. Hachi: A Dog's Tale is a beautiful movie which showcases the relationship between a man and his pet dog.1.5k Views · View Upvoterspromoted by The Great Courses Plus - Direct Experience the joy of self-improvement. Take steps toward gradual, lasting, goal-oriented change using cognitive behavioral therapy. Learn More at thegreatcourses.com Peter Wallace Answered Aug 23, 2017 · Author has 1.2k answers and 310k answer views Part of it is the natural and artificial evolution of the cat. Most species of cats are solitary animals and rarely get together in groups. The cat-human relationship isn’t a very strong one because it never needed to be one. Cats moved in because early human settlements were infested with rodents. Humans kept them around with a little bit of food. Cats are very, very low maintenance animals. Leave a big bowl of food/water and you can leave them for a week. Come back and they treat you just the same as you left. Give a couple more thousand years and a strict breeding regimen, cats might be as reliable as dogs.88 Views Yehudit Hasin, own dogs on and off all my life. Proud owner of a dog and a cat. Answered May 24, 2013 · Author has 421 answers and 539k answer views Because humans adopted dogs, while cats adopted humans...... :)Yu977 Views · View Upvoters "
|
[
"\"Ovidiu Savescu Answered May 24, 2013It has a lot to do with each species' evolved behaviors and social system in the wild along a great deal of time: - dogs have evolved to live and hunt in tight-knit packs with a clear hierarchy of power led by the alpha male.",
"They hunt in packs, most often taking on prey that is bigger than any one individual member.",
"Hence, cooperation, teamwork, and an authority structure are vital for survival of all individuals.",
"- cats on the other hand have evolved to live in loose associations and almost always hunt alone (with some exceptions).",
"When they do cooperate they do it as a temporary alliance of equals, not a clearly structured hunting party like canines do.",
"A cat can very well survive on it's own because cats generally hunt prey smaller and weaker than themselves.",
"Remember, we're talking about the wild here, and the way each species evolved.",
"From the above differences stem the different behaviors of current day domestic dogs and cats.",
"It's simply in their genes.",
"Dogs see their owner as the \"\"alpha\"\" or head of the pack since they manage to \"\"magically make food appear\"\".",
"Also, dogs display both submissive and cooperative behavior because that's the best way their genes know to strengthen the pack and survive.",
"The reason why a dog is considered \"\"man's best friend\"\" is that their social structure is very similar to base human tribal social structure and the affection they display (designed to strengthen the pack) is compatible with the human notion of friendship (which is one of the ways human social groups are formed).",
"Man (as a species), dog and cat are all selfish beasts, all we do is for our own personal gain, even things like charity and affectionate behavior or loyalty.",
"The difference is that for homo sapiens and dogs helping the pack is helping yourself, while for cats that is not true.",
"So they don't do it.998 Views · View Upvoters Related Questions More Answers Below If dogs can talk, are they still man's best friend?",
"What are the benefits of having my cat as my best friend?",
"Why are dogs called \"\"man's best friend?",
"\"\"Is dog man's best friend?",
"Tell me your stories?",
"Apart from dogs, what else qualifies as man's best friend?",
"Ask New Question Aditya Nanda, had a pet cat, had a pet dog Answered May 24, 2013 · Author has 320 answers and 835.7k answer views A dog's is called Man's best friend while cats are not because dogs are much more faithful and understanding.",
"You will mean far more to your dog than to your pet cat.",
"A dog depends on you in a way that cats don't.",
"Contrasted to pet dogs, cats just don't give much of a shit about you.",
"Of course there are exceptions.",
"This is not to say that cats or other pets aren't faithful but just not as much as a canine.",
"Further, dogs have been domesticated by humans for a long time (more than 20,000 years ago).",
"Dogs can be trained to do a variety of jobs that most other animals can't.",
"Hence, a dog is a man's best friend.",
"Hachi: A Dog's Tale is a beautiful movie which showcases the relationship between a man and his pet dog.1.5k Views · View Upvoterspromoted by The Great Courses Plus - Direct Experience the joy of self-improvement.",
"Take steps toward gradual, lasting, goal-oriented change using cognitive behavioral therapy.",
"Learn More at thegreatcourses.com Peter Wallace Answered Aug 23, 2017 · Author has 1.2k answers and 310k answer views Part of it is the natural and artificial evolution of the cat.",
"Most species of cats are solitary animals and rarely get together in groups.",
"The cat-human relationship isn’t a very strong one because it never needed to be one.",
"Cats moved in because early human settlements were infested with rodents.",
"Humans kept them around with a little bit of food.",
"Cats are very, very low maintenance animals.",
"Leave a big bowl of food/water and you can leave them for a week.",
"Come back and they treat you just the same as you left.",
"Give a couple more thousand years and a strict breeding regimen, cats might be as reliable as dogs.88 Views Yehudit Hasin, own dogs on and off all my life.",
"Proud owner of a dog and a cat.",
"Answered May 24, 2013 · Author has 421 answers and 539k answer views Because humans adopted dogs, while cats adopted humans...... :)Yu977 Views · View Upvoters \""
] |
D2809775
|
http://www.investopedia.com/terms/b/barratry.asp
|
DEFINITION of 'Barratry'
|
"DEFINITION of 'Barratry'An illegal act whereby an attorney instigates a dispute or otherwise encourages the filing of a lawsuit, in order to profit from legal fees. Barratry typically involves the filing of a groundless claim in order to receive payment from clients. It is an illegal practice in all U. S. states and subject to criminal punishment and discipline by the state bar. An attorney found guilty of barratry would generally face disbarment. Next Up Special Power Of Attorney Financial Power Of Attorney Ambulance Chaser Tying BREAKING DOWN 'Barratry'Barratry refers to an attorney's illegal instigation of lawsuits with no legitimate claim. For barratry to be a criminal act, the accused must perform repeated and persistent acts of litigation. It is against the law for an attorney to look for accident victims in hospitals or at home in an attempt to solicit business. Such ""ambulance chasers"" could be found guilty of barratry. RELATED TERMSSpecial Power Of Attorney Special power of attorney is a written authorization that grants ... Financial Power Of Attorney A financial power of attorney grants a trusted agent the authority ... Ambulance Chaser In insurance, a derogatory term for lawyers and other service ... Tying An often illegal arrangement where, in order to buy one product, ... Insurance Defense Insurance defense refers to Attorneys who focus on representing ... Power of Attorney of Property A legal document transferring the legal right to the attorney ... Related Articles Managing Wealth Got a Financial Windfall? Hire the Right Attorney Selecting the right attorney will help you protect your assets when you receive a sudden windfall. Investing Attention Home Buyers: Why You Need a Lawyer Property transactions are complex and subject to specific state/local rules. Hiring a lawyer can simplify the process. Financial Advisor How To Pick The Right Lawyer Find out what factors to consider before hiring an attorney. Retirement The Importance of Durable Financial Power of Attorney Having a durable financial power of attorney in place can save you from having the court decide who handles your finances when you can't. Managing Wealth Why Keep Medical & Financial Powers of Attorney Separate? Representing your interests in financial matters is a very different job from communicating and advocating for your wishes with doctors. Investing5 Free Or Low-Cost Legal Services Legal fees have never been more expensive. Here are some ways for you to save on legal fees while still getting reliable advice. Retirement Tip for Estate Planning on the Cheap Estate planning is an expensive but necessary process for everyone with assets they’d like to eventually distribute. Here's how to keep it affordable. Small Business Hiring A Really Competent Patent Attorney Use this guide to find a well-qualified attorney to guide your application through the complex patenting process at the best possible price. Retirement4 Estate Planning Documents You Need to Have Here's the lowdown on the four essential legal documents you need – right now – to have in place before you die. Small Business Don't get sued: 5 tips to protect your small business Find out what you can do to limit risk and keep your business running smoothly. How to avoid a lawsuit and the actions to take to protect your company. RELATED FAQSWhat do real estate attorneys do? Understand the role of a real estate attorney to help you decide if you would benefit from the expertise of this type of ... Read Answer >>What exactly is insider trading? Two common misconceptions are that all insider trading is illegal and that insider trading and insider information are the ... Read Answer >> "
|
[
"\"DEFINITION of 'Barratry'An illegal act whereby an attorney instigates a dispute or otherwise encourages the filing of a lawsuit, in order to profit from legal fees.",
"Barratry typically involves the filing of a groundless claim in order to receive payment from clients.",
"It is an illegal practice in all U. S. states and subject to criminal punishment and discipline by the state bar.",
"An attorney found guilty of barratry would generally face disbarment.",
"Next Up Special Power Of Attorney Financial Power Of Attorney Ambulance Chaser Tying BREAKING DOWN 'Barratry'Barratry refers to an attorney's illegal instigation of lawsuits with no legitimate claim.",
"For barratry to be a criminal act, the accused must perform repeated and persistent acts of litigation.",
"It is against the law for an attorney to look for accident victims in hospitals or at home in an attempt to solicit business.",
"Such \"\"ambulance chasers\"\" could be found guilty of barratry.",
"RELATED TERMSSpecial Power Of Attorney Special power of attorney is a written authorization that grants ... Financial Power Of Attorney A financial power of attorney grants a trusted agent the authority ... Ambulance Chaser In insurance, a derogatory term for lawyers and other service ... Tying An often illegal arrangement where, in order to buy one product, ... Insurance Defense Insurance defense refers to Attorneys who focus on representing ... Power of Attorney of Property A legal document transferring the legal right to the attorney ... Related Articles Managing Wealth Got a Financial Windfall?",
"Hire the Right Attorney Selecting the right attorney will help you protect your assets when you receive a sudden windfall.",
"Investing Attention Home Buyers: Why You Need a Lawyer Property transactions are complex and subject to specific state/local rules.",
"Hiring a lawyer can simplify the process.",
"Financial Advisor How To Pick The Right Lawyer Find out what factors to consider before hiring an attorney.",
"Retirement The Importance of Durable Financial Power of Attorney Having a durable financial power of attorney in place can save you from having the court decide who handles your finances when you can't.",
"Managing Wealth Why Keep Medical & Financial Powers of Attorney Separate?",
"Representing your interests in financial matters is a very different job from communicating and advocating for your wishes with doctors.",
"Investing5 Free Or Low-Cost Legal Services Legal fees have never been more expensive.",
"Here are some ways for you to save on legal fees while still getting reliable advice.",
"Retirement Tip for Estate Planning on the Cheap Estate planning is an expensive but necessary process for everyone with assets they’d like to eventually distribute.",
"Here's how to keep it affordable.",
"Small Business Hiring A Really Competent Patent Attorney Use this guide to find a well-qualified attorney to guide your application through the complex patenting process at the best possible price.",
"Retirement4 Estate Planning Documents You Need to Have Here's the lowdown on the four essential legal documents you need – right now – to have in place before you die.",
"Small Business Don't get sued: 5 tips to protect your small business Find out what you can do to limit risk and keep your business running smoothly.",
"How to avoid a lawsuit and the actions to take to protect your company.",
"RELATED FAQSWhat do real estate attorneys do?",
"Understand the role of a real estate attorney to help you decide if you would benefit from the expertise of this type of ... Read Answer >>What exactly is insider trading?",
"Two common misconceptions are that all insider trading is illegal and that insider trading and insider information are the ... Read Answer >> \""
] |
D93787
|
http://www.bestplaces.net/cost_of_living/state/iowa
|
Cost of Living
|
Cost of Living Download .xls COST OF LIVING OVERVIEWOur cost of living indices are based on a US average of 100. An amount below 100 means Iowa, State is cheaper than the US average. A cost of living index above 100 means Iowa, State is more expensive. Iowa, State cost of living is 87.50. Housing is the biggest factor in the cost of living difference. See the Iowa housing market: Homes For Sale Apartments Single Family Rentals COST OF LIVING Iowa, Iowa United States Overall 88 100Grocery97 100View More Data >COST OF LIVING MAPPlease Sign up or Log In to use maps. ORReviews for Iowa Unknown Iowa Mouse over the stars for your rating and click to rate. 1=Not a Fan. 2=Not for Me. 3=Just Okay. 4=Great Place. 5=The Best Place. Start Your Review of Iowa, IALisa Marshalltown, IASend Message1/25/2016Cost of Living Reviewing Cost of Living in... (Read More)303 266Reply | No Replies Kathy Cambridge, IASend Message4/8/2015Season Changes Truly have the distinct 4 seasons here. The cold makes you appreciate the summer even more! Spring can be cold, icy and frigid. The following Spring can bring 70-80... (Read More)235 254Reply | No Repliesmatt Maquoketa, IASend Message1/9/2015nothing to do Iowa is a boring state unless you like to hike. Winters are... (Read More)311 304Reply | No Replies Read all reviews about Iowa
|
[
"Cost of Living Download .xls COST OF LIVING OVERVIEWOur cost of living indices are based on a US average of 100.",
"An amount below 100 means Iowa, State is cheaper than the US average.",
"A cost of living index above 100 means Iowa, State is more expensive.",
"Iowa, State cost of living is 87.50.",
"Housing is the biggest factor in the cost of living difference.",
"See the Iowa housing market: Homes For Sale Apartments Single Family Rentals COST OF LIVING Iowa, Iowa United States Overall 88 100Grocery97 100View More Data >COST OF LIVING MAPPlease Sign up or Log In to use maps.",
"ORReviews for Iowa Unknown Iowa Mouse over the stars for your rating and click to rate.",
"1=Not a Fan.",
"2=Not for Me.",
"3=Just Okay.",
"4=Great Place.",
"5=The Best Place.",
"Start Your Review of Iowa, IALisa Marshalltown, IASend Message1/25/2016Cost of Living Reviewing Cost of Living in... (Read More)303 266Reply | No Replies Kathy Cambridge, IASend Message4/8/2015Season Changes Truly have the distinct 4 seasons here.",
"The cold makes you appreciate the summer even more!",
"Spring can be cold, icy and frigid.",
"The following Spring can bring 70-80... (Read More)235 254Reply | No Repliesmatt Maquoketa, IASend Message1/9/2015nothing to do Iowa is a boring state unless you like to hike.",
"Winters are... (Read More)311 304Reply | No Replies Read all reviews about Iowa"
] |
D2383330
|
http://boatspecs.iboats.com/Starcraft_Marine__Capri_15__1972/bp/66b86056
|
1972 Starcraft Marine Capri 15
|
1972 Starcraft Marine Capri 15The 1972, Capri 15 is a 15.08 foot outboard boat. The weight of the boat is 762 lbs. which does not include passengers, aftermarket boating accessories, or fuel. The max rated horsepower of this boat, as listed by the manufacturer, (according to records we have) is 85 hp . If you do not have the manual for your engine then we highly recommend that you get one as repowering is costly and it takes you off of the water. When repowering, it is best to verify this information for the sake of safety and to ensure that your insurance company will cover you. While this runabout does have a hull made of fiberglass, it is beneficial to keep the boat clean and dry by covering it properly while not in use. Good maintenance and care can help your vessel stay in good condition and have a higher value at resale. Applicable engine information has been included below since a boat needs reliable power. Information on this page is provided to you as a free service of iboats.com. Because this information has come from many sources we can not guarantee its accuracy. Even if this information is the same as the original factory specs, boats are sometimes modified. Thus, for safety and other reasons, it is a good idea to verify information here to make sure it matches up with your boat. For additional information, we recommend the iboats forums and a boating safety course. Engine Information: Boat Max HP : 85 hp Repair Manuals: Propellers: Engine Parts: Parts, Accessories & Upgrades to Consider: Would these parts and accessories improve your boating and experience? Boating Tubes Boating is all about having fun. Boating tubes offer a lot of excitement and fun. Tube sports can be rather extreme, so be sure to play it safe! Boat Seats If mildew, cracks, and punctures are taking over those old boat seats, here are some seats to consider as replacements. Life Jackets Safety on the water is a concern of all. With life jackets for adults, women, youth, children, fishermen, and dogs, there all plenty of choices! Power Trim and Tilt Do you need power trim and tilt on your outboard? Whether you want to add trim and tilt or repalace your OEM trim and tilt, we recommend one of these units. (note hp ratings) Starcraft Marine Rub Rails Get a brand new, great looking rub rail for your Starcraft Marine Boat Information on this page has come from multiple third parties and can not be guaranteed to be accurate.
|
[
"1972 Starcraft Marine Capri 15The 1972, Capri 15 is a 15.08 foot outboard boat.",
"The weight of the boat is 762 lbs.",
"which does not include passengers, aftermarket boating accessories, or fuel.",
"The max rated horsepower of this boat, as listed by the manufacturer, (according to records we have) is 85 hp .",
"If you do not have the manual for your engine then we highly recommend that you get one as repowering is costly and it takes you off of the water.",
"When repowering, it is best to verify this information for the sake of safety and to ensure that your insurance company will cover you.",
"While this runabout does have a hull made of fiberglass, it is beneficial to keep the boat clean and dry by covering it properly while not in use.",
"Good maintenance and care can help your vessel stay in good condition and have a higher value at resale.",
"Applicable engine information has been included below since a boat needs reliable power.",
"Information on this page is provided to you as a free service of iboats.com.",
"Because this information has come from many sources we can not guarantee its accuracy.",
"Even if this information is the same as the original factory specs, boats are sometimes modified.",
"Thus, for safety and other reasons, it is a good idea to verify information here to make sure it matches up with your boat.",
"For additional information, we recommend the iboats forums and a boating safety course.",
"Engine Information: Boat Max HP : 85 hp Repair Manuals: Propellers: Engine Parts: Parts, Accessories & Upgrades to Consider: Would these parts and accessories improve your boating and experience?",
"Boating Tubes Boating is all about having fun.",
"Boating tubes offer a lot of excitement and fun.",
"Tube sports can be rather extreme, so be sure to play it safe!",
"Boat Seats If mildew, cracks, and punctures are taking over those old boat seats, here are some seats to consider as replacements.",
"Life Jackets Safety on the water is a concern of all.",
"With life jackets for adults, women, youth, children, fishermen, and dogs, there all plenty of choices!",
"Power Trim and Tilt Do you need power trim and tilt on your outboard?",
"Whether you want to add trim and tilt or repalace your OEM trim and tilt, we recommend one of these units.",
"(note hp ratings) Starcraft Marine Rub Rails Get a brand new, great looking rub rail for your Starcraft Marine Boat Information on this page has come from multiple third parties and can not be guaranteed to be accurate."
] |
D2849164
|
https://en.wikipedia.org/wiki/War_Memorial_Stadium_(Arkansas)
|
War Memorial Stadium (Arkansas)
|
"War Memorial Stadium– AT&T Field Location 1 Stadium Drive Little Rock, AR 72205Coordinates 34°44′59.5″N92°19′48.0″WCoordinates: 34°44′59.5″N 92°19′48.0″WOwner State of Arkansas Operator Arkansas Department of Parks and Tourism Capacity 54,120 (2010–present) 53,727 (1991–2009) 53,645 (1988–1990) 53,250 (1986–1987) 53,555 (1967–1985) 40,000 (1960–1966) 31,075 (1948–1959)Record attendance 55,912 (September 19, 1992 vs. Alabama) [1]Field size 360 by 160 feet (110 m × 49 m)Surface Field Turf Construction Broke ground 1947Opened September 18, 1948 [4]Renovated 2010Construction cost $1.2 million ($12.2 million in 2017 dollars [2])Architect Bruce R. Anderson [3]Tenants Arkansas Razorbacks ( NCAA) (1948–present) Arkansas Baptist College Buffaloes ( NJCAA) (2007–present) Little Rock Rangers ( NPSL) (2016–present) Catholic High School Rockets ( AAA)Websitewww.wmstadium.com War Memorial Stadium is a multi-purpose stadium in Little Rock, Arkansas. The stadium is primarily used for American football and is the home stadium for the Arkansas Baptist Buffaloes, Catholic High School Rockets, Little Rock Rangers and the secondary home stadium for the University of Arkansas Razorbacks. The Arkansas State Red Wolves have also played there in the past. [5] The stadium also hosts the Delta Classic, an annual football game between the University of Arkansas at Pine Bluff Golden Lions and the Grambling State Tigers, as well as hosting the Arkansas Activities Association high school championship game in all classification. [6]Contents [ hide ]1 History2 Other uses2.1 Concerts2.2 Speaking engagements3 Notable events3.1 Aluminum Bowl4 See also5 References6 External links History [ edit]War Memorial Stadium finished construction in 1947 and had a seating capacity of 31,075. On September 19, 1948, the stadium was formally dedicated by former Arkansas Razorback and Medal of Honor recipient Maurice Britt. Britt dedicated the stadium to ""the memory of her native sons and daughters who have given so much that we might have our freedom."" [7] Following the dedication ceremony, the first game at the stadium commenced, where the Arkansas Razorbacks defeated the Abilene Christian Wildcats by a score of 40–6. War Memorial Stadium during a Catholic High School football game. War Memorial Stadium has added numerous improvements to the stadium and to the playing field. A complete lighting system and an Astro Turf surface were installed for the 1970 season. A new artificial surface was installed in 1974 and also again prior to the 1984 season, before a returning to natural grass field in 1994. [4] Artificial turf was reinstalled prior to the 2002 season when Astro Play was installed. A new scoreboard and video screen were added prior to the 2005 football season and the field was later upgraded to field turf in 2006. [8]Renovations to the club facility and press box began on December 14, 2009, following the 4A Arkansas Activities Association high school football championship game. [9] The renovations cost approximately $7.3 million and was completed in August 2010. The renovations also included the Sports Media Legends Wall of Honor, honoring Arkansas sports journalists that distinguished themselves in their careers and have made contributions to the stadium and to the sport. [10]AT&T signed a sponsorship agreement with the War Memorial Stadium Commission to name the playing field AT&T Field on June 23, 2010. The naming rights of the playing field last for at least five years with an option for a 10-year agreement. [11] With this agreement, War Memorial Stadium will earn $175,000 per year for the first five years with a 2.5% annual increase after the initial five years. [12]Other uses [ edit]In addition to athletics, the stadium has been used for a variety of other purposes including musical concerts and speaking engagements. Concerts [ edit]In 1995, Billy Joel and Elton John performed to a sell-out crowd of 41,274, grossing over $1.6 million for concert promotor Cellar Door Concerts. [13] Other artists who had performed at the stadium are The Eagles, The Rolling Stones, George Strait, and 'N Sync, among others. [14] [15]Speaking engagements [ edit]Reverend Billy Graham conducted his evangelistic crusades to thousands of listeners at the stadium that included a young Bill Clinton in 1959. [16] Graham returned to the stadium in 1989. Notable events [ edit]Aluminum Bowl [ edit]Main article: Aluminum Bowl Months prior to the 1956 collegiate football season, the National Association of Intercollegiate Athletics (NAIA) began searching for cities to host the inaugural NAIA championship game. As it appeared that the championship game was headed to Shreveport, Louisiana, the Louisiana legislature passed a bill banning integrated sporting events in the state. [17] This would cause the NAIA to look for another city to host the game because some of their member colleges had African-American athletes. War Memorial Stadium general manager Allen Berry had already begun to get local business to support for the game and the Little Rock Chamber of Commerce raised $25,000 to back the game. [17] Both Aluminum Company of America and Reynolds Metals Company agreed to pay $25,000 each to CBS to broadcast the game nationally and this agreement led to the game's name, the Aluminum Bowl. [17] The NAIA invited the Montana State University Bobcats and St. Joseph's College Pumas, the two leading NAIA football teams at that time, to play on December 22, 1956. [18] [19] The final result was a scoreless tie, and the teams were named NAIA co-champions for the 1956 season. Despite promotion of the game by local organizers, only 5,000 spectators attended the game; organizers failed to keep the championship game in Little Rock and the game was moved to St. Petersburg, Florida in 1957. [17] [20]See also [ edit]Arkansas portal Barton Coliseum Jack Stephens Center References [ edit]^ Carter, Mark (July 28, 2009). ""War Memorial: A One-Day Lambeau South?"". Arkansas Sports 360. Retrieved December 30, 2010.^ Federal Reserve Bank of Minneapolis Community Development Project. ""Consumer Price Index (estimate) 1800–"". Federal Reserve Bank of Minneapolis. Retrieved January 2, 2018.^ Horton, Aaron D. (November 5, 2012). ""War Memorial Stadium"". Encyclopedia of Arkansas History & Culture. Retrieved August 21, 2013.^ a b ""War Memorial Stadium"". University of Arkansas Media Relations. Retrieved January 3, 2011.^ astateredwolves.com^ Hunt, Donald (October 18, 2006). ""Arkansas-Pine Bluff surprises Grambling State"". ESPN.^ ""War Memorial Stadium, Little Rock, Pulaski County"". Arkansas Historic Preservation Program. Retrieved December 30, 2010.^ ""Arkansas to play on new Field Turf surface in '06"". Associated Press. ESPN. June 15, 2006. Retrieved January 3, 2011.^ ""Press Box Construction Begins"" (Press release). December 11, 2009. Retrieved January 3, 2011.^ ""War Memorial Stadium Honors Sports Media Legends"". KATV. September 10, 2010. Retrieved January 3, 2011.^ Lesnick, Gavin (June 23, 2010). ""AT&T buys naming rights for War Memorial field"". Arkansas Democrat-Gazette. Retrieved January 3, 2011.^ ""War Memorial Stadium Commission, AT&T Sign Naming Rights Pact for Surface of Historic Stadium"". Newport Television. Fox16.com. June 24, 2010. Retrieved January 3, 2011.^ ""Amusement Business: Boxscore Top 10 Grosses"". Billboard. Nielsen Business Media, Inc. 107 (17): 13. April 29, 1995. ISSN 0006-2510. Retrieved December 30, 2010.^ ""Homes Sweet Homes"". University of Arkansas Media Relations. Retrieved January 3, 2011.^ ""Pop Odyssey 2001 Tour Kicks Off Today"". Yahoo! Music. May 23, 2001. Retrieved January 3, 2011.^ Clinton, Bill (2004). My Life. New York: Knopf. p. 39. ISBN 0-375-41457-6.^ a b c d Edwards, Paul. ""Aluminum Bowl"". Encyclopedia of Arkansas History & Culture. Retrieved January 2, 2011.^ ""Coming Events Dec. 21 Through Jan. 4"". Sports Illustrated. December 24, 1956. Retrieved January 2, 2011.^ ""Football Program"". 2010-2011 NAIA Football Coach Manual (PDF). p. 8. Retrieved January 2, 2011.^ ""Past Champions"". 2010-2011 NAIA Football Coach Manual (PDF). p. 9. Retrieved January 2, 2011. External links [ edit]WMStadium.com - Official Website Google Maps Satellite Picture & Map of War Memorial Stadium [ show]v t e Arkansas Razorbacks football [ show]v t e Football stadiums of the Southeastern Conference [ show]v t e College football venues in Arkansas "
|
[
"\"War Memorial Stadium– AT&T Field Location 1 Stadium Drive Little Rock, AR 72205Coordinates 34°44′59.5″N92°19′48.0″WCoordinates: 34°44′59.5″N 92°19′48.0″WOwner State of Arkansas Operator Arkansas Department of Parks and Tourism Capacity 54,120 (2010–present) 53,727 (1991–2009) 53,645 (1988–1990) 53,250 (1986–1987) 53,555 (1967–1985) 40,000 (1960–1966) 31,075 (1948–1959)Record attendance 55,912 (September 19, 1992 vs. Alabama) [1]Field size 360 by 160 feet (110 m × 49 m)Surface Field Turf Construction Broke ground 1947Opened September 18, 1948 [4]Renovated 2010Construction cost $1.2 million ($12.2 million in 2017 dollars [2])Architect Bruce R. Anderson [3]Tenants Arkansas Razorbacks ( NCAA) (1948–present) Arkansas Baptist College Buffaloes ( NJCAA) (2007–present) Little Rock Rangers ( NPSL) (2016–present) Catholic High School Rockets ( AAA)Websitewww.wmstadium.com War Memorial Stadium is a multi-purpose stadium in Little Rock, Arkansas.",
"The stadium is primarily used for American football and is the home stadium for the Arkansas Baptist Buffaloes, Catholic High School Rockets, Little Rock Rangers and the secondary home stadium for the University of Arkansas Razorbacks.",
"The Arkansas State Red Wolves have also played there in the past.",
"[5] The stadium also hosts the Delta Classic, an annual football game between the University of Arkansas at Pine Bluff Golden Lions and the Grambling State Tigers, as well as hosting the Arkansas Activities Association high school championship game in all classification.",
"[6]Contents [ hide ]1 History2 Other uses2.1 Concerts2.2 Speaking engagements3 Notable events3.1 Aluminum Bowl4 See also5 References6 External links History [ edit]War Memorial Stadium finished construction in 1947 and had a seating capacity of 31,075.",
"On September 19, 1948, the stadium was formally dedicated by former Arkansas Razorback and Medal of Honor recipient Maurice Britt.",
"Britt dedicated the stadium to \"\"the memory of her native sons and daughters who have given so much that we might have our freedom.\"\"",
"[7] Following the dedication ceremony, the first game at the stadium commenced, where the Arkansas Razorbacks defeated the Abilene Christian Wildcats by a score of 40–6.",
"War Memorial Stadium during a Catholic High School football game.",
"War Memorial Stadium has added numerous improvements to the stadium and to the playing field.",
"A complete lighting system and an Astro Turf surface were installed for the 1970 season.",
"A new artificial surface was installed in 1974 and also again prior to the 1984 season, before a returning to natural grass field in 1994.",
"[4] Artificial turf was reinstalled prior to the 2002 season when Astro Play was installed.",
"A new scoreboard and video screen were added prior to the 2005 football season and the field was later upgraded to field turf in 2006.",
"[8]Renovations to the club facility and press box began on December 14, 2009, following the 4A Arkansas Activities Association high school football championship game.",
"[9] The renovations cost approximately $7.3 million and was completed in August 2010.",
"The renovations also included the Sports Media Legends Wall of Honor, honoring Arkansas sports journalists that distinguished themselves in their careers and have made contributions to the stadium and to the sport.",
"[10]AT&T signed a sponsorship agreement with the War Memorial Stadium Commission to name the playing field AT&T Field on June 23, 2010.",
"The naming rights of the playing field last for at least five years with an option for a 10-year agreement.",
"[11] With this agreement, War Memorial Stadium will earn $175,000 per year for the first five years with a 2.5% annual increase after the initial five years.",
"[12]Other uses [ edit]In addition to athletics, the stadium has been used for a variety of other purposes including musical concerts and speaking engagements.",
"Concerts [ edit]In 1995, Billy Joel and Elton John performed to a sell-out crowd of 41,274, grossing over $1.6 million for concert promotor Cellar Door Concerts.",
"[13] Other artists who had performed at the stadium are The Eagles, The Rolling Stones, George Strait, and 'N Sync, among others.",
"[14] [15]Speaking engagements [ edit]Reverend Billy Graham conducted his evangelistic crusades to thousands of listeners at the stadium that included a young Bill Clinton in 1959.",
"[16] Graham returned to the stadium in 1989. Notable events [ edit]Aluminum Bowl [ edit]Main article: Aluminum Bowl Months prior to the 1956 collegiate football season, the National Association of Intercollegiate Athletics (NAIA) began searching for cities to host the inaugural NAIA championship game.",
"As it appeared that the championship game was headed to Shreveport, Louisiana, the Louisiana legislature passed a bill banning integrated sporting events in the state.",
"[17] This would cause the NAIA to look for another city to host the game because some of their member colleges had African-American athletes.",
"War Memorial Stadium general manager Allen Berry had already begun to get local business to support for the game and the Little Rock Chamber of Commerce raised $25,000 to back the game.",
"[17] Both Aluminum Company of America and Reynolds Metals Company agreed to pay $25,000 each to CBS to broadcast the game nationally and this agreement led to the game's name, the Aluminum Bowl.",
"[17] The NAIA invited the Montana State University Bobcats and St. Joseph's College Pumas, the two leading NAIA football teams at that time, to play on December 22, 1956.",
"[18] [19] The final result was a scoreless tie, and the teams were named NAIA co-champions for the 1956 season.",
"Despite promotion of the game by local organizers, only 5,000 spectators attended the game; organizers failed to keep the championship game in Little Rock and the game was moved to St. Petersburg, Florida in 1957.",
"[17] [20]See also [ edit]Arkansas portal Barton Coliseum Jack Stephens Center References [ edit]^ Carter, Mark (July 28, 2009).",
"\"\"War Memorial: A One-Day Lambeau South?\"\".",
"Arkansas Sports 360.",
"Retrieved December 30, 2010.^ Federal Reserve Bank of Minneapolis Community Development Project.",
"\"\"Consumer Price Index (estimate) 1800–\"\".",
"Federal Reserve Bank of Minneapolis.",
"Retrieved January 2, 2018.^ Horton, Aaron D. (November 5, 2012).",
"\"\"War Memorial Stadium\"\".",
"Encyclopedia of Arkansas History & Culture.",
"Retrieved August 21, 2013.^ a b \"\"War Memorial Stadium\"\".",
"University of Arkansas Media Relations.",
"Retrieved January 3, 2011.^ astateredwolves.com^ Hunt, Donald (October 18, 2006).",
"\"\"Arkansas-Pine Bluff surprises Grambling State\"\".",
"ESPN.^ \"\"War Memorial Stadium, Little Rock, Pulaski County\"\".",
"Arkansas Historic Preservation Program.",
"Retrieved December 30, 2010.^ \"\"Arkansas to play on new Field Turf surface in '06\"\".",
"Associated Press.",
"ESPN.",
"June 15, 2006.",
"Retrieved January 3, 2011.^ \"\"Press Box Construction Begins\"\" (Press release).",
"December 11, 2009.",
"Retrieved January 3, 2011.^ \"\"War Memorial Stadium Honors Sports Media Legends\"\".",
"KATV.",
"September 10, 2010.",
"Retrieved January 3, 2011.^ Lesnick, Gavin (June 23, 2010).",
"\"\"AT&T buys naming rights for War Memorial field\"\".",
"Arkansas Democrat-Gazette.",
"Retrieved January 3, 2011.^ \"\"War Memorial Stadium Commission, AT&T Sign Naming Rights Pact for Surface of Historic Stadium\"\".",
"Newport Television.",
"Fox16.com.",
"June 24, 2010.",
"Retrieved January 3, 2011.^ \"\"Amusement Business: Boxscore Top 10 Grosses\"\".",
"Billboard.",
"Nielsen Business Media, Inc. 107 (17): 13.",
"April 29, 1995.",
"ISSN 0006-2510.",
"Retrieved December 30, 2010.^ \"\"Homes Sweet Homes\"\".",
"University of Arkansas Media Relations.",
"Retrieved January 3, 2011.^ \"\"Pop Odyssey 2001 Tour Kicks Off Today\"\".",
"Yahoo!",
"Music.",
"May 23, 2001.",
"Retrieved January 3, 2011.^ Clinton, Bill (2004).",
"My Life.",
"New York: Knopf.",
"p. 39.",
"ISBN 0-375-41457-6.^ a b c d Edwards, Paul.",
"\"\"Aluminum Bowl\"\".",
"Encyclopedia of Arkansas History & Culture.",
"Retrieved January 2, 2011.^ \"\"Coming Events Dec. 21 Through Jan. 4\"\".",
"Sports Illustrated.",
"December 24, 1956.",
"Retrieved January 2, 2011.^ \"\"Football Program\"\".",
"2010-2011 NAIA Football Coach Manual (PDF).",
"p. 8.",
"Retrieved January 2, 2011.^ \"\"Past Champions\"\".",
"2010-2011 NAIA Football Coach Manual (PDF).",
"p. 9.",
"Retrieved January 2, 2011.",
"External links [ edit]WMStadium.com - Official Website Google Maps Satellite Picture & Map of War Memorial Stadium [ show]v t e Arkansas Razorbacks football [ show]v t e Football stadiums of the Southeastern Conference [ show]v t e College football venues in Arkansas \""
] |
D914104
|
http://www.fastfoodmenuprices.com/how-to-save-money-with-fast-food/
|
How to Save Money with Fast Food
|
How to Save Money with Fast Food Posted on June 26, 2013 by Editorial Staff Fast food is thought to be the fastest and cheapest food you can buy. That will vary based on where you eat, what you choose, and other factors such as your location. But most of us eat meals from fast food restaurants, some more often than others. In this article, we’ll discuss some ways you can save money with fast food. It’s very easy to get caught up in their menus and one minute later, you’re out of $20 because you ordered a bunch of food you probably didn’t need in the first place. We will go over three main ways to save money with fast food: Eating in moderation and smaller portions. Giving cheap fast food options a try. Being on the lookout for fast food coupons. Eating in Moderation By now we all know that if you eat too much you’ll gain weight, possibly become obese, and even worse, be on a track of deteriorating health. So the best solution to this problem is to eat in moderation. Don’t be greedy!As hard as it is to resist tasty and inexpensive food, we have to be able to control how much we eat and how to say when it is enough. Remember, those same meals will be there waiting for you when you are hungry again so there’s no need to feel like you have to have a little bit of everything in one sitting. Try one meal tonight, and then a different meal the next time you go. As someone who eats fast food frequently, yet stays in good shape, I can’t recommend enough that eating in moderation is key to living a happy and healthy life. Even if you’re not eating fast food, you still need to keep in mind the word the phrase “eating in moderation.”Unless we discover food that has zero calories, you will have to be mindful and smart about what you eat and how much of it you eat. Giving Cheaper Fast Food Meals a Try I have talked to many people that said they don’t even look at the value menus in fast food restaurants. And that is a big mistake to make! Most people think that value menus are full of junk and the food is of lesser quality than rest of the menu. But the truth is that the quality is pretty much the same if you’re comparing apples to apples. Value menus are full of tasty and delicious foods, yet most are only between one and two dollars. Unless you just don’t care about how much you spend on food, I would definitely recommend trying food on the value and dollar menus next time. Another thing is that many value menu food items have similar ingredients as their higher-priced counterparts. For example, the Mc Double from Mc Donald’s is only one dollar and it is almost the exact same burger as the Double Cheeseburger, which can cost over $1.29. View the value menus we have showcased on our website so far: Mc Donald’s dollar menu Burger King value menu Be on the Lookout for Fast Food Coupons The same way you would save money at a grocery store using coupons, you can do the same when purchasing fast food. Most fast food restaurants offer coupons and your job is to find them if you want to save big bucks. Just to show you an example of how much of a difference a coupon can make, recently I bought 2 Jack’s Spicy Chicken sandwiches from Jack in the Box. With regular price, it would have cost me over $9 with tax. However, I was sneaky and pulled out a buy one Jack’s Spicy Chicken Sandwich, get one free coupon and ended up paying less than $5 with tax. That means I saved almost 50% of what I would have originally spent. Multiple my example above with number of times you eat at fast food restaurants per year and the savings can be quite substantial. You could be saving hundreds, if not thousands of dollars each year. As you can see, fast food coupons can be one of the most beneficial ways of saving money with fast food. If you need help finding coupons, read our previous article about how to find fast food coupons. Conclusion We just went over three great ways to save money with fast food, which includes eating in moderation, trying meals from the value menus, and using fast food coupons. Do you know of another way to save money with fast food? Share your thoughts in the comments. Fast Food Tips Tagged eat in moderation, fast food coupons, value menus
|
[
"How to Save Money with Fast Food Posted on June 26, 2013 by Editorial Staff Fast food is thought to be the fastest and cheapest food you can buy.",
"That will vary based on where you eat, what you choose, and other factors such as your location.",
"But most of us eat meals from fast food restaurants, some more often than others.",
"In this article, we’ll discuss some ways you can save money with fast food.",
"It’s very easy to get caught up in their menus and one minute later, you’re out of $20 because you ordered a bunch of food you probably didn’t need in the first place.",
"We will go over three main ways to save money with fast food: Eating in moderation and smaller portions.",
"Giving cheap fast food options a try.",
"Being on the lookout for fast food coupons.",
"Eating in Moderation By now we all know that if you eat too much you’ll gain weight, possibly become obese, and even worse, be on a track of deteriorating health.",
"So the best solution to this problem is to eat in moderation.",
"Don’t be greedy!As hard as it is to resist tasty and inexpensive food, we have to be able to control how much we eat and how to say when it is enough.",
"Remember, those same meals will be there waiting for you when you are hungry again so there’s no need to feel like you have to have a little bit of everything in one sitting.",
"Try one meal tonight, and then a different meal the next time you go.",
"As someone who eats fast food frequently, yet stays in good shape, I can’t recommend enough that eating in moderation is key to living a happy and healthy life.",
"Even if you’re not eating fast food, you still need to keep in mind the word the phrase “eating in moderation.”Unless we discover food that has zero calories, you will have to be mindful and smart about what you eat and how much of it you eat.",
"Giving Cheaper Fast Food Meals a Try I have talked to many people that said they don’t even look at the value menus in fast food restaurants.",
"And that is a big mistake to make!",
"Most people think that value menus are full of junk and the food is of lesser quality than rest of the menu.",
"But the truth is that the quality is pretty much the same if you’re comparing apples to apples.",
"Value menus are full of tasty and delicious foods, yet most are only between one and two dollars.",
"Unless you just don’t care about how much you spend on food, I would definitely recommend trying food on the value and dollar menus next time.",
"Another thing is that many value menu food items have similar ingredients as their higher-priced counterparts.",
"For example, the Mc Double from Mc Donald’s is only one dollar and it is almost the exact same burger as the Double Cheeseburger, which can cost over $1.29.",
"View the value menus we have showcased on our website so far: Mc Donald’s dollar menu Burger King value menu Be on the Lookout for Fast Food Coupons The same way you would save money at a grocery store using coupons, you can do the same when purchasing fast food.",
"Most fast food restaurants offer coupons and your job is to find them if you want to save big bucks.",
"Just to show you an example of how much of a difference a coupon can make, recently I bought 2 Jack’s Spicy Chicken sandwiches from Jack in the Box.",
"With regular price, it would have cost me over $9 with tax.",
"However, I was sneaky and pulled out a buy one Jack’s Spicy Chicken Sandwich, get one free coupon and ended up paying less than $5 with tax.",
"That means I saved almost 50% of what I would have originally spent.",
"Multiple my example above with number of times you eat at fast food restaurants per year and the savings can be quite substantial.",
"You could be saving hundreds, if not thousands of dollars each year.",
"As you can see, fast food coupons can be one of the most beneficial ways of saving money with fast food.",
"If you need help finding coupons, read our previous article about how to find fast food coupons.",
"Conclusion We just went over three great ways to save money with fast food, which includes eating in moderation, trying meals from the value menus, and using fast food coupons.",
"Do you know of another way to save money with fast food?",
"Share your thoughts in the comments.",
"Fast Food Tips Tagged eat in moderation, fast food coupons, value menus"
] |
D1039824
|
https://www.armourcard.com/rfid-blocking/
|
RFID Blocking
|
RFID Blocking only gives passive protection RFID blocking is a form of passive shielding of RFID signals through either a metallic encased wallet like Aluma Wallet or a passive lined material RFID blocking wallet or RFID blocking sleeve like most you see on the market currently. Why would you settle for passive RFID blocking or shielding^ when you can get a far superior ACTIVE countermeasure with electronic jamming technology found in every Armourcard and Armourcell Armourcard actively electronically jams the frequency these devices (credit cards & passports) communicate over (13.56MHz)RFID blocking wallets You would have seen on the market many types of RFID blocking wallets, RFID blocking sleeves and they all vary in their effectiveness^. In fact, this form of protection (passive) shielding or blocking can easily be penetrated if a criminal dial up the power on their RFID / NFC reader and its antenna output. So at the very most passive protection may limit the distance a reader could read your data and therefore not fully protect you. Armourcard is the 1st ‘Active RFID & NFC’ electronic jamming protective device. Discover Armourcard’s Active jamming technology. We personally did not want to risk our data to ‘passive blocking’At ARMOURCARD we did not want to risk our personal data being compromised by passive RFID blocking measures, so we developed and patented* ARMOURCARD, which offers Active electronic jamming RFID protection. Get on the front foot with Active RFID Protection. This means that once you place ARMOURCARD in any wallet or purse it is ready to go to protect you and your data. If someone tries to read any of your RFID enabled cards, ARMOURCARD instantly powers up and puts out a jamming signal that does not allow any data to be read from your RFID enabled Tap & Go cards, e Passports, travel cards, hotel keys, building entry keys and Identity Cards. I want to be actively protected – BUY NOW!New Micro-jamming technology stops pick pockets cold!armour card protects the RFID cards in your wallet or purse by creating an electronic Force Field. One smart card electronically protects them all.armour cell protects your cell phone. Secure your personal photos, messages, passwords, accounts and data!GET YOUR ARMOURCARD TODAYSimilar in size to your credit cards and fits right alongside them, armour card actively detects and jams out electronic thieves. If there is any doubt in your mind about security on your data, then don’t risk it!Some people will tell your that a passive shield like RFID blocking is enough to protect you, then on the other hand their are skilled hackers^ who tell us that if they dial up a more powerful RFID readers output it can penetrate passive shielding measures like RFID blocking by RFID blocking sleeves and RFID blocking wallets. Secure my identity Today!Purchase ARMOURCARD now Your Identity is worth big $$$ for criminals With identity theft big business for criminals# we did not want to leave our personal identity protection to any passive shielding devices like a RFID blocking wallet or RFID blocking sleeve. ARMOURCARD is an extra line of defence in helping you against identity theft. Start protecting yourself today Buy identity theft protection by ARMOURCARD. I want to protect my ID now!
|
[
"RFID Blocking only gives passive protection RFID blocking is a form of passive shielding of RFID signals through either a metallic encased wallet like Aluma Wallet or a passive lined material RFID blocking wallet or RFID blocking sleeve like most you see on the market currently.",
"Why would you settle for passive RFID blocking or shielding^ when you can get a far superior ACTIVE countermeasure with electronic jamming technology found in every Armourcard and Armourcell Armourcard actively electronically jams the frequency these devices (credit cards & passports) communicate over (13.56MHz)RFID blocking wallets You would have seen on the market many types of RFID blocking wallets, RFID blocking sleeves and they all vary in their effectiveness^.",
"In fact, this form of protection (passive) shielding or blocking can easily be penetrated if a criminal dial up the power on their RFID / NFC reader and its antenna output.",
"So at the very most passive protection may limit the distance a reader could read your data and therefore not fully protect you.",
"Armourcard is the 1st ‘Active RFID & NFC’ electronic jamming protective device.",
"Discover Armourcard’s Active jamming technology.",
"We personally did not want to risk our data to ‘passive blocking’At ARMOURCARD we did not want to risk our personal data being compromised by passive RFID blocking measures, so we developed and patented* ARMOURCARD, which offers Active electronic jamming RFID protection.",
"Get on the front foot with Active RFID Protection.",
"This means that once you place ARMOURCARD in any wallet or purse it is ready to go to protect you and your data.",
"If someone tries to read any of your RFID enabled cards, ARMOURCARD instantly powers up and puts out a jamming signal that does not allow any data to be read from your RFID enabled Tap & Go cards, e Passports, travel cards, hotel keys, building entry keys and Identity Cards.",
"I want to be actively protected – BUY NOW!New Micro-jamming technology stops pick pockets cold!armour card protects the RFID cards in your wallet or purse by creating an electronic Force Field.",
"One smart card electronically protects them all.armour cell protects your cell phone.",
"Secure your personal photos, messages, passwords, accounts and data!GET YOUR ARMOURCARD TODAYSimilar in size to your credit cards and fits right alongside them, armour card actively detects and jams out electronic thieves.",
"If there is any doubt in your mind about security on your data, then don’t risk it!Some people will tell your that a passive shield like RFID blocking is enough to protect you, then on the other hand their are skilled hackers^ who tell us that if they dial up a more powerful RFID readers output it can penetrate passive shielding measures like RFID blocking by RFID blocking sleeves and RFID blocking wallets.",
"Secure my identity Today!Purchase ARMOURCARD now Your Identity is worth big $$$ for criminals With identity theft big business for criminals# we did not want to leave our personal identity protection to any passive shielding devices like a RFID blocking wallet or RFID blocking sleeve.",
"ARMOURCARD is an extra line of defence in helping you against identity theft.",
"Start protecting yourself today Buy identity theft protection by ARMOURCARD.",
"I want to protect my ID now!"
] |
D2609483
|
http://www.sportsinjuryclinic.net/sport-injuries/hip-groin-pain/groin-strain/rehabilitation-of-a-groin-strain
|
Groin Strain Treatment and Rehabilitation
|
Groin Strain Treatment and Rehabilitation Jump to page Groin strains have a tendancy to recur if not treated properly. Here we outline the treatment and healing element of our groin strain rehab program. The aims of any groin strain rehabilitation program are to reducing initial pain and swelling, improve the flexibility, strengthen the muscles and gradually return to full fitness. The Sportsinjuryclinic.net rehabilitaiton plan is divided into four 'strands' of treatment, stretching, strengthening and maintaining fitness. Here we detail the treatment and healing element is broken into three phases and should be used in conjunction with our the stretching and strengthening exercises as part of our groin strain rehabilitation program. Download Groin Rehab Progress Chart Groin strains are graded 1, 2 or 3 depending on how bad they are. Where you start on the rehabilitaiton program and how fast you progress though each stage will depend on the type and extent of the injury. Phase 1 - Acute stage This phase includes from immediatly after the injury occurs until the athlete can walk pain free and has no swelling. The aim of treatment during the acute stage is to reduce pain and swelling whilst resting to allow the injury to heal. Immediate first aid - apply the PRICE princples (protection, rest, ice, compression and elevation) as soon as possible after injury, this is especially important during the first 72 hours after an injury. Protect the injured muscles by wearing a groin support, compression shorts or groin taping. This will make the injured area feel more comfortable, especially in more severe injuries. Rest from all sporting activities in the early stages of healing. If you are constantly triggering pain then you are not allowing the tissues to rest and heal. For more severe injuries use crutches if you have to walk. Apply cold therapy and compression to the area as soon as possible after injury for up to 15 minutes. Continue this at least 3 to 4 times per day. Elevate the injured limb to help swelling drain away from the site of injury. Move onto phase 2 only when walking is pain free and swelling as gone down. Phase 2 - Subacute stage Once the initial bleeding from the muscle has stopped and swelling has gone down then alternating hot and cold therapy is likely to be of more benefit. Alternate 2 minutes warm, 1 minute cold for 18 minutes. Use a hot water bottle or gel pack which can be heated along with the cold therapy and compression wrap. This can be done 2 to 3 times per day. Apply compression shorts is less important at this stage, although a groin support or heat retainer will help support the muscle as it heals. Retaining body heat encourages blood flow which aids the healing procress. A professional therapist may apply ultrasound therapy to aid the healing process, stimulate blood flow and provide a micro massage effect. Progress to stage 3 when pain free on daily activities and after a minimum of 10 days. Phase 3 - Return to full fitness This phase aims to take the athlete gradually back to full fitness and should be maintained until all stretching and strengthening exercises have been completed. The focus here is on heat to stimulate blood flow and relax the muscle fibres. Apply heat - a warm pack or hot water bottle can be applied for 20 minutes maximum at a time twice a day. Regularly monitor the skin reaction to avoid burns. This can be done as frequently as needed and in particular before stretching and strengthening exercises. A professional therapist may apply sports massage to the groin muscles. This will stimulate blood flow, soften scar tissue and iron out and tight lumps, bumps and knots in the injured tissue. Initially treatments will be light and superficial and may be applied daily. As the injury improves, deeper techniques may be used which may require a longer recovery time between treatments. Monitor sorness the day after a massage treatment. A little bit of muscle soreness is ok but too much may cause damage rather than aid the healing process. Continue with phase 3 until fully fit and all stretching and strengthening exercise levels have been completed.
|
[
"Groin Strain Treatment and Rehabilitation Jump to page Groin strains have a tendancy to recur if not treated properly.",
"Here we outline the treatment and healing element of our groin strain rehab program.",
"The aims of any groin strain rehabilitation program are to reducing initial pain and swelling, improve the flexibility, strengthen the muscles and gradually return to full fitness.",
"The Sportsinjuryclinic.net rehabilitaiton plan is divided into four 'strands' of treatment, stretching, strengthening and maintaining fitness.",
"Here we detail the treatment and healing element is broken into three phases and should be used in conjunction with our the stretching and strengthening exercises as part of our groin strain rehabilitation program.",
"Download Groin Rehab Progress Chart Groin strains are graded 1, 2 or 3 depending on how bad they are.",
"Where you start on the rehabilitaiton program and how fast you progress though each stage will depend on the type and extent of the injury.",
"Phase 1 - Acute stage This phase includes from immediatly after the injury occurs until the athlete can walk pain free and has no swelling.",
"The aim of treatment during the acute stage is to reduce pain and swelling whilst resting to allow the injury to heal.",
"Immediate first aid - apply the PRICE princples (protection, rest, ice, compression and elevation) as soon as possible after injury, this is especially important during the first 72 hours after an injury.",
"Protect the injured muscles by wearing a groin support, compression shorts or groin taping.",
"This will make the injured area feel more comfortable, especially in more severe injuries.",
"Rest from all sporting activities in the early stages of healing.",
"If you are constantly triggering pain then you are not allowing the tissues to rest and heal.",
"For more severe injuries use crutches if you have to walk.",
"Apply cold therapy and compression to the area as soon as possible after injury for up to 15 minutes.",
"Continue this at least 3 to 4 times per day.",
"Elevate the injured limb to help swelling drain away from the site of injury.",
"Move onto phase 2 only when walking is pain free and swelling as gone down.",
"Phase 2 - Subacute stage Once the initial bleeding from the muscle has stopped and swelling has gone down then alternating hot and cold therapy is likely to be of more benefit.",
"Alternate 2 minutes warm, 1 minute cold for 18 minutes.",
"Use a hot water bottle or gel pack which can be heated along with the cold therapy and compression wrap.",
"This can be done 2 to 3 times per day.",
"Apply compression shorts is less important at this stage, although a groin support or heat retainer will help support the muscle as it heals.",
"Retaining body heat encourages blood flow which aids the healing procress.",
"A professional therapist may apply ultrasound therapy to aid the healing process, stimulate blood flow and provide a micro massage effect.",
"Progress to stage 3 when pain free on daily activities and after a minimum of 10 days.",
"Phase 3 - Return to full fitness This phase aims to take the athlete gradually back to full fitness and should be maintained until all stretching and strengthening exercises have been completed.",
"The focus here is on heat to stimulate blood flow and relax the muscle fibres.",
"Apply heat - a warm pack or hot water bottle can be applied for 20 minutes maximum at a time twice a day.",
"Regularly monitor the skin reaction to avoid burns.",
"This can be done as frequently as needed and in particular before stretching and strengthening exercises.",
"A professional therapist may apply sports massage to the groin muscles.",
"This will stimulate blood flow, soften scar tissue and iron out and tight lumps, bumps and knots in the injured tissue.",
"Initially treatments will be light and superficial and may be applied daily.",
"As the injury improves, deeper techniques may be used which may require a longer recovery time between treatments.",
"Monitor sorness the day after a massage treatment.",
"A little bit of muscle soreness is ok but too much may cause damage rather than aid the healing process.",
"Continue with phase 3 until fully fit and all stretching and strengthening exercise levels have been completed."
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D423582
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https://en.wikipedia.org/wiki/Stress_hormone
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Cortisol
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"From Wikipedia, the free encyclopedia (Redirected from Stress hormone)navigation search This article is about the natural hormone. For the medication, see Hydrocortisone. Not to be confused with cortisone, a metabolite from cortisol, with a similar name, genesis, and function. This article's lead section may not adequately summarize its contents. To comply with Wikipedia's lead section guidelines, please consider modifying the lead to provide an accessible overview of the article's key points in such a way that it can stand on its own as a concise version of the article. ( discuss). (November 2016)Cortisol Names IUPAC name11β,17α,21-Trihydroxypregn-4-ene-3,20-dione Identifiers CAS Number50-23-73D model ( JSmol)Interactive image Ch EBICHEBI:17650Ch EMBLCh EMBL389621Chem Spider5551Drug Bank DB00741ECHA Info Card 100.000.019KEGGD00088Pub Chem CID5754UNIIWI4X0X7BPJIn Ch I [show]SMILES [show]Properties Chemical formula C 21 H 30 O 5Molar mass 362.460 g/mol Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 k Pa). Infobox references Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in humans by the zona fasciculata of the adrenal cortex within the adrenal gland. [1] It is released in response to stress and low blood-glucose concentration. It functions to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. [2] It also decreases bone formation. [3]Contents [ hide ]1 Health effects1.1 Metabolic response1.2 Immune response2 Other effects2.1 Metabolism2.2 Wound healing2.3 Electrolyte balance2.4 Stomach and kidneys2.5 Memory2.6 Sleep, stress, and mood2.7 Effects during pregnancy3 Synthesis and release3.1 Normal levels3.2 Disorders of cortisol production4 Regulation4.1 Factors reducing cortisol levels4.2 Factors increasing cortisol levels5 Biochemistry5.1 Biosynthesis5.2 Metabolism6 Chemistry7 Other animals8 See also9 References10 External links Health effects [ edit]Metabolic response [ edit]In the early fasting state, cortisol stimulates gluconeogenesis (the formation of glucose), and activates antistress and anti-inflammatory pathways. Cortisol also plays an important, but indirect, role in liver and muscle glycogenolysis, the breaking down of glycogen to glucose-1-phosphate and glucose. This is done through its passive influence on glucagon. [ clarification needed] Additionally, cortisol facilitates the activation of glycogen phosphorylase, which is necessary for epinephrine to have an effect on glycogenolysis. [4] [5]In the late fasting state, the function of cortisol changes slightly and increases glycogenesis. This response allows the liver to take up glucose not being used by the peripheral tissue and turn it into liver glycogen stores to be used if the body moves into the starvation state. [ citation needed]Elevated levels of cortisol, if prolonged, can lead to proteolysis (breakdown of proteins) and muscle wasting. [6] Several studies have shown that cortisol can have a lipolytic effect (promote the breakdown of fat). Under some conditions, however, cortisol may somewhat suppress lipolysis. [7]Immune response [ edit]Cortisol prevents the release of substances in the body that cause inflammation. It is used to treat conditions resulting from overactivity of the B-cell-mediated antibody response. Examples include inflammatory and rheumatoid diseases, as well as allergies. Low-potency hydrocortisone, available as a nonprescription medicine in some countries, is used to treat skin problems such as rashes and eczema. It inhibits production of interleukin (IL)-12, interferon (IFN)-gamma, IFN-alpha, and tumor-necrosis-factor (TNF)-alpha by antigen-presenting cells (APCs) and T helper (Th)1 cells, but upregulates IL-4, IL-10, and IL-13 by Th2 cells. This results in a shift toward a Th2 immune response rather than general immunosuppression. The activation of the stress system (and resulting increase in cortisol and Th2 shift) seen during an infection is believed to be a protective mechanism which prevents an over-activation of the inflammatory response. [8]Cortisol can weaken the activity of the immune system. It prevents proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor ( IL-2 ). [9] Cortisol also has a negative-feedback effect on interleukin-1. [10]Though IL-1 is useful in combating some diseases, endotoxic bacteria have gained an advantage by forcing the hypothalamus to increase cortisol levels (forcing the secretion of corticotropin-releasing hormone, thus antagonizing IL-1). The suppressor cells are not affected by glucosteroid response-modifying factor, [11] so the effective setpoint for the immune cells may be even higher than the setpoint for physiological processes (reflecting leukocyte redistribution to lymph nodes, bone marrow, and skin ). Rapid administration of corticosterone (the endogenous type I and type II receptor agonist) or RU28362 (a specific type II receptor agonist) to adrenalectomized animals induced changes in leukocyte distribution. Natural killer cells are affected by cortisol. [12]Cortisol stimulates many copper enzymes (often to 50% of their total potential), probably to increase copper availability for immune purposes. [13]: 337 This includes lysyl oxidase, an enzyme that cross-links collagen, and elastin. [13]: 334 Especially valuable for immune response is cortisol's stimulation of the superoxide dismutase, [14] since this copper enzyme is almost certainly used by the body to permit superoxides to poison bacteria. Other effects [ edit]Metabolism [ edit]Glucose [ edit]Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis [15] and inhibits the peripheral use of glucose ( insulin resistance) [15] by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane. [16] Cortisol increases blood glucose levels by increasing glycogen synthesis (glycogenesis) in the liver. [17] The permissive effect of cortisol on insulin action in liver glycogenesis is observed in hepatocyte culture in the laboratory, although the mechanism for this is unknown. Bone and collagen [ edit]Cortisol reduces bone formation, [3] favoring long-term development of osteoporosis (progressive bone disease). It transports potassium out of cells in exchange for an equal number of sodium ions (see above). [18] This can trigger the hyperkalemia of metabolic shock from surgery. Cortisol also reduces calcium absorption in the intestine. [19]Collagen is an important component of connective tissue. It is vital for structural support and is found in muscles, tendons, and joints, as well as throughout the entire body. Cortisol down-regulates the synthesis of collagen. [20]Amino acid [ edit]Cortisol raises the free amino acids in the serum by inhibiting collagen formation, decreasing amino acid uptake by muscle, and inhibiting protein synthesis. [21] Cortisol (as opticortinol) may inversely inhibit Ig A precursor cells in the intestines of calves. [22] Cortisol also inhibits Ig A in serum, as it does Ig M; however, it is not shown to inhibit Ig E. [23]Wound healing [ edit]Cortisol and the stress response have known deleterious effects on the immune system. High levels of perceived stress and increases in cortisol have been found to lengthen wound-healing time in healthy, male adults. Those who had the lowest levels of cortisol the day following a 4 mm punch biopsy had the fastest healing time. [24] In dental students, wounds from punch biopsies took an average of 40% longer to heal when performed three days before an examination as opposed to biopsies performed on the same students during summer vacation. [25] This is in line with previous animal studies that show similar detrimental effects on wound healing, notably the primary reports showing that turtles recoil from cortisol. [26]Electrolyte balance [ edit]Cortisol acts as a diuretic, increasing water diuresis, glomerular filtration rate, and renal plasma flow from the kidneys, as well as increasing sodium retention and potassium excretion. It also increases sodium and water absorption and potassium excretion in the intestines. [27]Sodium [ edit]Cortisol promotes sodium absorption through the small intestine of mammals. [28] Sodium depletion, however, does not affect cortisol levels [29] so cortisol cannot be used to regulate serum sodium. Cortisol's original purpose may have been sodium transport. This hypothesis is supported by the fact that freshwater fish use cortisol to stimulate sodium inward, while saltwater fish have a cortisol-based system for expelling excess sodium. [30]Potassium [ edit]A sodium load augments the intense potassium excretion by cortisol. Corticosterone is comparable to cortisol in this case. [31] For potassium to move out of the cell, cortisol moves an equal number of sodium ions into the cell. [18] This should make p H regulation much easier (unlike the normal potassium-deficiency situation, in which two sodium ions move in for each three potassium ions that move out—closer to the deoxycorticosterone effect). Stomach and kidneys [ edit]Cortisol stimulates gastric-acid secretion. [32] Cortisol's only direct effect on the hydrogen-ion excretion of the kidneys is to stimulate the excretion of ammonium ions by deactivating the renal glutaminase enzyme. [33]Memory [ edit]Cortisol works with epinephrine (adrenaline) to create memories of short-term emotional events; this is the proposed mechanism for storage of flash-bulb memories, and may originate as a means to remember what to avoid in the future. [34] However, long-term exposure to cortisol damages cells in the hippocampus; [35] this damage results in impaired learning. Furthermore, cortisol inhibits memory retrieval of already stored information. [36] [37]Sleep, stress, and mood [ edit]Diurnal cycles of cortisol levels are found in humans. [4] In humans, the amount of cortisol present in the blood undergoes diurnal variation; the level peaks in the early morning (around 8 am) and reaches its lowest level at about midnight-4 am, or three to five hours after the onset of sleep. Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. This pattern is not present at birth; estimates of when it begins vary from two weeks to nine months of age. [38]Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, mood disorders such as major depressive disorder, anxiety disorders, psychological stress, and physiological stressors such as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion, or temperature extremes. Cortisol levels may also differ for individuals with autism or Asperger's syndrome. [39] Also, significant individual variation is seen, although a given person tends to have consistent rhythms. Effects during pregnancy [ edit]During human pregnancy, increased fetal production of cortisol between weeks 30 and 32 initiates production of fetal lung surfactant to promote maturation of the lungs. In fetal lambs, glucocorticoids (principally cortisol) increase after about day 130, with lung surfactant increasing greatly, in response, by about day 135, [40] and although lamb fetal cortisol is mostly of maternal origin during the first 122 days, 88% or more is of fetal origin by day 136 of gestation. [41] Although the timing of fetal cortisol concentration elevation in sheep may vary somewhat, it averages about 11.8 days before the onset of labor. [42] In several livestock species (e.g. cattle, sheep, goats, and pigs), the surge of fetal cortisol late in gestation triggers the onset of parturition by removing the progesterone block of cervical dilation and myometrial contraction. The mechanisms yielding this effect on progesterone differ among species. In the sheep, where progesterone sufficient for maintaining pregnancy is produced by the placenta after about day 70 of gestation, [43] [44] the prepartum fetal cortisol surge induces placental enzymatic conversion of progesterone to estrogen. (The elevated level of estrogen stimulates prostaglandin secretion and oxytocin receptor development. )Exposure of fetuses to cortisol during gestation can have a variety of developmental outcomes, including alterations in prenatal and postnatal growth patterns. In marmosets, a species of New World primates, pregnant females have varying levels of cortisol during gestation, both within and between females. Infants born to mothers with high gestational cortisol during the first trimester of pregnancy had lower rates of growth in body mass indices than infants born to mothers with low gestational cortisol (about 20% lower). However, postnatal growth rates in these high-cortisol infants was more rapid than low-cortisol infants later in postnatal periods, and complete catch-up in growth had occurred by 540 days of age. These results suggest that gestational exposure to cortisol in fetuses has important potential fetal programming effects on both pre- and postnatal growth in primates. [45]Synthesis and release [ edit]Cortisol is produced in the human body by the adrenal gland in the zona fasciculata, [1] the second of three layers comprising the adrenal cortex. The cortex forms the outer ""bark"" of each adrenal gland, situated atop the kidneys. The release of cortisol is controlled by the hypothalamus, a part of the brain. The secretion of corticotropin-releasing hormone by the hypothalamus [46] triggers cells in the neighboring anterior pituitary to secrete another hormone, the adrenocorticotropic hormone (ACTH), into the vascular system, through which blood carries it to the adrenal cortex. ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids, and dehydroepiandrosterone. Normal levels [ edit]Normal values indicated in the following tables pertain to humans (normal levels vary among species). Measured cortisol levels, and therefore reference ranges, depend on the analytical method used and factors such as age and sex. Test results should, therefore, always be interpreted using the reference range from the laboratory that produced the result. Reference ranges for blood plasma content of free cortisol Time Lower limit Upper limit Unit09:00 am 140 [47] 700 [47] nmol/L5 [48] 25 [48] μg/d LMidnight 80 [47] 350 [47] nmol/l2.9 [48] 13 [48] μg/dl Using the molecular weight of 362.460 g/mole, the conversion factor from µg/dl to nmol/l is approximately 27.6; thus, 10 µg/dl is about 276 nmol/l. Reference ranges for urinalysis of free cortisol Lower limit Upper limit Unit28 [49] or 30 [50] 280 [49] or 490 [50] nmol /24h10 [51] or 11 [52] 100 [51] or 176 [52] µg /24 h Disorders of cortisol production [ edit]Cushing's syndrome or hypercortisolism: Excessive levels of cortisol in the blood Hypocortisolism: Insufficient levels of cortisol in the blood Disorders of cortisol production, and some consequent conditions, are: Primary hypercortisolism (Cushing's syndrome)Primary hypocortisolism ( Addison's disease, Nelson's syndrome )Secondary hypercortisolism (pituitary tumor resulting in Cushing's disease, [53] [54] pseudo-Cushing's syndrome)Secondary hypocortisolism (pituitary tumor, Sheehan's syndrome)Regulation [ edit]The primary control of cortisol is the pituitary gland peptide, ACTH, which probably controls cortisol by controlling the movement of calcium into the cortisol-secreting target cells. [55] ACTH is in turn controlled by the hypothalamic peptide corticotropin-releasing hormone (CRH), which is under nervous control. CRH acts synergistically with arginine vasopressin, angiotensin II, and epinephrine. [56] (In swine, which do not produce arginine vasopressin, lysine vasopressin acts synergistically with CRH. [57])When activated macrophages start to secrete IL-1, which synergistically with CRH increases ACTH, [10] T-cells also secrete glucosteroid response modifying factor (GRMF), as well as IL-1; both increase the amount of cortisol required to inhibit almost all the immune cells. [11] Immune cells then assume their own regulation, but at a higher cortisol setpoint. The increase in cortisol in diarrheic calves is minimal over healthy calves, however, and falls over time. [58] The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a negative feedback effect on interleukin-1 [10] —especially useful to treat diseases that force the hypothalamus to secrete too much CRH, such as those caused by endotoxic bacteria. The suppressor immune cells are not affected by GRMF, [11] so the immune cells' effective setpoint may be even higher than the setpoint for physiological processes. GRMF affects primarily the liver (rather than the kidneys) for some physiological processes. [59]High-potassium media (which stimulates aldosterone secretion in vitro) also stimulate cortisol secretion from the fasciculata zone of canine adrenals [60] [61] — unlike corticosterone, upon which potassium has no effect. [62]Potassium loading also increases ACTH and cortisol in humans. [63] This is probably the reason why potassium deficiency causes cortisol to decline (as mentioned) and causes a decrease in conversion of 11-deoxycortisol to cortisol. [64] This may also have a role in rheumatoid-arthritis pain; cell potassium is always low in RA. [65]Ascorbic acid presence, particularly in high doses has also been shown to mediate response to psychological stress and speed the decrease of the levels of circulating cortisol in the body post stress. This can be evidenced through a decrease in systolic and diastolic blood pressures and decreased salivary cortisol level after treatment with ascorbic acid. [66]Factors reducing cortisol levels [ edit]Magnesium supplementation decreases serum cortisol levels after aerobic exercise, [67] [68] but not after resistance training. [69]Omega-3 fatty acids have a dose-dependent effect [70] in slightly reducing cortisol release influenced by mental stress, [71] suppressing the synthesis of interleukin -1 and -6 and enhancing the synthesis of interleukin-2; the former promotes higher CRH release. Omega-6 fatty acids, though, have an inverse effect on interleukin synthesis. [72]Music therapy can reduce cortisol levels in certain situations. [73]Massage therapy can reduce cortisol. [74]Laughing, and the experience of humor, can lower cortisol levels. [75]Soy-derived phosphatidylserine interacts with cortisol; the correct dose, however, is unclear. [76] [77] [78] [79]Regular dancing has been shown to lead to significant decreases in salivary cortisol concentrations. [80]Withania somnifera (ashwagandha) root extract [81]High-dosage treatment with ascorbic acid (vitamin C) has been shown to decrease circulating cortisol levels during and shortly after the treatment period. [66]Factors increasing cortisol levels [ edit]Viral infections increase cortisol levels through activation of the HPA axis by cytokines. [82]Caffeine may increase cortisol levels. [83]Sleep deprivation [84]Intense (high VO 2max) or prolonged aerobic exercise transiently increases cortisol levels to increase gluconeogenesis and maintain blood glucose; [85] however, cortisol declines to normal levels after eating (i.e., restoring a neutral energy balance) [86]The Val/Val variation of the BDNF gene in men and the Val/Met variation in women are associated with increased salivary cortisol in a stressful situation. [87]Severe trauma or stressful events can elevate cortisol levels in the blood for prolonged periods. [88]Subcutaneous adipose tissue regenerates cortisol from cortisone by the enzyme 11-beta HSD1. [89]Anorexia nervosa may be associated with increased cortisol levels. [90]The serotonin receptor gene 5HTR2C is associated with increased cortisol production in men. [91]Smelling androstadienone has been found in one study to raise cortisol levels in women, as well as, in other studies, to affect mood (see androstadienone article for details and citations). Excessive or problematic drinking has been linked to increased cortisol levels, especially in college students. [92]Biochemistry [ edit]Biosynthesis [ edit]Steroidogenesis, showing cortisol at right. [93]Cortisol is synthesized from cholesterol. Synthesis takes place in the zona fasciculata of the adrenal cortex. (The name cortisol is derived from cortex.) While the adrenal cortex also produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticularis), cortisol is its main secretion in humans and several other species. (However, in cattle, corticosterone levels may approach [94] or exceed [4] cortisol levels.). The medulla of the adrenal gland lies under the cortex, mainly secreting the catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation. The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with ACTH; ACTH production is, in turn, stimulated by CRH, which is released by the hypothalamus. ACTH increases the concentration of cholesterol in the inner mitochondrial membrane, via regulation of the steroidogenic acute regulatory protein. It also stimulates the main rate-limiting step in cortisol synthesis, in which cholesterol is converted to pregnenolone and catalyzed by cytochrome P450SCC ( side-chain cleavage enzyme ). [95]Metabolism [ edit]Cortisol is metabolized by the 11-beta hydroxysteroid dehydrogenase system (11-beta HSD), which consists of two enzymes: 11-beta HSD1 and 11-beta HSD2.11-beta HSD1 uses the cofactor NADPH to convert biologically inert cortisone to biologically active cortisol11-beta HSD2 uses the cofactor NAD+ to convert cortisol to cortisone Overall, the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue; 11-beta HSD2 serves to decrease local concentrations of biologically active cortisol. Cortisol is also metabolized into 5-alpha tetrahydrocortisol (5-alpha THF) and 5-beta tetrahydrocortisol (5-beta THF), reactions for which 5-alpha reductase and 5-beta reductase are the rate-limiting factors, respectively. 5-Beta reductase is also the rate-limiting factor in the conversion of cortisone to tetrahydrocortisone. An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis of obesity, hypertension, and insulin resistance known as metabolic syndrome. [96]An alteration in 11-beta HSD2 has been implicated in essential hypertension and is known to lead to the syndrome of apparent mineralocorticoid excess (SAME). Chemistry [ edit]Cortisol is a naturally occurring pregnane corticosteroid and is also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione. Other animals [ edit]In non-human animals, cortisol is often used as an indicator of stress and can be measured in blood, [97] saliva, [98] urine, [99] hair, [100] and faeces. [100] [101]See also [ edit]Cortisone, a hormone Membrane glucocorticoid receptor List of corticosteroids References [ edit]^ a b Scott E (2011-09-22). ""Cortisol and Stress: How to Stay Healthy"". About.com. Retrieved 2011-11-29. [ better source needed]^ Hoehn K, Marieb EN (2010). Human Anatomy & Physiology. San Francisco: Benjamin Cummings. ISBN 0-321-60261-7.^ a b Chyun YS, Kream BE, Raisz LG (February 1984). ""Cortisol decreases bone formation by inhibiting periosteal cell proliferation"". Endocrinology. 114 (2): 477–80. doi: 10.1210/endo-114-2-477. PMID 6690287.^ a b c Martin PA, Crump MH (2003). ""The adrenal gland"". In Dooley MP, Pineda MH. Mc Donald's veterinary endocrinology and reproduction (5th ed.). Ames, Iowa: Iowa State Press. ISBN 0-8138-1106-6.^ Coderre L, Srivastava AK, Chiasson JL (June 1991). ""Role of glucocorticoid in the regulation of glycogen metabolism in skeletal muscle"". The American Journal of Physiology. 260 (6 Pt 1): E927–32. PMID 1905485.^ Simmons PS, Miles JM, Gerich JE, Haymond MW (February 1984). ""Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range"". The Journal of Clinical Investigation. 73 (2): 412–20. doi: 10.1172/JCI111227. PMC 425032. PMID 6365973.^ Djurhuus CB, Gravholt CH, Nielsen S, Mengel A, Christiansen JS, Schmitz OE, Møller N (July 2002). ""Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans"". American Journal of Physiology. Endocrinology and Metabolism. 283 (1): E172–7. doi: 10.1152/ajpendo.00544.2001. PMID 12067858.^ Elenkov IJ (June 2004). ""Glucocorticoids and the Th1/Th2 balance"". Annals of the New York Academy of Sciences. 1024 (1): 138–46. Bibcode: 2004NYASA1024..138E. doi: 10.1196/annals.1321.010. PMID 15265778.^ Palacios R, Sugawara I (January 1982). ""Hydrocortisone abrogates proliferation of T cells in autologous mixed lymphocyte reaction by rendering the interleukin-2 Producer T cells unresponsive to interleukin-1 and unable to synthesize the T-cell growth factor"". Scandinavian Journal of Immunology. 15 (1): 25–31. doi: 10.1111/j.1365-3083.1982.tb00618.x. PMID 6461917.^ a b c Besedovsky HO, Del Rey A, Sorkin E (1986). ""Integration of Activated Immune Cell Products in Immune Endocrine Feedback Circuits"". In Oppenheim JJ, Jacobs DM. Leukocytes and Host Defense. Progress in Leukocyte Biology. 5. New York: Alan R. Liss. p. 200.^ a b c Fairchild SS, Shannon K, Kwan E, Mishell RI (February 1984). ""T cell-derived glucosteroid response-modifying factor (GRMFT): a unique lymphokine made by normal T lymphocytes and a T cell hybridoma"". Journal of Immunology. 132 (2): 821–7. PMID 6228602.^ Mavoungou E, Bouyou-Akotet MK, Kremsner PG (February 2005). ""Effects of prolactin and cortisol on natural killer (NK) cell surface expression and function of human natural cytotoxicity receptors (NKp46, NKp44 and NKp30)"". Clinical and Experimental Immunology. 139 (2): 287–96. doi: 10.1111/j.1365-2249.2004.02686.x. PMC 1809301. PMID 15654827.^ a b Weber CE (December 1984). ""Copper response to rheumatoid arthritis"". Medical Hypotheses. 15 (4): 333–48. doi: 10.1016/0306-9877 (84)90150-6. PMID 6152006.^ Flohe L, Beckman R, Giertz H, Loschen G (1985). ""Oxygen Centered Free Radicals as Mediators of Inflammation"". In Sies H. Oxidative stress. London: Orlando. p. 405. ISBN 0-12-642760-7.^ a b Brown DF, Brown DD (2003). USMLE Step 1 Secrets: Questions You Will Be Asked on USMLE Step 1. Philadelphia: Hanley & Belfus. p. 63. ISBN 1-56053-570-9. [ better source needed]^ King MB (2005). Lange Q & A. New York: Mc Graw-Hill, Medical Pub. Division. ISBN 0-07-144578-1.^ Baynes J, Dominiczak M (2009). Medical biochemistry. Mosby Elsevier. ISBN 0-323-05371-8.^ a b Knight RP, Kornfeld DS, Glaser GH, Bondy PK (February 1955). ""Effects of intravenous hydrocortisone on electrolytes of serum and urine in man"". The Journal of Clinical Endocrinology and Metabolism. 15 (2): 176–81. doi: 10.1210/jcem-15-2-176. PMID 13233328.^ Deutsch E (April 1978). "" [Pathogenesis of thrombocytopenia. 2. Distribution disorders, pseudo-thrombocytopenias]"". Fortschritte Der Medizin (in German). 96 (14): 761–2. PMID 346457.^ Kucharz EJ (1988). ""Hormonal control of collagen metabolism. Part II"". Endocrinologie. 26 (4): 229–37. PMID 3062759.^ Manchester, KL (1964). ""Sites of Hormonal Regulation of Protein Metabolism"". In Allison, NH & Munro JB. Mammalian Protein Metabolism. New York: Academic Press. p. 229? 273?.^ Husband AJ, Brandon MR, Lascelles AK (October 1973). ""The effect of corticosteroid on absorption and endogenous production of immunoglobulins in calves"". The Australian Journal of Experimental Biology and Medical Science. 51 (5): 707–10. doi: 10.1038/icb.1973.67. PMID 4207041.^ Posey WC, Nelson HS, Branch B, Pearlman DS (December 1978). ""The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels"". The Journal of Allergy and Clinical Immunology. 62 (6): 340–8. doi: 10.1016/0091-6749 (78)90134-3. PMID 712020.^ Ebrecht M, Hextall J, Kirtley LG, Taylor A, Dyson M, Weinman J (July 2004). ""Perceived stress and cortisol levels predict speed of wound healing in healthy male adults"". Psychoneuroendocrinology. 29 (6): 798–809. doi: 10.1016/s0306-4530 (03)00144-6. PMID 15110929.^ Marucha PT, Kiecolt-Glaser JK, Favagehi M (1998). ""Mucosal wound healing is impaired by examination stress"". Psychosomatic Medicine. 60 (3): 362–5. doi: 10.1097/00006842-199805000-00025. PMID 9625226.^ Zhou X, Xie M, Niu C, Sun R (June 2003). ""The effects of dietary vitamin C on growth, liver vitamin C and serum cortisol in stressed and unstressed juvenile soft-shelled turtles (Pelodiscus sinensis)"". Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. 135 (2): 263–70. doi: 10.1016/s1095-6433 (03)00066-7. PMID 12781826.^ Mc Kay LI, Cidlowski JA (2003). ""Physiologic and Pharmacologic Effects of Corticosteroids"". In Kure DW, Pollock RE, Weichselbaum RR, Bast RC, Ganglier TS, Holland JF, Frei E. Holland-Frei Cancer Medicine (6 ed.). Hamilton, Ontario: Decker. ISBN 978-1-55009-213-4.^ Sandle GI, Keir MJ, Record CO (1981). ""The effect of hydrocortisone on the transport of water, sodium, and glucose in the jejunum. Perfusion studies in normal subjects and patients with coeliac disease"". Scandinavian Journal of Gastroenterology. 16 (5): 667–71. doi: 10.3109/00365528109182028. PMID 7323700.^ Mason PA, Fraser R, Morton JJ, Semple PF, Wilson A (August 1977). ""The effect of sodium deprivation and of angiotensin II infusion on the peripheral plasma concentrations of 18-hydroxycorticosterone, aldosterone and other corticosteroids in man"". Journal of Steroid Biochemistry. 8 (8): 799–804. doi: 10.1016/0022-4731 (77)90086-3. PMID 592808.^ Gorbman A, Dickhoff WW, Vigna SR, Clark NB, Muller AF (1983). Comparative endocrinology. New York: Wiley. ISBN 0-471-06266-9.^ Muller AF, Oconnor CM (1958). An International Symposium on Aldosterone. Little Brown & Co. p. 58.^ Soffer LJ, Dorfman RI, Gabrilove JL (1961). The Human Adrenal Gland. Philadelphia: Lea & Febiger.^ Kokoshchuk GI, Pakhmurnyĭ BA (May 1979). "" [Role of glucocorticoids in regulating the acid-excreting function of the kidneys]"". Fiziologicheskii Zhurnal SSSR Imeni I. M. Sechenova. 65 (5): 751–4. PMID 110627.^ Kennedy, Ron. ""Cortisol (Hydrocortisone)"". The Doctors' Medical Library. Retrieved 14 June 2013.^ Mc Auley MT, Kenny RA, Kirkwood TB, Wilkinson DJ, Jones JJ, Miller VM (March 2009). ""A mathematical model of aging-related and cortisol induced hippocampal dysfunction"". BMC Neuroscience. 10: 26. doi: 10.1186/1471-2202-10-26. PMC 2680862. PMID 19320982.^ de Quervain DJ, Roozendaal B, Mc Gaugh JL (August 1998). ""Stress and glucocorticoids impair retrieval of long-term spatial memory"". Nature. 394 (6695): 787–90. Bibcode: 1998Natur.394..787D. doi: 10.1038/29542. PMID 9723618.^ de Quervain DJ, Roozendaal B, Nitsch RM, Mc Gaugh JL, Hock C (April 2000). ""Acute cortisone administration impairs retrieval of long-term declarative memory in humans"". Nature Neuroscience. 3 (4): 313–4. doi: 10.1038/73873. PMID 10725918.^ de Weerth C, Zijl RH, Buitelaar JK (August 2003). ""Development of cortisol circadian rhythm in infancy"". Early Human Development. 73 (1–2): 39–52. doi: 10.1016/S0378-3782 (03)00074-4. PMID 12932892.^ ""Asperger's stress hormone 'link ' "". BBC News Online. 2009-04-02. Retrieved 2010-04-30.^ Mescher EJ, Platzker AC, Ballard PL, Kitterman JA, Clements JA, Tooley WH (December 1975). ""Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb"". Journal of Applied Physiology. 39 (6): 1017–21. PMID 2573.^ Hennessy DP, Coghlan JP, Hardy KJ, Scoggins BA, Wintour EM (October 1982). ""The origin of cortisol in the blood of fetal sheep"". The Journal of Endocrinology. 95 (1): 71–9. doi: 10.1677/joe.0.0950071. PMID 7130892.^ Magyar DM, Fridshal D, Elsner CW, Glatz T, Eliot J, Klein AH, Lowe KC, Buster JE, Nathanielsz PW (July 1980). ""Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition"". Endocrinology. 107 (1): 155–9. doi: 10.1210/endo-107-1-155. PMID 7379742.^ Ricketts AP, Flint AP (August 1980). ""Onset of synthesis of progesterone by ovine placenta"". The Journal of Endocrinology. 86 (2): 337–47. doi: 10.1677/joe.0.0860337. PMID 6933207.^ Al-Gubory KH, Solari A, Mirman B (1999). ""Effects of luteectomy on the maintenance of pregnancy, circulating progesterone concentrations and lambing performance in sheep"". Reproduction, Fertility, and Development. 11 (6): 317–22. doi: 10.1071/RD99079. PMID 10972299.^ Mustoe AC, Birnie AK, Korgan AC, Santo JB, French JA (February 2012). ""Natural variation in gestational cortisol is associated with patterns of growth in marmoset monkeys (Callithrix geoffroyi)"". General and Comparative Endocrinology. 175 (3): 519–26. doi: 10.1016/j.ygcen.2011.12.020. PMC 3268124. PMID 22212825.^ ""You & Your Hormones : Cortisol"". the Society for Endocrinology (Last updated) :. October 24, 2013. Archived from the original on November 24, 2014. Retrieved November 24, 2014.^ a b c d Biochemistry Reference Ranges at Good Hope Hospital Retrieved 8 November 2009 [ better source needed]^ a b c d Derived from molar values using molar mass of 362 g/mol^ a b Converted from µg/24h, using molar mass of 362.460 g/mol^ a b Görges R, Knappe G, Gerl H, Ventz M, Stahl F (April 1999). ""Diagnosis of Cushing's syndrome: re-evaluation of midnight plasma cortisol vs urinary free cortisol and low-dose dexamethasone suppression test in a large patient group"". Journal of Endocrinological Investigation. 22 (4): 241–9. doi: 10.1007/bf03343551. PMID 10342356.^ a b Medline Plus Encyclopedia Cortisol – urine^ a b Converted from nmol/24h, using molar mass of 362.460 g/mol^ ""Cushing's Syndrome"". National Endocrine and Metabolic Diseases Information Service (NEMDIS). July 2008. Retrieved 16 March 2015. These benign, or noncancerous, tumors of the pituitary gland secrete extra ACTH. Most people with the disorder have a single adenoma. This form of the syndrome, known as Cushing's disease^ Forbis P (2005). Stedman's medical eponyms (2nd ed.). Baltimore, Md. : Lippincott Williams & Wilkins. p. 167. ISBN 978-0-7817-5443-9.^ Davies E, Kenyon CJ, Fraser R (June 1985). ""The role of calcium ions in the mechanism of ACTH stimulation of cortisol synthesis"". Steroids. 45 (6): 551–60. doi: 10.1016/0039-128X (85)90019-4. PMID 3012830.^ Plotsky PM, Otto S, Sapolsky RM (September 1986). ""Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback"". Endocrinology. 119 (3): 1126–30. doi: 10.1210/endo-119-3-1126. PMID 3015567.^ Minton JE, Parsons KM (March 1993). ""Adrenocorticotropic hormone and cortisol response to corticotropin-releasing factor and lysine vasopressin in pigs"". Journal of Animal Science. 71 (3): 724–9. PMID 8385088.^ Dvorak M (1971). ""Plasma 17-Hydroxycorticosteroid Levels in Healthy and Diarrheic Calves"". British Veterinarian Journal. 127: 372.^ Stith RD, Mc Callum RE (1986). ""General effect of endotoxin on glucocorticoid receptors in mammalian tissues"". Circulatory Shock. 18 (4): 301–9. PMID 3084123.^ Mikosha AS, Pushkarov IS, Chelnakova IS, Remennikov GY (1991). ""Potassium Aided Regulation of Hormone Biosynthesis in Adrenals of Guinea Pigs Under Action of Dihydropyridines: Possible Mechanisms of Changes in Steroidogenesis Induced by 1,4, Dihydropyridines in Dispersed Adrenocorticytes"". Fiziol. [Kiev]. 37: 60.^ ""Ameer Saadallah Al – Zacko"" (PDF). Retrieved 11 July 2013.^ Mendelsohn FA, Mackie C (July 1975). ""Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells"". Clinical Science and Molecular Medicine. 49 (1): 13–26. doi: 10.1042/cs0490013. PMID 168026.^ Ueda Y, Honda M, Tsuchiya M, Watanabe H, Izumi Y, Shiratsuchi T, Inoue T, Hatano M (April 1982). ""Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension"". Japanese Circulation Journal. 46 (4): 317–22. doi: 10.1253/jcj.46.317. PMID 6283190.^ Bauman K, Muller J (1972). ""Effect of potassium on the final status of aldosterone biosynthesis in the rat. I 18-hydroxylation and 18hydroxy dehydrogenation. II beta-hydroxylation"". Acta Endocrin. Copenh. 69: I 701–717, II 718–730.^ La Celle PL, Morgan ES, Atwater EC (1964). ""An investigation of total body potassium in patients with rheumatoid arthritis"". Proceedings of the Annual Meeting of the American Rheumatism Association, Arthritis and Rheumatism. 7 (3): 321.^ a b Brody S, Preut R, Schommer K, Schürmeyer TH (January 2002). ""A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress"". Psychopharmacology. 159 (3): 319–24. doi: 10.1007/s00213-001-0929-6. PMID 11862365.^ Golf SW, Happel O, Graef V, Seim KE (November 1984). ""Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation"". Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift für Klinische Chemie Und Klinische Biochemie. 22 (11): 717–21. doi: 10.1515/cclm.1984.22.11.717. PMID 6527092.^ Golf SW, Bender S, Grüttner J (September 1998). ""On the significance of magnesium in extreme physical stress"". Cardiovascular Drugs and Therapy. 12 Suppl 2 (2suppl): 197–202. doi: 10.1023/A:1007708918683. PMID 9794094.^ Wilborn CD, Kerksick CM, Campbell BI, Taylor LW, Marcello BM, Rasmussen CJ, Greenwood MC, Almada A, Kreider RB (December 2004). ""Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism"". Journal of the International Society of Sports Nutrition. 1 (2): 12–20. doi: 10.1186/1550-2783-1-2-12. PMC 2129161. PMID 18500945.^ Bhathena SJ, Berlin E, Judd JT, Kim YC, Law JS, Bhagavan HN, Ballard-Barbash R, Nair PP (October 1991). ""Effects of omega 3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men"". The American Journal of Clinical Nutrition. 54 (4): 684–8. PMID 1832814.^ Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L (June 2003). ""Fish oil prevents the adrenal activation elicited by mental stress in healthy men"". Diabetes & Metabolism. 29 (3): 289–95. doi: 10.1016/S1262-3636 (07)70039-3. PMID 12909818.^ Yehuda S (2003). ""Omega-6/omega-3 ratio brain related functions"". In Simopoulos AP, Cleland LG. Omega-6, omega-3 essential fatty acid ratio: the scientific evidence. Basel: Karger. p. 50. ISBN 3-8055-7640-4.^ Uedo N, Ishikawa H, Morimoto K, Ishihara R, Narahara H, Akedo I, Ioka T, Kaji I, Fukuda S (2004). ""Reduction in salivary cortisol level by music therapy during colonoscopic examination"". Hepato-Gastroenterology. 51 (56): 451–3. PMID 15086180.^ Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C (October 2005). ""Cortisol decreases and serotonin and dopamine increase following massage therapy"". The International Journal of Neuroscience. 115 (10): 1397–413. doi: 10.1080/00207450590956459. PMID 16162447.^ Berk LS, Tan SA, Berk D (2008). ""Cortisol and Catecholamine stress hormone decrease is associated with the behavior of perceptual anticipation of mirthful laughter"". The FASEB Journal. 22 (1): 946.11.^ Hellhammer J, Fries E, Buss C, Engert V, Tuch A, Rutenberg D, Hellhammer D (June 2004). ""Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress"". Stress. 7 (2): 119–26. doi: 10.1080/10253890410001728379. PMID 15512856.^ Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R (July 2008). ""The effects of phosphatidylserine on endocrine response to moderate intensity exercise"". Journal of the International Society of Sports Nutrition. 5: 11. doi: 10.1186/1550-2783-5-11. PMC 2503954. PMID 18662395.^ Steptoe A, Gibson EL, Vuononvirta R, Williams ED, Hamer M, Rycroft JA, Erusalimsky JD, Wardle J (January 2007). ""The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial"". Psychopharmacology. 190 (1): 81–9. doi: 10.1007/s00213-006-0573-2. PMID 17013636.^ ""medicalnewstoday"". Retrieved 25 September 2013.^ Quiroga MC, Bongard S, Kreutz G (July 2009). ""Emotional and Neurohumoral Responses to Dancing Tango Argentino: The Effects of Music and Partner"". Music and Medicine. 1 (1): 14–21. doi: 10.1177/1943862109335064.^ Chandrasekhar K, Kapoor J, Anishetty S (July 2012). ""A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults"". Indian Journal of Psychological Medicine. 34 (3): 255–62. doi: 10.4103/0253-7176.106022. PMC 3573577. PMID 23439798.^ Silverman MN, Pearce BD, Biron CA, Miller AH (2005). ""Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection"". Viral Immunology. 18 (1): 41–78. doi: 10.1089/vim.2005.18.41. PMC 1224723. PMID 15802953.^ Lovallo WR, Farag NH, Vincent AS, Thomas TL, Wilson MF (March 2006). ""Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women"". Pharmacology Biochemistry and Behavior. 83 (3): 441–7. doi: 10.1016/j.pbb.2006.03.005. PMC 2249754. PMID 16631247.^ Leproult R, Copinschi G, Buxton O, Van Cauter E (October 1997). ""Sleep loss results in an elevation of cortisol levels the next evening"". Sleep. 20 (10): 865–70. PMID 9415946.^ Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M (February 1999). ""Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes"". International Journal of Sports Medicine. 20 (2): 128–35. doi: 10.1055/s-2007-971106. PMID 10190775.^ Fuqua JS, Rogol AD (July 2013). ""Neuroendocrine alterations in the exercising human: implications for energy homeostasis"". Metabolism. 62 (7): 911–21. doi: 10.1016/j.metabol.2013.01.016. PMID 23415825. Cortisol has wide-ranging effects, including alterations of carbohydrate, protein, and lipid metabolism; catabolic effects on skin, muscle, connective tissue, and bone; immunomodulatory effects; blood pressure and circulatory system regulation; and effects on mood and central nervous system function. In the short term, activation of the HPA axis in response to stress is adaptive. However, long-term stress promoting chronic exposure of tissues to high cortisol concentrations becomes maladaptive. ... Exercise, particularly sustained aerobic activity, is a potent stimulus of cortisol secretion. The circulating concentrations of cortisol are directly proportional to the intensity of exercise as measured by oxygen uptake. As is the case for the GH/IGF-1 and HPG axes, the HPA axis also receives many other inputs, including the light/dark cycle, feeding schedules, immune regulation, and many neurotransmitters that mediate the effects of exercise and physical and psychic stress [52]. ... The HPA is activated by stress, whether physical (exercise) or psychological. Increased cortisol production, along with activation of the sympathetic nervous system, affects whole body metabolism. This is apparently part of the catabolic response of the entire organism, with the purpose of mobilizing metabolic fuels that are subsequently broken down to produce energy and to dampen the threat or perceived threat. ... Thus, a negative net energy balance leads to activation of the HPA axis and the circulating concomitants of the catabolic state in an attempt to keep core processes functional, realizing that the stress of exercise has no effect on cortisol and circulating metabolic substrates beyond the impact of the exercise energy expenditure on energy availability [60]. Thuma et al. [61] had already made the important observation that the reported differences in cortisol levels pre- and postexercise depended on whether this difference was measured from a single pretest level or from the physiologic circadian baseline as determined in an independent session in the resting state. By this analytical technique, these investigators showed that increasing energy expenditure led to significant cortisol release. This release was apparent if they subtracted the physiologic circadian baseline from the postexercise value.^ Shalev I, Lerer E, Israel S, Uzefovsky F, Gritsenko I, Mankuta D, Ebstein RP, Kaitz M (April 2009). ""BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions"". Psychoneuroendocrinology. 34 (3): 382–8. doi: 10.1016/j.psyneuen.2008.09.017. PMID 18990498.^ Smith JL, Gropper SA, Groff JL (2009). Advanced nutrition and humanmetabolism. Belmont, CA: Wadsworth Cengage Learning. p. 247. ISBN 0-495-11657-2.^ Stimson RH, Andersson J, Andrew R, Redhead DN, Karpe F, Hayes PC, Olsson T, Walker BR (January 2009). ""Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans"". Diabetes. 58 (1): 46–53. doi: 10.2337/db08-0969. PMC 2606892. PMID 18852329.^ Haas VK, Kohn MR, Clarke SD, Allen JR, Madden S, Müller MJ, Gaskin KJ (April 2009). ""Body composition changes in female adolescents with anorexia nervosa"". The American Journal of Clinical Nutrition. 89 (4): 1005–10. doi: 10.3945/ajcn.2008.26958. PMID 19211813.^ Brummett BH, Kuhn CM, Boyle SH, Babyak MA, Siegler IC, Williams RB (January 2012). ""Cortisol responses to emotional stress in men: association with a functional polymorphism in the 5HTR2C gene"" (PDF). Biological Psychology. 89 (1): 94–8. doi: 10.1016/j.biopsycho.2011.09.013. PMC 3245751. PMID 21967853.^ Ceballos NA, Sharma S, Patterson TL, Graham R, Howard K (November 2015). ""Stress, Immune Function and Collegiate Holiday Drinking: A Pilot Study"". Neuropsychobiology. 72 (1): 8–15. doi: 10.1159/000438757. PMID 26304312.^ Häggström, Mikael; Richfield, David (2014). ""Diagram of the pathways of human steroidogenesis"". Wiki Journal of Medicine. 1 (1). doi: 10.15347/wjm/2014.005. ISSN 2002-4436.^ Willett LB, Erb RE (January 1972). ""Short term changes in plasma corticoids in dairy cattle"". Journal of Animal Science. 34 (1): 103–11. doi: 10.2527/jas1972.341103x. PMID 5062063.^ Margioris AN, Tsatsanis C (2011). ""ACTH Action on the Adrenal"". In Chrousos G. Adrenal physiology and diseases. Endotext.org.^ Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM (October 2004). ""11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response"". Endocrine Reviews. 25 (5): 831–66. doi: 10.1210/er.2003-0031. PMID 15466942.^ van Staaveren, N., Teixeira, D. L., Hanlon, A. and Boyle, L. A. (2015). ""The effect of mixing entire male pigs prior to transport to slaughter on behaviour, welfare and carcass lesions"". PLo S One. 10 (4): e0122841. Bibcode: 2015PLo SO..1022841V. doi: 10.1371/journal.pone.0122841. PMC 4382277. PMID 25830336.^ van Staaveren N, Teixeira DL, Hanlon A, Boyle LA (1997). ""The effect of mixing entire male pigs prior to transport to slaughter on behaviour, welfare and carcass lesions"". PLo S One. 10 (4): e0122841. Bibcode: 2015PLo SO..1022841V. doi: 10.1371/journal.pone.0122841. PMC 4382277. PMID 25830336.^ Schalke E, Stichnoth J, Ott S, Jones-Baade R (2007). ""Clinical signs caused by the use of electric training collars on dogs in everyday life situations"". Applied Animal Behaviour Science. 105 (4): 369–380. doi: 10.1016/j.applanim.2006.11.002.^ a b Accorsi PA, Carloni E, Valsecchi P, Viggiani R, Gamberoni M, Tamanini C, Seren E (January 2008). ""Cortisol determination in hair and faeces from domestic cats and dogs"". General and Comparative Endocrinology. 155 (2): 398–402. doi: 10.1016/j.ygcen.2007.07.002. PMID 17727851.^ Möstl E, Messmann S, Bagu E, Robia C, Palme R (December 1999). ""Measurement of glucocorticoid metabolite concentrations in faeces of domestic livestock"". Zentralblatt für Veterinarmedizin. Reihe A. 46 (10): 621–31. PMID 10638300. External links [ edit]Wikimedia Commons has media related to Cortisol. Cortisol MS Spectrum Cortisol (serum/plasma) at Lab Tests Online Cortisol: analyte monograph – The Association for Clinical Biochemistry and Laboratory Medicine [ show]v t e Hormones [ show]v t e Endogenous steroids [ show]v t e Glucocorticoid receptor modulators [ show]v t e Mineralocorticoid receptor modulators Authority control LCCN: sh85063384 GND: 4160902-5Categories: Anxiety Glucocorticoids Otologicals Pregnanes Stress "
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"\"From Wikipedia, the free encyclopedia (Redirected from Stress hormone)navigation search This article is about the natural hormone.",
"For the medication, see Hydrocortisone.",
"Not to be confused with cortisone, a metabolite from cortisol, with a similar name, genesis, and function.",
"This article's lead section may not adequately summarize its contents.",
"To comply with Wikipedia's lead section guidelines, please consider modifying the lead to provide an accessible overview of the article's key points in such a way that it can stand on its own as a concise version of the article.",
"( discuss).",
"(November 2016)Cortisol Names IUPAC name11β,17α,21-Trihydroxypregn-4-ene-3,20-dione Identifiers CAS Number50-23-73D model ( JSmol)Interactive image Ch EBICHEBI:17650Ch EMBLCh EMBL389621Chem Spider5551Drug Bank DB00741ECHA Info Card 100.000.019KEGGD00088Pub Chem CID5754UNIIWI4X0X7BPJIn Ch I [show]SMILES [show]Properties Chemical formula C 21 H 30 O 5Molar mass 362.460 g/mol Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 k Pa).",
"Infobox references Cortisol is a steroid hormone, in the glucocorticoid class of hormones.",
"When used as a medication, it is known as hydrocortisone.",
"It is produced in humans by the zona fasciculata of the adrenal cortex within the adrenal gland.",
"[1] It is released in response to stress and low blood-glucose concentration.",
"It functions to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates.",
"[2] It also decreases bone formation.",
"[3]Contents [ hide ]1 Health effects1.1 Metabolic response1.2 Immune response2 Other effects2.1 Metabolism2.2 Wound healing2.3 Electrolyte balance2.4 Stomach and kidneys2.5 Memory2.6 Sleep, stress, and mood2.7 Effects during pregnancy3 Synthesis and release3.1 Normal levels3.2 Disorders of cortisol production4 Regulation4.1 Factors reducing cortisol levels4.2 Factors increasing cortisol levels5 Biochemistry5.1 Biosynthesis5.2 Metabolism6 Chemistry7 Other animals8 See also9 References10 External links Health effects [ edit]Metabolic response [ edit]In the early fasting state, cortisol stimulates gluconeogenesis (the formation of glucose), and activates antistress and anti-inflammatory pathways.",
"Cortisol also plays an important, but indirect, role in liver and muscle glycogenolysis, the breaking down of glycogen to glucose-1-phosphate and glucose.",
"This is done through its passive influence on glucagon.",
"[ clarification needed] Additionally, cortisol facilitates the activation of glycogen phosphorylase, which is necessary for epinephrine to have an effect on glycogenolysis.",
"[4] [5]In the late fasting state, the function of cortisol changes slightly and increases glycogenesis.",
"This response allows the liver to take up glucose not being used by the peripheral tissue and turn it into liver glycogen stores to be used if the body moves into the starvation state.",
"[ citation needed]Elevated levels of cortisol, if prolonged, can lead to proteolysis (breakdown of proteins) and muscle wasting.",
"[6] Several studies have shown that cortisol can have a lipolytic effect (promote the breakdown of fat).",
"Under some conditions, however, cortisol may somewhat suppress lipolysis.",
"[7]Immune response [ edit]Cortisol prevents the release of substances in the body that cause inflammation.",
"It is used to treat conditions resulting from overactivity of the B-cell-mediated antibody response.",
"Examples include inflammatory and rheumatoid diseases, as well as allergies.",
"Low-potency hydrocortisone, available as a nonprescription medicine in some countries, is used to treat skin problems such as rashes and eczema.",
"It inhibits production of interleukin (IL)-12, interferon (IFN)-gamma, IFN-alpha, and tumor-necrosis-factor (TNF)-alpha by antigen-presenting cells (APCs) and T helper (Th)1 cells, but upregulates IL-4, IL-10, and IL-13 by Th2 cells.",
"This results in a shift toward a Th2 immune response rather than general immunosuppression.",
"The activation of the stress system (and resulting increase in cortisol and Th2 shift) seen during an infection is believed to be a protective mechanism which prevents an over-activation of the inflammatory response.",
"[8]Cortisol can weaken the activity of the immune system.",
"It prevents proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor ( IL-2 ).",
"[9] Cortisol also has a negative-feedback effect on interleukin-1.",
"[10]Though IL-1 is useful in combating some diseases, endotoxic bacteria have gained an advantage by forcing the hypothalamus to increase cortisol levels (forcing the secretion of corticotropin-releasing hormone, thus antagonizing IL-1).",
"The suppressor cells are not affected by glucosteroid response-modifying factor, [11] so the effective setpoint for the immune cells may be even higher than the setpoint for physiological processes (reflecting leukocyte redistribution to lymph nodes, bone marrow, and skin ).",
"Rapid administration of corticosterone (the endogenous type I and type II receptor agonist) or RU28362 (a specific type II receptor agonist) to adrenalectomized animals induced changes in leukocyte distribution.",
"Natural killer cells are affected by cortisol.",
"[12]Cortisol stimulates many copper enzymes (often to 50% of their total potential), probably to increase copper availability for immune purposes.",
"[13]: 337 This includes lysyl oxidase, an enzyme that cross-links collagen, and elastin.",
"[13]: 334 Especially valuable for immune response is cortisol's stimulation of the superoxide dismutase, [14] since this copper enzyme is almost certainly used by the body to permit superoxides to poison bacteria.",
"Other effects [ edit]Metabolism [ edit]Glucose [ edit]Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis [15] and inhibits the peripheral use of glucose ( insulin resistance) [15] by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane.",
"[16] Cortisol increases blood glucose levels by increasing glycogen synthesis (glycogenesis) in the liver.",
"[17] The permissive effect of cortisol on insulin action in liver glycogenesis is observed in hepatocyte culture in the laboratory, although the mechanism for this is unknown.",
"Bone and collagen [ edit]Cortisol reduces bone formation, [3] favoring long-term development of osteoporosis (progressive bone disease).",
"It transports potassium out of cells in exchange for an equal number of sodium ions (see above).",
"[18] This can trigger the hyperkalemia of metabolic shock from surgery.",
"Cortisol also reduces calcium absorption in the intestine.",
"[19]Collagen is an important component of connective tissue.",
"It is vital for structural support and is found in muscles, tendons, and joints, as well as throughout the entire body.",
"Cortisol down-regulates the synthesis of collagen.",
"[20]Amino acid [ edit]Cortisol raises the free amino acids in the serum by inhibiting collagen formation, decreasing amino acid uptake by muscle, and inhibiting protein synthesis.",
"[21] Cortisol (as opticortinol) may inversely inhibit Ig A precursor cells in the intestines of calves.",
"[22] Cortisol also inhibits Ig A in serum, as it does Ig M; however, it is not shown to inhibit Ig E. [23]Wound healing [ edit]Cortisol and the stress response have known deleterious effects on the immune system.",
"High levels of perceived stress and increases in cortisol have been found to lengthen wound-healing time in healthy, male adults.",
"Those who had the lowest levels of cortisol the day following a 4 mm punch biopsy had the fastest healing time.",
"[24] In dental students, wounds from punch biopsies took an average of 40% longer to heal when performed three days before an examination as opposed to biopsies performed on the same students during summer vacation.",
"[25] This is in line with previous animal studies that show similar detrimental effects on wound healing, notably the primary reports showing that turtles recoil from cortisol.",
"[26]Electrolyte balance [ edit]Cortisol acts as a diuretic, increasing water diuresis, glomerular filtration rate, and renal plasma flow from the kidneys, as well as increasing sodium retention and potassium excretion.",
"It also increases sodium and water absorption and potassium excretion in the intestines.",
"[27]Sodium [ edit]Cortisol promotes sodium absorption through the small intestine of mammals.",
"[28] Sodium depletion, however, does not affect cortisol levels [29] so cortisol cannot be used to regulate serum sodium.",
"Cortisol's original purpose may have been sodium transport.",
"This hypothesis is supported by the fact that freshwater fish use cortisol to stimulate sodium inward, while saltwater fish have a cortisol-based system for expelling excess sodium.",
"[30]Potassium [ edit]A sodium load augments the intense potassium excretion by cortisol.",
"Corticosterone is comparable to cortisol in this case.",
"[31] For potassium to move out of the cell, cortisol moves an equal number of sodium ions into the cell.",
"[18] This should make p H regulation much easier (unlike the normal potassium-deficiency situation, in which two sodium ions move in for each three potassium ions that move out—closer to the deoxycorticosterone effect).",
"Stomach and kidneys [ edit]Cortisol stimulates gastric-acid secretion.",
"[32] Cortisol's only direct effect on the hydrogen-ion excretion of the kidneys is to stimulate the excretion of ammonium ions by deactivating the renal glutaminase enzyme.",
"[33]Memory [ edit]Cortisol works with epinephrine (adrenaline) to create memories of short-term emotional events; this is the proposed mechanism for storage of flash-bulb memories, and may originate as a means to remember what to avoid in the future.",
"[34] However, long-term exposure to cortisol damages cells in the hippocampus; [35] this damage results in impaired learning.",
"Furthermore, cortisol inhibits memory retrieval of already stored information.",
"[36] [37]Sleep, stress, and mood [ edit]Diurnal cycles of cortisol levels are found in humans.",
"[4] In humans, the amount of cortisol present in the blood undergoes diurnal variation; the level peaks in the early morning (around 8 am) and reaches its lowest level at about midnight-4 am, or three to five hours after the onset of sleep.",
"Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus.",
"This pattern is not present at birth; estimates of when it begins vary from two weeks to nine months of age.",
"[38]Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, mood disorders such as major depressive disorder, anxiety disorders, psychological stress, and physiological stressors such as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion, or temperature extremes.",
"Cortisol levels may also differ for individuals with autism or Asperger's syndrome.",
"[39] Also, significant individual variation is seen, although a given person tends to have consistent rhythms.",
"Effects during pregnancy [ edit]During human pregnancy, increased fetal production of cortisol between weeks 30 and 32 initiates production of fetal lung surfactant to promote maturation of the lungs.",
"In fetal lambs, glucocorticoids (principally cortisol) increase after about day 130, with lung surfactant increasing greatly, in response, by about day 135, [40] and although lamb fetal cortisol is mostly of maternal origin during the first 122 days, 88% or more is of fetal origin by day 136 of gestation.",
"[41] Although the timing of fetal cortisol concentration elevation in sheep may vary somewhat, it averages about 11.8 days before the onset of labor.",
"[42] In several livestock species (e.g.",
"cattle, sheep, goats, and pigs), the surge of fetal cortisol late in gestation triggers the onset of parturition by removing the progesterone block of cervical dilation and myometrial contraction.",
"The mechanisms yielding this effect on progesterone differ among species.",
"In the sheep, where progesterone sufficient for maintaining pregnancy is produced by the placenta after about day 70 of gestation, [43] [44] the prepartum fetal cortisol surge induces placental enzymatic conversion of progesterone to estrogen.",
"(The elevated level of estrogen stimulates prostaglandin secretion and oxytocin receptor development.",
")Exposure of fetuses to cortisol during gestation can have a variety of developmental outcomes, including alterations in prenatal and postnatal growth patterns.",
"In marmosets, a species of New World primates, pregnant females have varying levels of cortisol during gestation, both within and between females.",
"Infants born to mothers with high gestational cortisol during the first trimester of pregnancy had lower rates of growth in body mass indices than infants born to mothers with low gestational cortisol (about 20% lower).",
"However, postnatal growth rates in these high-cortisol infants was more rapid than low-cortisol infants later in postnatal periods, and complete catch-up in growth had occurred by 540 days of age.",
"These results suggest that gestational exposure to cortisol in fetuses has important potential fetal programming effects on both pre- and postnatal growth in primates.",
"[45]Synthesis and release [ edit]Cortisol is produced in the human body by the adrenal gland in the zona fasciculata, [1] the second of three layers comprising the adrenal cortex.",
"The cortex forms the outer \"\"bark\"\" of each adrenal gland, situated atop the kidneys.",
"The release of cortisol is controlled by the hypothalamus, a part of the brain.",
"The secretion of corticotropin-releasing hormone by the hypothalamus [46] triggers cells in the neighboring anterior pituitary to secrete another hormone, the adrenocorticotropic hormone (ACTH), into the vascular system, through which blood carries it to the adrenal cortex.",
"ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids, and dehydroepiandrosterone.",
"Normal levels [ edit]Normal values indicated in the following tables pertain to humans (normal levels vary among species).",
"Measured cortisol levels, and therefore reference ranges, depend on the analytical method used and factors such as age and sex.",
"Test results should, therefore, always be interpreted using the reference range from the laboratory that produced the result.",
"Reference ranges for blood plasma content of free cortisol Time Lower limit Upper limit Unit09:00 am 140 [47] 700 [47] nmol/L5 [48] 25 [48] μg/d LMidnight 80 [47] 350 [47] nmol/l2.9 [48] 13 [48] μg/dl Using the molecular weight of 362.460 g/mole, the conversion factor from µg/dl to nmol/l is approximately 27.6; thus, 10 µg/dl is about 276 nmol/l.",
"Reference ranges for urinalysis of free cortisol Lower limit Upper limit Unit28 [49] or 30 [50] 280 [49] or 490 [50] nmol /24h10 [51] or 11 [52] 100 [51] or 176 [52] µg /24 h Disorders of cortisol production [ edit]Cushing's syndrome or hypercortisolism: Excessive levels of cortisol in the blood Hypocortisolism: Insufficient levels of cortisol in the blood Disorders of cortisol production, and some consequent conditions, are: Primary hypercortisolism (Cushing's syndrome)Primary hypocortisolism ( Addison's disease, Nelson's syndrome )Secondary hypercortisolism (pituitary tumor resulting in Cushing's disease, [53] [54] pseudo-Cushing's syndrome)Secondary hypocortisolism (pituitary tumor, Sheehan's syndrome)Regulation [ edit]The primary control of cortisol is the pituitary gland peptide, ACTH, which probably controls cortisol by controlling the movement of calcium into the cortisol-secreting target cells.",
"[55] ACTH is in turn controlled by the hypothalamic peptide corticotropin-releasing hormone (CRH), which is under nervous control.",
"CRH acts synergistically with arginine vasopressin, angiotensin II, and epinephrine.",
"[56] (In swine, which do not produce arginine vasopressin, lysine vasopressin acts synergistically with CRH.",
"[57])When activated macrophages start to secrete IL-1, which synergistically with CRH increases ACTH, [10] T-cells also secrete glucosteroid response modifying factor (GRMF), as well as IL-1; both increase the amount of cortisol required to inhibit almost all the immune cells.",
"[11] Immune cells then assume their own regulation, but at a higher cortisol setpoint.",
"The increase in cortisol in diarrheic calves is minimal over healthy calves, however, and falls over time.",
"[58] The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH.",
"Cortisol even has a negative feedback effect on interleukin-1 [10] —especially useful to treat diseases that force the hypothalamus to secrete too much CRH, such as those caused by endotoxic bacteria.",
"The suppressor immune cells are not affected by GRMF, [11] so the immune cells' effective setpoint may be even higher than the setpoint for physiological processes.",
"GRMF affects primarily the liver (rather than the kidneys) for some physiological processes.",
"[59]High-potassium media (which stimulates aldosterone secretion in vitro) also stimulate cortisol secretion from the fasciculata zone of canine adrenals [60] [61] — unlike corticosterone, upon which potassium has no effect.",
"[62]Potassium loading also increases ACTH and cortisol in humans.",
"[63] This is probably the reason why potassium deficiency causes cortisol to decline (as mentioned) and causes a decrease in conversion of 11-deoxycortisol to cortisol.",
"[64] This may also have a role in rheumatoid-arthritis pain; cell potassium is always low in RA.",
"[65]Ascorbic acid presence, particularly in high doses has also been shown to mediate response to psychological stress and speed the decrease of the levels of circulating cortisol in the body post stress.",
"This can be evidenced through a decrease in systolic and diastolic blood pressures and decreased salivary cortisol level after treatment with ascorbic acid.",
"[66]Factors reducing cortisol levels [ edit]Magnesium supplementation decreases serum cortisol levels after aerobic exercise, [67] [68] but not after resistance training.",
"[69]Omega-3 fatty acids have a dose-dependent effect [70] in slightly reducing cortisol release influenced by mental stress, [71] suppressing the synthesis of interleukin -1 and -6 and enhancing the synthesis of interleukin-2; the former promotes higher CRH release.",
"Omega-6 fatty acids, though, have an inverse effect on interleukin synthesis.",
"[72]Music therapy can reduce cortisol levels in certain situations.",
"[73]Massage therapy can reduce cortisol.",
"[74]Laughing, and the experience of humor, can lower cortisol levels.",
"[75]Soy-derived phosphatidylserine interacts with cortisol; the correct dose, however, is unclear.",
"[76] [77] [78] [79]Regular dancing has been shown to lead to significant decreases in salivary cortisol concentrations.",
"[80]Withania somnifera (ashwagandha) root extract [81]High-dosage treatment with ascorbic acid (vitamin C) has been shown to decrease circulating cortisol levels during and shortly after the treatment period.",
"[66]Factors increasing cortisol levels [ edit]Viral infections increase cortisol levels through activation of the HPA axis by cytokines.",
"[82]Caffeine may increase cortisol levels.",
"[83]Sleep deprivation [84]Intense (high VO 2max) or prolonged aerobic exercise transiently increases cortisol levels to increase gluconeogenesis and maintain blood glucose; [85] however, cortisol declines to normal levels after eating (i.e., restoring a neutral energy balance) [86]The Val/Val variation of the BDNF gene in men and the Val/Met variation in women are associated with increased salivary cortisol in a stressful situation.",
"[87]Severe trauma or stressful events can elevate cortisol levels in the blood for prolonged periods.",
"[88]Subcutaneous adipose tissue regenerates cortisol from cortisone by the enzyme 11-beta HSD1.",
"[89]Anorexia nervosa may be associated with increased cortisol levels.",
"[90]The serotonin receptor gene 5HTR2C is associated with increased cortisol production in men.",
"[91]Smelling androstadienone has been found in one study to raise cortisol levels in women, as well as, in other studies, to affect mood (see androstadienone article for details and citations).",
"Excessive or problematic drinking has been linked to increased cortisol levels, especially in college students.",
"[92]Biochemistry [ edit]Biosynthesis [ edit]Steroidogenesis, showing cortisol at right.",
"[93]Cortisol is synthesized from cholesterol.",
"Synthesis takes place in the zona fasciculata of the adrenal cortex.",
"(The name cortisol is derived from cortex.)",
"While the adrenal cortex also produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticularis), cortisol is its main secretion in humans and several other species.",
"(However, in cattle, corticosterone levels may approach [94] or exceed [4] cortisol levels.).",
"The medulla of the adrenal gland lies under the cortex, mainly secreting the catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation.",
"The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with ACTH; ACTH production is, in turn, stimulated by CRH, which is released by the hypothalamus.",
"ACTH increases the concentration of cholesterol in the inner mitochondrial membrane, via regulation of the steroidogenic acute regulatory protein.",
"It also stimulates the main rate-limiting step in cortisol synthesis, in which cholesterol is converted to pregnenolone and catalyzed by cytochrome P450SCC ( side-chain cleavage enzyme ).",
"[95]Metabolism [ edit]Cortisol is metabolized by the 11-beta hydroxysteroid dehydrogenase system (11-beta HSD), which consists of two enzymes: 11-beta HSD1 and 11-beta HSD2.11-beta HSD1 uses the cofactor NADPH to convert biologically inert cortisone to biologically active cortisol11-beta HSD2 uses the cofactor NAD+ to convert cortisol to cortisone Overall, the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue; 11-beta HSD2 serves to decrease local concentrations of biologically active cortisol.",
"Cortisol is also metabolized into 5-alpha tetrahydrocortisol (5-alpha THF) and 5-beta tetrahydrocortisol (5-beta THF), reactions for which 5-alpha reductase and 5-beta reductase are the rate-limiting factors, respectively.",
"5-Beta reductase is also the rate-limiting factor in the conversion of cortisone to tetrahydrocortisone.",
"An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis of obesity, hypertension, and insulin resistance known as metabolic syndrome.",
"[96]An alteration in 11-beta HSD2 has been implicated in essential hypertension and is known to lead to the syndrome of apparent mineralocorticoid excess (SAME).",
"Chemistry [ edit]Cortisol is a naturally occurring pregnane corticosteroid and is also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione.",
"Other animals [ edit]In non-human animals, cortisol is often used as an indicator of stress and can be measured in blood, [97] saliva, [98] urine, [99] hair, [100] and faeces.",
"[100] [101]See also [ edit]Cortisone, a hormone Membrane glucocorticoid receptor List of corticosteroids References [ edit]^ a b Scott E (2011-09-22).",
"\"\"Cortisol and Stress: How to Stay Healthy\"\".",
"About.com.",
"Retrieved 2011-11-29.",
"[ better source needed]^ Hoehn K, Marieb EN (2010).",
"Human Anatomy & Physiology.",
"San Francisco: Benjamin Cummings.",
"ISBN 0-321-60261-7.^ a b Chyun YS, Kream BE, Raisz LG (February 1984).",
"\"\"Cortisol decreases bone formation by inhibiting periosteal cell proliferation\"\".",
"Endocrinology.",
"114 (2): 477–80.",
"doi: 10.1210/endo-114-2-477.",
"PMID 6690287.^ a b c Martin PA, Crump MH (2003).",
"\"\"The adrenal gland\"\".",
"In Dooley MP, Pineda MH.",
"Mc Donald's veterinary endocrinology and reproduction (5th ed.).",
"Ames, Iowa: Iowa State Press.",
"ISBN 0-8138-1106-6.^ Coderre L, Srivastava AK, Chiasson JL (June 1991).",
"\"\"Role of glucocorticoid in the regulation of glycogen metabolism in skeletal muscle\"\".",
"The American Journal of Physiology.",
"260 (6 Pt 1): E927–32.",
"PMID 1905485.^ Simmons PS, Miles JM, Gerich JE, Haymond MW (February 1984).",
"\"\"Increased proteolysis.",
"An effect of increases in plasma cortisol within the physiologic range\"\".",
"The Journal of Clinical Investigation.",
"73 (2): 412–20.",
"doi: 10.1172/JCI111227.",
"PMC 425032.",
"PMID 6365973.^ Djurhuus CB, Gravholt CH, Nielsen S, Mengel A, Christiansen JS, Schmitz OE, Møller N (July 2002).",
"\"\"Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans\"\".",
"American Journal of Physiology.",
"Endocrinology and Metabolism.",
"283 (1): E172–7.",
"doi: 10.1152/ajpendo.00544.2001.",
"PMID 12067858.^ Elenkov IJ (June 2004).",
"\"\"Glucocorticoids and the Th1/Th2 balance\"\".",
"Annals of the New York Academy of Sciences.",
"1024 (1): 138–46.",
"Bibcode: 2004NYASA1024..138E.",
"doi: 10.1196/annals.1321.010.",
"PMID 15265778.^ Palacios R, Sugawara I (January 1982).",
"\"\"Hydrocortisone abrogates proliferation of T cells in autologous mixed lymphocyte reaction by rendering the interleukin-2 Producer T cells unresponsive to interleukin-1 and unable to synthesize the T-cell growth factor\"\".",
"Scandinavian Journal of Immunology.",
"15 (1): 25–31.",
"doi: 10.1111/j.1365-3083.1982.tb00618.x.",
"PMID 6461917.^ a b c Besedovsky HO, Del Rey A, Sorkin E (1986).",
"\"\"Integration of Activated Immune Cell Products in Immune Endocrine Feedback Circuits\"\".",
"In Oppenheim JJ, Jacobs DM.",
"Leukocytes and Host Defense.",
"Progress in Leukocyte Biology.",
"5.",
"New York: Alan R. Liss.",
"p. 200.^ a b c Fairchild SS, Shannon K, Kwan E, Mishell RI (February 1984).",
"\"\"T cell-derived glucosteroid response-modifying factor (GRMFT): a unique lymphokine made by normal T lymphocytes and a T cell hybridoma\"\".",
"Journal of Immunology.",
"132 (2): 821–7.",
"PMID 6228602.^ Mavoungou E, Bouyou-Akotet MK, Kremsner PG (February 2005).",
"\"\"Effects of prolactin and cortisol on natural killer (NK) cell surface expression and function of human natural cytotoxicity receptors (NKp46, NKp44 and NKp30)\"\".",
"Clinical and Experimental Immunology.",
"139 (2): 287–96.",
"doi: 10.1111/j.1365-2249.2004.02686.x.",
"PMC 1809301.",
"PMID 15654827.^ a b Weber CE (December 1984).",
"\"\"Copper response to rheumatoid arthritis\"\".",
"Medical Hypotheses.",
"15 (4): 333–48.",
"doi: 10.1016/0306-9877 (84)90150-6.",
"PMID 6152006.^ Flohe L, Beckman R, Giertz H, Loschen G (1985).",
"\"\"Oxygen Centered Free Radicals as Mediators of Inflammation\"\".",
"In Sies H. Oxidative stress.",
"London: Orlando.",
"p. 405.",
"ISBN 0-12-642760-7.^ a b Brown DF, Brown DD (2003).",
"USMLE Step 1 Secrets: Questions You Will Be Asked on USMLE Step 1.",
"Philadelphia: Hanley & Belfus.",
"p. 63.",
"ISBN 1-56053-570-9.",
"[ better source needed]^ King MB (2005).",
"Lange Q & A.",
"New York: Mc Graw-Hill, Medical Pub.",
"Division.",
"ISBN 0-07-144578-1.^ Baynes J, Dominiczak M (2009).",
"Medical biochemistry.",
"Mosby Elsevier.",
"ISBN 0-323-05371-8.^ a b Knight RP, Kornfeld DS, Glaser GH, Bondy PK (February 1955).",
"\"\"Effects of intravenous hydrocortisone on electrolytes of serum and urine in man\"\".",
"The Journal of Clinical Endocrinology and Metabolism.",
"15 (2): 176–81.",
"doi: 10.1210/jcem-15-2-176.",
"PMID 13233328.^ Deutsch E (April 1978). \"\"",
"[Pathogenesis of thrombocytopenia.",
"2.",
"Distribution disorders, pseudo-thrombocytopenias]\"\".",
"Fortschritte Der Medizin (in German).",
"96 (14): 761–2.",
"PMID 346457.^ Kucharz EJ (1988).",
"\"\"Hormonal control of collagen metabolism.",
"Part II\"\".",
"Endocrinologie.",
"26 (4): 229–37.",
"PMID 3062759.^ Manchester, KL (1964).",
"\"\"Sites of Hormonal Regulation of Protein Metabolism\"\".",
"In Allison, NH & Munro JB.",
"Mammalian Protein Metabolism.",
"New York: Academic Press.",
"p. 229?",
"273?.^ Husband AJ, Brandon MR, Lascelles AK (October 1973).",
"\"\"The effect of corticosteroid on absorption and endogenous production of immunoglobulins in calves\"\".",
"The Australian Journal of Experimental Biology and Medical Science.",
"51 (5): 707–10.",
"doi: 10.1038/icb.1973.67.",
"PMID 4207041.^ Posey WC, Nelson HS, Branch B, Pearlman DS (December 1978).",
"\"\"The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels\"\".",
"The Journal of Allergy and Clinical Immunology.",
"62 (6): 340–8.",
"doi: 10.1016/0091-6749 (78)90134-3.",
"PMID 712020.^ Ebrecht M, Hextall J, Kirtley LG, Taylor A, Dyson M, Weinman J (July 2004).",
"\"\"Perceived stress and cortisol levels predict speed of wound healing in healthy male adults\"\".",
"Psychoneuroendocrinology.",
"29 (6): 798–809.",
"doi: 10.1016/s0306-4530 (03)00144-6.",
"PMID 15110929.^ Marucha PT, Kiecolt-Glaser JK, Favagehi M (1998).",
"\"\"Mucosal wound healing is impaired by examination stress\"\".",
"Psychosomatic Medicine.",
"60 (3): 362–5.",
"doi: 10.1097/00006842-199805000-00025.",
"PMID 9625226.^ Zhou X, Xie M, Niu C, Sun R (June 2003).",
"\"\"The effects of dietary vitamin C on growth, liver vitamin C and serum cortisol in stressed and unstressed juvenile soft-shelled turtles (Pelodiscus sinensis)\"\".",
"Comparative Biochemistry and Physiology.",
"Part A, Molecular & Integrative Physiology.",
"135 (2): 263–70.",
"doi: 10.1016/s1095-6433 (03)00066-7.",
"PMID 12781826.^ Mc Kay LI, Cidlowski JA (2003).",
"\"\"Physiologic and Pharmacologic Effects of Corticosteroids\"\".",
"In Kure DW, Pollock RE, Weichselbaum RR, Bast RC, Ganglier TS, Holland JF, Frei E. Holland-Frei Cancer Medicine (6 ed.).",
"Hamilton, Ontario: Decker.",
"ISBN 978-1-55009-213-4.^ Sandle GI, Keir MJ, Record CO (1981).",
"\"\"The effect of hydrocortisone on the transport of water, sodium, and glucose in the jejunum.",
"Perfusion studies in normal subjects and patients with coeliac disease\"\".",
"Scandinavian Journal of Gastroenterology.",
"16 (5): 667–71.",
"doi: 10.3109/00365528109182028.",
"PMID 7323700.^ Mason PA, Fraser R, Morton JJ, Semple PF, Wilson A (August 1977).",
"\"\"The effect of sodium deprivation and of angiotensin II infusion on the peripheral plasma concentrations of 18-hydroxycorticosterone, aldosterone and other corticosteroids in man\"\".",
"Journal of Steroid Biochemistry.",
"8 (8): 799–804.",
"doi: 10.1016/0022-4731 (77)90086-3.",
"PMID 592808.^ Gorbman A, Dickhoff WW, Vigna SR, Clark NB, Muller AF (1983).",
"Comparative endocrinology.",
"New York: Wiley.",
"ISBN 0-471-06266-9.^ Muller AF, Oconnor CM (1958).",
"An International Symposium on Aldosterone.",
"Little Brown & Co. p. 58.^ Soffer LJ, Dorfman RI, Gabrilove JL (1961).",
"The Human Adrenal Gland.",
"Philadelphia: Lea & Febiger.^ Kokoshchuk GI, Pakhmurnyĭ BA (May 1979). \"\"",
"[Role of glucocorticoids in regulating the acid-excreting function of the kidneys]\"\".",
"Fiziologicheskii Zhurnal SSSR Imeni I. M. Sechenova.",
"65 (5): 751–4.",
"PMID 110627.^ Kennedy, Ron.",
"\"\"Cortisol (Hydrocortisone)\"\".",
"The Doctors' Medical Library.",
"Retrieved 14 June 2013.^ Mc Auley MT, Kenny RA, Kirkwood TB, Wilkinson DJ, Jones JJ, Miller VM (March 2009).",
"\"\"A mathematical model of aging-related and cortisol induced hippocampal dysfunction\"\".",
"BMC Neuroscience.",
"10: 26. doi: 10.1186/1471-2202-10-26.",
"PMC 2680862.",
"PMID 19320982.^ de Quervain DJ, Roozendaal B, Mc Gaugh JL (August 1998).",
"\"\"Stress and glucocorticoids impair retrieval of long-term spatial memory\"\".",
"Nature.",
"394 (6695): 787–90.",
"Bibcode: 1998Natur.394..787D.",
"doi: 10.1038/29542.",
"PMID 9723618.^ de Quervain DJ, Roozendaal B, Nitsch RM, Mc Gaugh JL, Hock C (April 2000).",
"\"\"Acute cortisone administration impairs retrieval of long-term declarative memory in humans\"\".",
"Nature Neuroscience.",
"3 (4): 313–4.",
"doi: 10.1038/73873.",
"PMID 10725918.^ de Weerth C, Zijl RH, Buitelaar JK (August 2003).",
"\"\"Development of cortisol circadian rhythm in infancy\"\".",
"Early Human Development.",
"73 (1–2): 39–52.",
"doi: 10.1016/S0378-3782 (03)00074-4.",
"PMID 12932892.^ \"\"Asperger's stress hormone 'link ' \"\".",
"BBC News Online.",
"2009-04-02.",
"Retrieved 2010-04-30.^ Mescher EJ, Platzker AC, Ballard PL, Kitterman JA, Clements JA, Tooley WH (December 1975).",
"\"\"Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb\"\".",
"Journal of Applied Physiology.",
"39 (6): 1017–21.",
"PMID 2573.^ Hennessy DP, Coghlan JP, Hardy KJ, Scoggins BA, Wintour EM (October 1982).",
"\"\"The origin of cortisol in the blood of fetal sheep\"\".",
"The Journal of Endocrinology.",
"95 (1): 71–9.",
"doi: 10.1677/joe.0.0950071.",
"PMID 7130892.^ Magyar DM, Fridshal D, Elsner CW, Glatz T, Eliot J, Klein AH, Lowe KC, Buster JE, Nathanielsz PW (July 1980).",
"\"\"Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition\"\".",
"Endocrinology.",
"107 (1): 155–9.",
"doi: 10.1210/endo-107-1-155.",
"PMID 7379742.^ Ricketts AP, Flint AP (August 1980).",
"\"\"Onset of synthesis of progesterone by ovine placenta\"\".",
"The Journal of Endocrinology.",
"86 (2): 337–47.",
"doi: 10.1677/joe.0.0860337.",
"PMID 6933207.^ Al-Gubory KH, Solari A, Mirman B (1999).",
"\"\"Effects of luteectomy on the maintenance of pregnancy, circulating progesterone concentrations and lambing performance in sheep\"\".",
"Reproduction, Fertility, and Development.",
"11 (6): 317–22.",
"doi: 10.1071/RD99079.",
"PMID 10972299.^ Mustoe AC, Birnie AK, Korgan AC, Santo JB, French JA (February 2012).",
"\"\"Natural variation in gestational cortisol is associated with patterns of growth in marmoset monkeys (Callithrix geoffroyi)\"\".",
"General and Comparative Endocrinology.",
"175 (3): 519–26.",
"doi: 10.1016/j.ygcen.2011.12.020.",
"PMC 3268124.",
"PMID 22212825.^ \"\"You & Your Hormones : Cortisol\"\".",
"the Society for Endocrinology (Last updated) :.",
"October 24, 2013.",
"Archived from the original on November 24, 2014.",
"Retrieved November 24, 2014.^ a b c d Biochemistry Reference Ranges at Good Hope Hospital Retrieved 8 November 2009 [ better source needed]^ a b c d Derived from molar values using molar mass of 362 g/mol^ a b Converted from µg/24h, using molar mass of 362.460 g/mol^ a b Görges R, Knappe G, Gerl H, Ventz M, Stahl F (April 1999).",
"\"\"Diagnosis of Cushing's syndrome: re-evaluation of midnight plasma cortisol vs urinary free cortisol and low-dose dexamethasone suppression test in a large patient group\"\".",
"Journal of Endocrinological Investigation.",
"22 (4): 241–9.",
"doi: 10.1007/bf03343551.",
"PMID 10342356.^ a b Medline Plus Encyclopedia Cortisol – urine^ a b Converted from nmol/24h, using molar mass of 362.460 g/mol^ \"\"Cushing's Syndrome\"\".",
"National Endocrine and Metabolic Diseases Information Service (NEMDIS).",
"July 2008.",
"Retrieved 16 March 2015.",
"These benign, or noncancerous, tumors of the pituitary gland secrete extra ACTH.",
"Most people with the disorder have a single adenoma.",
"This form of the syndrome, known as Cushing's disease^ Forbis P (2005).",
"Stedman's medical eponyms (2nd ed.).",
"Baltimore, Md.",
": Lippincott Williams & Wilkins.",
"p. 167.",
"ISBN 978-0-7817-5443-9.^ Davies E, Kenyon CJ, Fraser R (June 1985).",
"\"\"The role of calcium ions in the mechanism of ACTH stimulation of cortisol synthesis\"\".",
"Steroids.",
"45 (6): 551–60.",
"doi: 10.1016/0039-128X (85)90019-4.",
"PMID 3012830.^ Plotsky PM, Otto S, Sapolsky RM (September 1986).",
"\"\"Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback\"\".",
"Endocrinology.",
"119 (3): 1126–30.",
"doi: 10.1210/endo-119-3-1126.",
"PMID 3015567.^ Minton JE, Parsons KM (March 1993).",
"\"\"Adrenocorticotropic hormone and cortisol response to corticotropin-releasing factor and lysine vasopressin in pigs\"\".",
"Journal of Animal Science.",
"71 (3): 724–9.",
"PMID 8385088.^ Dvorak M (1971).",
"\"\"Plasma 17-Hydroxycorticosteroid Levels in Healthy and Diarrheic Calves\"\".",
"British Veterinarian Journal.",
"127: 372.^ Stith RD, Mc Callum RE (1986).",
"\"\"General effect of endotoxin on glucocorticoid receptors in mammalian tissues\"\".",
"Circulatory Shock.",
"18 (4): 301–9.",
"PMID 3084123.^ Mikosha AS, Pushkarov IS, Chelnakova IS, Remennikov GY (1991).",
"\"\"Potassium Aided Regulation of Hormone Biosynthesis in Adrenals of Guinea Pigs Under Action of Dihydropyridines: Possible Mechanisms of Changes in Steroidogenesis Induced by 1,4, Dihydropyridines in Dispersed Adrenocorticytes\"\".",
"Fiziol.",
"[Kiev].",
"37: 60.^ \"\"Ameer Saadallah Al – Zacko\"\" (PDF).",
"Retrieved 11 July 2013.^ Mendelsohn FA, Mackie C (July 1975).",
"\"\"Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells\"\".",
"Clinical Science and Molecular Medicine.",
"49 (1): 13–26.",
"doi: 10.1042/cs0490013.",
"PMID 168026.^ Ueda Y, Honda M, Tsuchiya M, Watanabe H, Izumi Y, Shiratsuchi T, Inoue T, Hatano M (April 1982).",
"\"\"Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension\"\".",
"Japanese Circulation Journal.",
"46 (4): 317–22.",
"doi: 10.1253/jcj.46.317.",
"PMID 6283190.^ Bauman K, Muller J (1972).",
"\"\"Effect of potassium on the final status of aldosterone biosynthesis in the rat.",
"I 18-hydroxylation and 18hydroxy dehydrogenation.",
"II beta-hydroxylation\"\".",
"Acta Endocrin.",
"Copenh.",
"69: I 701–717, II 718–730.^ La Celle PL, Morgan ES, Atwater EC (1964).",
"\"\"An investigation of total body potassium in patients with rheumatoid arthritis\"\".",
"Proceedings of the Annual Meeting of the American Rheumatism Association, Arthritis and Rheumatism.",
"7 (3): 321.^ a b Brody S, Preut R, Schommer K, Schürmeyer TH (January 2002).",
"\"\"A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress\"\".",
"Psychopharmacology.",
"159 (3): 319–24.",
"doi: 10.1007/s00213-001-0929-6.",
"PMID 11862365.^ Golf SW, Happel O, Graef V, Seim KE (November 1984).",
"\"\"Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation\"\".",
"Journal of Clinical Chemistry and Clinical Biochemistry.",
"Zeitschrift für Klinische Chemie Und Klinische Biochemie.",
"22 (11): 717–21.",
"doi: 10.1515/cclm.1984.22.11.717.",
"PMID 6527092.^ Golf SW, Bender S, Grüttner J (September 1998).",
"\"\"On the significance of magnesium in extreme physical stress\"\".",
"Cardiovascular Drugs and Therapy.",
"12 Suppl 2 (2suppl): 197–202.",
"doi: 10.1023/A:1007708918683.",
"PMID 9794094.^ Wilborn CD, Kerksick CM, Campbell BI, Taylor LW, Marcello BM, Rasmussen CJ, Greenwood MC, Almada A, Kreider RB (December 2004).",
"\"\"Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism\"\".",
"Journal of the International Society of Sports Nutrition.",
"1 (2): 12–20.",
"doi: 10.1186/1550-2783-1-2-12.",
"PMC 2129161.",
"PMID 18500945.^ Bhathena SJ, Berlin E, Judd JT, Kim YC, Law JS, Bhagavan HN, Ballard-Barbash R, Nair PP (October 1991).",
"\"\"Effects of omega 3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men\"\".",
"The American Journal of Clinical Nutrition.",
"54 (4): 684–8.",
"PMID 1832814.^ Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L (June 2003).",
"\"\"Fish oil prevents the adrenal activation elicited by mental stress in healthy men\"\".",
"Diabetes & Metabolism.",
"29 (3): 289–95.",
"doi: 10.1016/S1262-3636 (07)70039-3.",
"PMID 12909818.^ Yehuda S (2003).",
"\"\"Omega-6/omega-3 ratio brain related functions\"\".",
"In Simopoulos AP, Cleland LG.",
"Omega-6, omega-3 essential fatty acid ratio: the scientific evidence.",
"Basel: Karger.",
"p. 50.",
"ISBN 3-8055-7640-4.^ Uedo N, Ishikawa H, Morimoto K, Ishihara R, Narahara H, Akedo I, Ioka T, Kaji I, Fukuda S (2004).",
"\"\"Reduction in salivary cortisol level by music therapy during colonoscopic examination\"\".",
"Hepato-Gastroenterology.",
"51 (56): 451–3.",
"PMID 15086180.^ Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C (October 2005).",
"\"\"Cortisol decreases and serotonin and dopamine increase following massage therapy\"\".",
"The International Journal of Neuroscience.",
"115 (10): 1397–413.",
"doi: 10.1080/00207450590956459.",
"PMID 16162447.^ Berk LS, Tan SA, Berk D (2008).",
"\"\"Cortisol and Catecholamine stress hormone decrease is associated with the behavior of perceptual anticipation of mirthful laughter\"\".",
"The FASEB Journal.",
"22 (1): 946.11.^ Hellhammer J, Fries E, Buss C, Engert V, Tuch A, Rutenberg D, Hellhammer D (June 2004).",
"\"\"Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress\"\".",
"Stress.",
"7 (2): 119–26.",
"doi: 10.1080/10253890410001728379.",
"PMID 15512856.^ Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R (July 2008).",
"\"\"The effects of phosphatidylserine on endocrine response to moderate intensity exercise\"\".",
"Journal of the International Society of Sports Nutrition.",
"5: 11. doi: 10.1186/1550-2783-5-11.",
"PMC 2503954.",
"PMID 18662395.^ Steptoe A, Gibson EL, Vuononvirta R, Williams ED, Hamer M, Rycroft JA, Erusalimsky JD, Wardle J (January 2007).",
"\"\"The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial\"\".",
"Psychopharmacology.",
"190 (1): 81–9.",
"doi: 10.1007/s00213-006-0573-2.",
"PMID 17013636.^ \"\"medicalnewstoday\"\".",
"Retrieved 25 September 2013.^ Quiroga MC, Bongard S, Kreutz G (July 2009).",
"\"\"Emotional and Neurohumoral Responses to Dancing Tango Argentino: The Effects of Music and Partner\"\".",
"Music and Medicine.",
"1 (1): 14–21.",
"doi: 10.1177/1943862109335064.^ Chandrasekhar K, Kapoor J, Anishetty S (July 2012).",
"\"\"A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults\"\".",
"Indian Journal of Psychological Medicine.",
"34 (3): 255–62.",
"doi: 10.4103/0253-7176.106022.",
"PMC 3573577.",
"PMID 23439798.^ Silverman MN, Pearce BD, Biron CA, Miller AH (2005).",
"\"\"Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection\"\".",
"Viral Immunology.",
"18 (1): 41–78.",
"doi: 10.1089/vim.2005.18.41.",
"PMC 1224723.",
"PMID 15802953.^ Lovallo WR, Farag NH, Vincent AS, Thomas TL, Wilson MF (March 2006).",
"\"\"Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women\"\".",
"Pharmacology Biochemistry and Behavior.",
"83 (3): 441–7.",
"doi: 10.1016/j.pbb.2006.03.005.",
"PMC 2249754.",
"PMID 16631247.^ Leproult R, Copinschi G, Buxton O, Van Cauter E (October 1997).",
"\"\"Sleep loss results in an elevation of cortisol levels the next evening\"\".",
"Sleep.",
"20 (10): 865–70.",
"PMID 9415946.^ Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M (February 1999).",
"\"\"Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes\"\".",
"International Journal of Sports Medicine.",
"20 (2): 128–35.",
"doi: 10.1055/s-2007-971106.",
"PMID 10190775.^ Fuqua JS, Rogol AD (July 2013).",
"\"\"Neuroendocrine alterations in the exercising human: implications for energy homeostasis\"\".",
"Metabolism.",
"62 (7): 911–21.",
"doi: 10.1016/j.metabol.2013.01.016.",
"PMID 23415825.",
"Cortisol has wide-ranging effects, including alterations of carbohydrate, protein, and lipid metabolism; catabolic effects on skin, muscle, connective tissue, and bone; immunomodulatory effects; blood pressure and circulatory system regulation; and effects on mood and central nervous system function.",
"In the short term, activation of the HPA axis in response to stress is adaptive.",
"However, long-term stress promoting chronic exposure of tissues to high cortisol concentrations becomes maladaptive.",
"...",
"Exercise, particularly sustained aerobic activity, is a potent stimulus of cortisol secretion.",
"The circulating concentrations of cortisol are directly proportional to the intensity of exercise as measured by oxygen uptake.",
"As is the case for the GH/IGF-1 and HPG axes, the HPA axis also receives many other inputs, including the light/dark cycle, feeding schedules, immune regulation, and many neurotransmitters that mediate the effects of exercise and physical and psychic stress [52].",
"...",
"The HPA is activated by stress, whether physical (exercise) or psychological.",
"Increased cortisol production, along with activation of the sympathetic nervous system, affects whole body metabolism.",
"This is apparently part of the catabolic response of the entire organism, with the purpose of mobilizing metabolic fuels that are subsequently broken down to produce energy and to dampen the threat or perceived threat.",
"...",
"Thus, a negative net energy balance leads to activation of the HPA axis and the circulating concomitants of the catabolic state in an attempt to keep core processes functional, realizing that the stress of exercise has no effect on cortisol and circulating metabolic substrates beyond the impact of the exercise energy expenditure on energy availability [60].",
"Thuma et al.",
"[61] had already made the important observation that the reported differences in cortisol levels pre- and postexercise depended on whether this difference was measured from a single pretest level or from the physiologic circadian baseline as determined in an independent session in the resting state.",
"By this analytical technique, these investigators showed that increasing energy expenditure led to significant cortisol release.",
"This release was apparent if they subtracted the physiologic circadian baseline from the postexercise value.^ Shalev I, Lerer E, Israel S, Uzefovsky F, Gritsenko I, Mankuta D, Ebstein RP, Kaitz M (April 2009).",
"\"\"BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions\"\".",
"Psychoneuroendocrinology.",
"34 (3): 382–8.",
"doi: 10.1016/j.psyneuen.2008.09.017.",
"PMID 18990498.^ Smith JL, Gropper SA, Groff JL (2009).",
"Advanced nutrition and humanmetabolism.",
"Belmont, CA: Wadsworth Cengage Learning.",
"p. 247.",
"ISBN 0-495-11657-2.^ Stimson RH, Andersson J, Andrew R, Redhead DN, Karpe F, Hayes PC, Olsson T, Walker BR (January 2009).",
"\"\"Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans\"\".",
"Diabetes.",
"58 (1): 46–53.",
"doi: 10.2337/db08-0969.",
"PMC 2606892.",
"PMID 18852329.^ Haas VK, Kohn MR, Clarke SD, Allen JR, Madden S, Müller MJ, Gaskin KJ (April 2009).",
"\"\"Body composition changes in female adolescents with anorexia nervosa\"\".",
"The American Journal of Clinical Nutrition.",
"89 (4): 1005–10.",
"doi: 10.3945/ajcn.2008.26958.",
"PMID 19211813.^ Brummett BH, Kuhn CM, Boyle SH, Babyak MA, Siegler IC, Williams RB (January 2012).",
"\"\"Cortisol responses to emotional stress in men: association with a functional polymorphism in the 5HTR2C gene\"\" (PDF).",
"Biological Psychology.",
"89 (1): 94–8.",
"doi: 10.1016/j.biopsycho.2011.09.013.",
"PMC 3245751.",
"PMID 21967853.^ Ceballos NA, Sharma S, Patterson TL, Graham R, Howard K (November 2015).",
"\"\"Stress, Immune Function and Collegiate Holiday Drinking: A Pilot Study\"\".",
"Neuropsychobiology.",
"72 (1): 8–15.",
"doi: 10.1159/000438757.",
"PMID 26304312.^ Häggström, Mikael; Richfield, David (2014).",
"\"\"Diagram of the pathways of human steroidogenesis\"\".",
"Wiki Journal of Medicine.",
"1 (1).",
"doi: 10.15347/wjm/2014.005.",
"ISSN 2002-4436.^ Willett LB, Erb RE (January 1972).",
"\"\"Short term changes in plasma corticoids in dairy cattle\"\".",
"Journal of Animal Science.",
"34 (1): 103–11.",
"doi: 10.2527/jas1972.341103x.",
"PMID 5062063.^ Margioris AN, Tsatsanis C (2011).",
"\"\"ACTH Action on the Adrenal\"\".",
"In Chrousos G. Adrenal physiology and diseases.",
"Endotext.org.^ Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM (October 2004).",
"\"\"11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response\"\".",
"Endocrine Reviews.",
"25 (5): 831–66.",
"doi: 10.1210/er.2003-0031.",
"PMID 15466942.^ van Staaveren, N., Teixeira, D. L., Hanlon, A. and Boyle, L. A.",
"(2015).",
"\"\"The effect of mixing entire male pigs prior to transport to slaughter on behaviour, welfare and carcass lesions\"\".",
"PLo S One.",
"10 (4): e0122841.",
"Bibcode: 2015PLo SO..1022841V.",
"doi: 10.1371/journal.pone.0122841.",
"PMC 4382277.",
"PMID 25830336.^ van Staaveren N, Teixeira DL, Hanlon A, Boyle LA (1997).",
"\"\"The effect of mixing entire male pigs prior to transport to slaughter on behaviour, welfare and carcass lesions\"\".",
"PLo S One.",
"10 (4): e0122841.",
"Bibcode: 2015PLo SO..1022841V.",
"doi: 10.1371/journal.pone.0122841.",
"PMC 4382277.",
"PMID 25830336.^ Schalke E, Stichnoth J, Ott S, Jones-Baade R (2007).",
"\"\"Clinical signs caused by the use of electric training collars on dogs in everyday life situations\"\".",
"Applied Animal Behaviour Science.",
"105 (4): 369–380.",
"doi: 10.1016/j.applanim.2006.11.002.^ a b Accorsi PA, Carloni E, Valsecchi P, Viggiani R, Gamberoni M, Tamanini C, Seren E (January 2008).",
"\"\"Cortisol determination in hair and faeces from domestic cats and dogs\"\".",
"General and Comparative Endocrinology.",
"155 (2): 398–402.",
"doi: 10.1016/j.ygcen.2007.07.002.",
"PMID 17727851.^ Möstl E, Messmann S, Bagu E, Robia C, Palme R (December 1999).",
"\"\"Measurement of glucocorticoid metabolite concentrations in faeces of domestic livestock\"\".",
"Zentralblatt für Veterinarmedizin.",
"Reihe A.",
"46 (10): 621–31.",
"PMID 10638300.",
"External links [ edit]Wikimedia Commons has media related to Cortisol.",
"Cortisol MS Spectrum Cortisol (serum/plasma) at Lab Tests Online Cortisol: analyte monograph – The Association for Clinical Biochemistry and Laboratory Medicine [ show]v t e Hormones [ show]v t e Endogenous steroids [ show]v t e Glucocorticoid receptor modulators [ show]v t e Mineralocorticoid receptor modulators Authority control LCCN: sh85063384 GND: 4160902-5Categories: Anxiety Glucocorticoids Otologicals Pregnanes Stress \""
] |
D2352580
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https://www.vetinfo.com/symptoms-hypoglycemia-dogs.html
|
Symptoms of Hypoglycemia in Dogs
|
Hypoglycemia is a condition also known as low blood sugar. The normal blood sugar in dogs is between 80 and 150 milligrams per deciliter (mg/dl) of blood. When the values fall below the normal values, the dog will suffer from hypoglycemia. The symptoms of hypoglycemia include shaking, seizures or even coma. It's important to recognize the symptoms of low blood sugar, so as to be able to administer glucose or sugar and prevent any complications. Causes of Low Blood Sugar in Dogs A low concentration of glucose in the blood may be caused by stress, low temperatures, poor nutrition or intestinal parasites that deprive the dog of the essential nutrients. Other less common causes include Addison's disease, tumors (especially those located on the pancreas), hormonal imbalances or fasting before strenuous activities. Juvenile hypoglycemia can occur in puppies less than 3 months of age, and some dog breeds are more affected. Young puppies don't have the ability to properly regulate their blood sugar and are also in need of glucose. Symptoms of Hypoglycemia The symptoms of low blood sugar will vary according to the severity of the glucose drop and the underlying cause. The most common signs of hypoglycemia include: Lack of appetite, which is due to a general weakness and the lack of energy Lethargy and sleepiness Shaking, which may be due to hypothermia; a dog that has a low glucose level will also have difficulty adjusting his body temperature and will be cold Twitching muscles Dilated pupils Behavioral changes; an active dog will suddenly become lethargic and uninterested Slow movements; the dog may have difficulty moving and a lack of coordination If the hypoglycemia is severe, the dog may suffer from seizures, temporary blindness and even coma. Diagnosing Hypoglycemia A diagnosis is needed to determine the cause of the low blood sugar and possibly prevent it in the future. The vet will perform a physical examination and will measure the blood glucose, and may run some other blood and urine tests. Treating Hypoglycemia If you notice any symptoms of low blood sugar, you should immediately administer 1 tbsp of honey or maple syrup to your pet. Make sure the pet ingests the honey or the syrup. If you place the honey under the dog's tongue or rub it on his gums, the sugar will get into the blood flow even faster. You should administer 1 tbsp of honey or syrup once every 6 hours, until the dog is stable. You should also visit the vet to determine the underlying cause and get suitable treatment. In cases of severe hypoglycemia when the dog has seizures, the vet may also administer intravenous injections with glucose. Your dog should live in a warm environment and when younger, you should provide extra blankets to prevent juvenile hypoglycemia. Get all the needed vaccinations and administer preventive de-wormers. Feed your dog quality food and according to the vet's guidelines. Feed him several times per day when he's a puppy and once or twice per day after he becomes an adult.
|
[
"Hypoglycemia is a condition also known as low blood sugar.",
"The normal blood sugar in dogs is between 80 and 150 milligrams per deciliter (mg/dl) of blood.",
"When the values fall below the normal values, the dog will suffer from hypoglycemia.",
"The symptoms of hypoglycemia include shaking, seizures or even coma.",
"It's important to recognize the symptoms of low blood sugar, so as to be able to administer glucose or sugar and prevent any complications.",
"Causes of Low Blood Sugar in Dogs A low concentration of glucose in the blood may be caused by stress, low temperatures, poor nutrition or intestinal parasites that deprive the dog of the essential nutrients.",
"Other less common causes include Addison's disease, tumors (especially those located on the pancreas), hormonal imbalances or fasting before strenuous activities.",
"Juvenile hypoglycemia can occur in puppies less than 3 months of age, and some dog breeds are more affected.",
"Young puppies don't have the ability to properly regulate their blood sugar and are also in need of glucose.",
"Symptoms of Hypoglycemia The symptoms of low blood sugar will vary according to the severity of the glucose drop and the underlying cause.",
"The most common signs of hypoglycemia include: Lack of appetite, which is due to a general weakness and the lack of energy Lethargy and sleepiness Shaking, which may be due to hypothermia; a dog that has a low glucose level will also have difficulty adjusting his body temperature and will be cold Twitching muscles Dilated pupils Behavioral changes; an active dog will suddenly become lethargic and uninterested Slow movements; the dog may have difficulty moving and a lack of coordination If the hypoglycemia is severe, the dog may suffer from seizures, temporary blindness and even coma.",
"Diagnosing Hypoglycemia A diagnosis is needed to determine the cause of the low blood sugar and possibly prevent it in the future.",
"The vet will perform a physical examination and will measure the blood glucose, and may run some other blood and urine tests.",
"Treating Hypoglycemia If you notice any symptoms of low blood sugar, you should immediately administer 1 tbsp of honey or maple syrup to your pet.",
"Make sure the pet ingests the honey or the syrup.",
"If you place the honey under the dog's tongue or rub it on his gums, the sugar will get into the blood flow even faster.",
"You should administer 1 tbsp of honey or syrup once every 6 hours, until the dog is stable.",
"You should also visit the vet to determine the underlying cause and get suitable treatment.",
"In cases of severe hypoglycemia when the dog has seizures, the vet may also administer intravenous injections with glucose.",
"Your dog should live in a warm environment and when younger, you should provide extra blankets to prevent juvenile hypoglycemia.",
"Get all the needed vaccinations and administer preventive de-wormers.",
"Feed your dog quality food and according to the vet's guidelines.",
"Feed him several times per day when he's a puppy and once or twice per day after he becomes an adult."
] |
D1551511
|
http://www.huffingtonpost.com/2013/01/21/inauguration-parade-2013-photos_n_2519552.html
|
Inauguration Parade 2013: Procession From Capitol To White House Up Pennsylvania Avenue Draws Crowds (PHOTOS)
|
WASHINGTON — While the swearing-in ceremony might have been the main draw for many on Inauguration Day, plenty of people turned out early along the Pennsylvania Avenue parade route between the Capitol and the White House. As Willie Geist of NBC News reported on Monday morning, some of the most sought-after spots were near the Navy Memorial at 7th Street NW, opposite the National Archives. It was around that location where President Obama and first lady Michelle Obama got out of their limousine and started walking along the processional route four years ago during the president’s first Inauguration. And sure enough, for their second Inauguration, the president and first lady left their limousine around 9th Street NW and walked for approximately three blocks before getting back in their motorcade. They arrived in the vicinity of the White House around 4:10 p.m. where they later gathered to watch the remainder of the Inauguration parade from the official review stand opposite Lafayette Park. The parade took a momentary pause as the first family, Vice President Biden and his family and their guests made their way into the review stand just before 4:45 p.m. Story continues after slideshow ... PHOTO GALLERYInauguration Parade 2013The parade was originally scheduled to start around 2:30 p.m. but was delayed by the Inauguration luncheon in the Capitol’s Statuary Hall, which was also behind schedule. The procession, which included 59 groups and 8,800 people, started to leave Capitol Hill around 3:15 p.m., went west along Constitution Avenue to Pennsylvania Avenue and ended at 17th Street NW and Pennsylvania Avenue near the White House. Among the groups featured in the parade were the 54th Massachusetts Volunteer Infantry Regiment, Boy Scout Troop 358 from Philadelphia, the Boston Crusaders Drum & Bugle Corps, the Georgia State University Marching Band, the Lesbian and Gay Band Association of St. Louis, Military Spouses of Michigan, the Navajo Nation Band of Arizona, New Mexico and Utah, the University of Maryland Mighty Sound Marching Band, the Virginia Military Institute Marching Unit and the Palmview High School Mariachi and Folkloric Group of La Joya, Texas, among many more. Some of the most recognized landmarks in the nation’s capital sit along the processional route. The president passed the U. S. Department of Labor, the Canadian Embassy, the Newseum, the National Gallery of Art, the Federal Trade Commission, the National Archives, the Navy Memorial, the FBI headquarters, the Justice Department, the Old Post Office Pavilion, Freedom Plaza, the John A. Wilson Building and the Treasury Department, among other buildings, memorials and statues. There were some protesters along the route, including members of the Westboro Baptist Church, who received a permit to demonstrate at John Marshall Park near 4th Street NW and Pennsylvania Avenue. At the John A. Wilson Building, the seat of the District of Columbia government, local officials had a protest banner on full display decrying the lack of full and equal congressional representation for residents of the nation’s capital. This post has been updated ...
|
[
"WASHINGTON — While the swearing-in ceremony might have been the main draw for many on Inauguration Day, plenty of people turned out early along the Pennsylvania Avenue parade route between the Capitol and the White House.",
"As Willie Geist of NBC News reported on Monday morning, some of the most sought-after spots were near the Navy Memorial at 7th Street NW, opposite the National Archives.",
"It was around that location where President Obama and first lady Michelle Obama got out of their limousine and started walking along the processional route four years ago during the president’s first Inauguration.",
"And sure enough, for their second Inauguration, the president and first lady left their limousine around 9th Street NW and walked for approximately three blocks before getting back in their motorcade.",
"They arrived in the vicinity of the White House around 4:10 p.m. where they later gathered to watch the remainder of the Inauguration parade from the official review stand opposite Lafayette Park.",
"The parade took a momentary pause as the first family, Vice President Biden and his family and their guests made their way into the review stand just before 4:45 p.m. Story continues after slideshow ... PHOTO GALLERYInauguration Parade 2013The parade was originally scheduled to start around 2:30 p.m. but was delayed by the Inauguration luncheon in the Capitol’s Statuary Hall, which was also behind schedule.",
"The procession, which included 59 groups and 8,800 people, started to leave Capitol Hill around 3:15 p.m., went west along Constitution Avenue to Pennsylvania Avenue and ended at 17th Street NW and Pennsylvania Avenue near the White House.",
"Among the groups featured in the parade were the 54th Massachusetts Volunteer Infantry Regiment, Boy Scout Troop 358 from Philadelphia, the Boston Crusaders Drum & Bugle Corps, the Georgia State University Marching Band, the Lesbian and Gay Band Association of St. Louis, Military Spouses of Michigan, the Navajo Nation Band of Arizona, New Mexico and Utah, the University of Maryland Mighty Sound Marching Band, the Virginia Military Institute Marching Unit and the Palmview High School Mariachi and Folkloric Group of La Joya, Texas, among many more.",
"Some of the most recognized landmarks in the nation’s capital sit along the processional route.",
"The president passed the U. S. Department of Labor, the Canadian Embassy, the Newseum, the National Gallery of Art, the Federal Trade Commission, the National Archives, the Navy Memorial, the FBI headquarters, the Justice Department, the Old Post Office Pavilion, Freedom Plaza, the John A. Wilson Building and the Treasury Department, among other buildings, memorials and statues.",
"There were some protesters along the route, including members of the Westboro Baptist Church, who received a permit to demonstrate at John Marshall Park near 4th Street NW and Pennsylvania Avenue.",
"At the John A. Wilson Building, the seat of the District of Columbia government, local officials had a protest banner on full display decrying the lack of full and equal congressional representation for residents of the nation’s capital.",
"This post has been updated ..."
] |
D88655
|
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673862/
|
Spiralian gastrulation: germ layer formation, morphogenesis, and fate of the blastopore in the slipper snail Crepidula fornicata
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Evo Devo. 2015; 6: 24. Published online 2015 Jun 24. doi: 10.1186/s13227-015-0019-1PMCID: PMC4673862Spiralian gastrulation: germ layer formation, morphogenesis, and fate of the blastopore in the slipper snail Crepidula fornicata Deirdre C. Lyons, Kimberly J. Perry, and Jonathan Q. Henry Author information ► Article notes ► Copyright and License information ►This article has been cited by other articles in PMC. Go to: Abstract Background Gastrulation is a critical step in bilaterian development, directly linked to the segregation of germ layers, establishment of axes, and emergence of the through-gut. Theories about the evolution of gastrulation often concern the fate of the blastopore (site of endomesoderm internalization), which varies widely in a major branch of bilaterians, the Spiralia. In this group, the blastopore has been said to become the mouth, the anus, both, or neither. Different developmental explanations for this variation exist, yet no modern lineage tracing study has ever correlated the position of cells surrounding the blastopore with their contribution to tissues of the mouth, foregut, and anus in a spiralian. This is the first study to do so, using the gastropod Crepidula fornicata. Results Crepidula gastrulation occurs by epiboly: the first through third quartet micromeres form an epithelial animal cap that expands to cover vegetal endomesodermal precursors. Initially, descendants of the second and third quartet micromeres (2a–2d, 3a–3d) occupy a portion of the blastopore lip. As the blastopore narrows, the micromeres’ progeny exhibit lineage-specific behaviors that result in certain sublineages leaving the lip’s edge. Anteriorly, cells derived from 3a 2 and 3b 2 undergo a unique epithelial-to-mesenchymal transition involving proliferation and a collective movement of cells into the archenteron. These cells make a novel spiralian germ layer, the ectomesoderm. Posteriorly, cells derived from 3c 2 and 3d 2 undergo a form of convergence and extension that involves zippering of cells and their intercalation across the ventral midline. During this process, several of these cells, as well as the 2d clone, become displaced posteriorly, away from the blastopore. Progeny of 2a-2c and 3a-3d make the mouth and foregut, and the blastopore becomes the opening to the mouth. The anus forms days later, as a secondary opening within the 2d 2 clone, and not from the classically described “anal cells”, which we identify as the 3c 221 and 3d 221 cells. Conclusions Our analysis of Crepidula gastrulation constitutes the first description of blastopore lip morphogenesis and fates using lineage tracing and live imaging. These data have profound implications for hypotheses about the evolution of the bilaterian gut and help explain observed variation in blastopore morphogenesis among spiralians. Electronic supplementary material The online version of this article (doi:10.1186/s13227-015-0019-1) contains supplementary material, which is available to authorized users. Keywords: Spiralia, Lophotrochozoa, Blastopore, Ectomesoderm, Endomesoderm, Epiboly, Gastrulation, Amphistomy Go to: Background Gastrulation accomplishes several tasks that are critical for metazoan development, most importantly the segregation of germ layers and re-arrangement of cells to form the basic body-plan [ 1 ]. Germ layer segregation occurs when ectodermal, endodermal, and mesodermal cells adopt distinct gene regulatory states; morphogenetic events internalize endodermal and mesodermal cell types. Because the basic body-plan is often established by the end of gastrulation, theories explaining body-plan evolution often suggest that body-plan divergence was driven in part by modifications to gastrulation events themselves (e.g., [ 2 – 5] and references therein). For example, several evolutionary theories concern the site of gastrulation, a transient embryonic location where endoderm and mesoderm are internalized, called the blastopore [ 2, 3, 5 – 7 ]. The fate of the blastopore was traditionally used as a character for building taxonomic trees, separating protostomes (in which the blastopore becomes the opening to the mouth) from deuterostomes (in which the mouth forms separately from the blastopore, and the latter often becomes the anus) (reviewed in [ 2, 6 – 8 ]). Although the terms deuterostome and protostome are still in our vernacular, they have lost much of their phylogenetic significance because cladistic analyses based on molecular characters (which are independent of morphology) show that protostomy and deuterostomy are not a reliable diagnostic character for major clades of bilaterians. Deuterostomy appears to be ancestral for the Ambulacaria and Chordata [ 1, 9 ], but among the groups traditionally thought to belong to a protostome branch—the Ecdysozoa and Spiralia (which includes the Lophotrochozoa)—the fate of the blastopore is more complex and variable [ 7, 10, 6, 11 ]. Depending on the species, the blastopore has been reported to become the mouth (protostomy), the anus (deuterostomy), both mouth and anus (amphistomy), or neither (i.e., the blastopore closes). Debate remains about how this diversity in blastopore fate arose, whether the differences have any influence on body-plan divergence, and even if the blastopore can be properly homologized between distantly related animals [ 2, 5, 7, 8, 10, 12, 13 ]. To resolve these debates, it is necessary to compare gastrulation in multiple species, in the context of a solid phylogenetic framework. Spiralian lophotrochozoans offer a means to address many of these questions because although the fate of the blastopore varies between species, they share a stereotyped early cleavage pattern and fate map [ 14, 15 ]. These attributes make it possible to identify unambiguously homologous cell lineages, allowing direct comparison of cells around the blastopore. Yet, few modern studies have leveraged spiralians’ unique strengths for investigating gastrulation [ 16 – 19 ]. Here, we study gastrulation in a representative spiralian species, the slipper snail Crepidula fornicata. The Spiralia is a large and morphologically diverse assemblage of roughly 14 phyla [ 20, 21, 15 ]. Many members of this group, including annelids, molluscs, platyhelminthes, and nemerteans, exhibit a highly conserved pattern of embryonic cell divisions termed “spiral cleavage” [ 15, 14 ]. The fate map, birth order, and geometry of cells are so conserved between these animals that it is possible to compare homologous lineages, with single-cell resolution, between spiralians with vastly different larval and adult morphologies. During gastrulation, spiralians transition from the highly conserved spiralian cleavage program to their species-specific body-plans. Thus, spiralians are an excellent group for testing if there is indeed a relationship between varying gastrulation modes (e.g., the fate of the blastopore) and body-plan evolution. Furthermore, because spiral cleavage is considered ancestral for the Spiralia as a whole [ 14 ], studying gastrulation in these species can inform us about how gastrulation, and body-plans, might have evolved in metazoans. The blastopore is important to these arguments because, typically, it is ontogenetically linked to the openings of the digestive tract [ 2, 5, 7, 8, 10, 22, 23 ]. For example, in anthozoan cnidarians and ctenophores, the blastopore forms at the embryonic animal pole and matures into a dual-function, single orifice for feeding and excretion [ 24 ]. In deuterostomes, the blastopore forms at the vegetal pole and matures into the anus, while the mouth forms later, at a separate site within ventral anterior ectoderm [ 9 ]. Among the Ecdysozoa and Spiralia, the blastopore also forms at the vegetal pole, but its subsequent morphogenesis and fate is more complex and variable [ 6 – 8, 10, 12, 25 – 28 ], complicating discussions about the ancestral mode of gastrulation in these groups. Compounding this problem is the fact that most of the work on spiralian gastrulation is based on classical descriptions from over 100 years ago [ 5, 7, 8, 29 ], long before intracellular lineage tracing or time-lapse imaging were possible. The accuracy of these original descriptions comes into question, especially when concerning with the relationship between the blastopore and the formation of the mouth and anus; both can form days after the blastopore exists, making it very difficult to follow cell clones without modern intracellular lineage tracing. Only a few previous lineage tracing studies have examined gastrulation in spiralians, most notably in the leech Helobdella robusta [ 16 ], and in the snail Ilyanassa obsoleta [ 18 ]. However, these studies did not focus on the behavior or fate of the blastopore per se. The slipper snail C. fornicata is an emerging model system for developmental and evolutionary studies in spiralians [ 30 – 34 ]. Previously, a fate map was generated for every cell present in the four-principle quartets of animal micromeres, and the vegetal macromeres, for their respective contributions to the tissues of the veliger larva [ 31 ]. Here, we used lineage tracing, and time-lapse imaging, to present the first detailed examination of germ layer formation and morphogenesis of cells surrounding the blastopore during gastrulation in Crepidula. Gastrulation occurs by epiboly, as animal cap micromeres expand to cover vegetal territories. Later, the vegetal endodermal cells re-arrange to form a cavity that becomes part of the embryonic digestive tract, the archenteron. To make it possible to directly homologize gastrulation events between species, we distinguish between the blastopore and blastopore lip. At early epiboly stages, we define the blastopore as the endoderm/mesoderm cells themselves, and later as the hole/lumen of the archenteron. We define the blastopore lip as those cells that give rise exclusively to ectodermal cells that are initially in direct contact with the endodermal/endomesodermal cells. Here, we document specific lineage contributions to the anterior and posterior ends of the digestive tract (including mouth, foregut, and anus), which are derived from cells of the second and third quartet micromeres that occupied the blastopore lip. In addition, we found that ectomesoderm arises from specific third quartet cells (3a 2 and 3b 2) that are situated at the anterior blastopore and become internalized by an epithelial to mesenchymal transition. During gastrulation, blastopore lip cells exhibit extensive cell re-arrangement. The posterior lip of the blastopore closes by a form of convergence and extension that involves zippering of cells derived from the third quartet (from 3c 2 and 3d 2 ). The cells that undergo convergence and extension give rise to a line of ciliated ectodermal cells along the ventral midline, which we argue includes cells akin to the neurotroch and telotroch described in other spiralians. The two posterior-most ciliated cells derived from these clones on the ventral midline were classically described by Conklin [ 34] as the “anal cells.” However, we found that these cells do not give rise to the anus, and so we renamed them the “terminal cells.” The anus arises from progeny of 2d 2, and as a result of convergence and extension, these cells become excluded from the posterior blastopore lip. The anus thus forms from a secondary opening, and not from the blastopore, at 12 days of development. The blastopore becomes the opening to the mouth. We discuss the implications of these results for debates about the evolution of the blastopore in metazoans. Go to: Methods Animal care and handling Stacks of adult C. fornicata were obtained from the Marine Resources Department at the Marine Biological Laboratory (Woods Hole, MA. USA). Adults were obtained from local waters by dredging during late winter months (January to March) and maintained in cold running seawater at approximately 12 °C to prevent egg laying. The gravid females are stimulated to lay eggs by transferring them to warm water sea tables at 18–22 °C, as needed throughout the summer. Embryos were obtained and reared, as previously described [ 30 – 34 ]. Briefly, the de-capsulated eggs and embryos were raised at room temperature (approx. 20 °C) in gelatin-coated Petri dishes containing 0.2-μm-filtered seawater with penicillin (100 U/ml, Sigma, St Louis, MO) and streptomycin sulfate (200μg/ml, Sigma, St Louis, MO). Lineage tracing Specific cells were pressure microinjected with fluorescent lineage tracers, as previously detailed, to follow their contributions to specific germ layers, the blastopore, mouth, foregut, and anus (Rhodamine Green Dextran, cat # D-7153, or Di IC18 (3), cat # D-282, Life Technologies, Grand Island, NY; [ 31, 33 – 36 ]. In some cases, multiple cells were injected, and sub-lineages were followed, by sequential injection of two cells with these different tracers. All second and third quartet micromeres (Fig. 1a – h; Additional file 11: Figure S1) were individually microinjected to follow their behavior during the process of gastrulation (Figs. 2, Additional file 12: Figure S2; S2;3, 3, Additional file 13: Figure S3; S3;4, 4, Additional file 14: Figure S4;S4;5, 5, Additional file 15: Figure S6; S6;6, 6, Additional file 16: Figure S6; S6;7, 7, Additional file 17: Figure S7; S7;8, 8, Additional file 18: Figure S8; S8;9,Additional 9 ,Additional file 19: Figure S9; S9;10, 10, Additional file 20: Figure S10; S10;11, 11, Additional file 21: Figure S11; and and12, 12, Additional file 22: Figure S12;) and their contributions to the formation of various germ tissues and the gut (Figs. 13, Additional file 23: Figure S13; S13;14, 14, Additional file 24: Figure S14; and and15, 15, Additional file 25: Figure S15). For each micromere, the two daughter cells (i.e., 2a 1 and 2a 2 or 3a 1 and 3a 2 cells) were also labeled independently (a total of 16 sub-lineages; Figs. 14 and and15). 15 ). A minimum of five embryos were scored, in the live embryo, for each clone examined, and these were all found to be highly regular. Fig. 1Early epiboly and position of clones at the blastopore lip. a–h Cartoons of early embryo with second and third quartet micromeres colored, as indicated in key to the right. a–c Animal pole views; d is a ventral/vegetal view; e–h ... Fig. 2Narrowing of the blastopore during later epiboly, and formation of the mouth/stomodeum. a–e Confocal images of living embryos expressing UTPH-GFP to mark the actin cytoskeleton, and histone H2B-RFP to mark the nuclei. Ventral views are shown during ... Fig. 3Fates of micromere 2a, and its subclones, during gastrulation and organogenesis. Images of live embryos with dextran- and di I-labeled 2a, or 2a subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 4Fates of micromere 2b, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 2b, or 2b subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 5Fates of micromere 2c, and its subclones, during gastrulation and organogenesis. Images of live embryos with dextran and di I labeled 2c, or 2c subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 6Fates of micromere 2d, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 2d, or 2d subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 7Fates of micromere 3a, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3a, or 3a subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 8Fates of micromere 3b, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3b, or 3b subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 9Behavior of ectomesoderm (3a 2, 3b 2). a–i Time-lapse movie of an embryo injected with utrophin-GFP (UTPH) to mark cell outlines, and histone H2B-RFP (H2B) to mark nuclei, where indicated. Ventral view. bp blastopore. Several unidentified (x) daughter ... Fig. 10Fates of micromere 3c, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3c, or 3c subclones, as indicated. Animal pole is up in a and b. Anterior is up in c–t. a, b Dorso-lateral ... Fig. 11Fates of micromere 3d, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3d, or 3d subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent ... Fig. 12Behavior of posterior blastopore lip cells undergoing convergence and extension (3c 2, 3d 2 ). a–aa Projected confocal Z slices of embryos injected with dextran or di I, into 3c, 3d or their subclones, as indicated. a Ventral view of an embryo at ... Fig. 13Origin of the anus (2d 2). Images of live embryos, with dextran and di I-labeled 4d, 3d, 3c, 2d, or 2d subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion protein for the actin-binding domain ... Fig. 14Summary of second and third quartet clones. Columns show clones, colored as labeled, and according to those shown in Figs. 1 and and15. 15. Rows show time points as indicated at the far right. Top row shows animal views; all other rows ... Fig. 15Lineage diagram of second and third quartet micromeres and third quartet macromeres. Colors correspond to those given in Figs. 1 andand14 14Fluorescently tagged protein expression To help distinguish individual cells and their nuclei in live embryos, we microinjected synthetic m RNAs to express various combinations of fluorescently tagged proteins (Fig. 1 ). None of the constructs used contain Crepidula -specific sequence, yet they are expressed robustly, and fluorescence was detected within a few hours of injection. DNA in the nuclei was followed using histone H2B-RFP (H2B-RFP) and histone H2B-GFP (H2B-GFP) fusions, while plasma membrane was followed with an RFP-membrane fusion (MEM-GFP). These clones were the gift of the Mc Clay lab, Duke University [ 37 ]. We followed live F-actin using a GFP fusion of the actin-binding domain of utrophin (UTPH-GFP) and live microtubules using GFP or RFP fusions of the MT binding domain of ensconsin (EMTB-3x GFP). These clones were the gift of the Bement Lab (University of Wisconsin) [ 38, 39] and are now available commercially ( https://www.addgene.org/26737/; https://www.addgene.org/26741/ ). Synthetic m RNAs were generated from linearized plasmids using the m Message m Machine kit (Life Technologies, Grand Island, NY) and purified with RNeasy Min Elute Cleanup kit (Qiagen, Valencia, CA). Stock concentrations of these individual m RNAs ranged from 1 to 2 μg/μl in RNAse-free sterile d H 2 O. RNAs were diluted to a working concentration of 300–500 μg/μl. To visualize the solutions as they were being injected, the RNAs were mixed with a sterile filtered RNAse-free solution of 0.5 % phenol red, (1 part phenol red solution, cat. #P0292, Sigma, St Louis, MO, to 2 or 3 parts RNA solution). In this manner, a faint red cloud can be visualized inside the zygote during injection. Synthetic m RNAs were microinjected into fertilized eggs prior to first cleavage and approximately 5–10 % of the cell’s volume was injected. When the fertilized eggs are first collected, it is not possible to know exactly when first cleavage will take place. If the injections are carried out too soon before first cleavage, some graded/mosaic level of expression may be noted at later stages. The latter cases were not used for further study. Visible levels of expression can first be detected under a fluorescence dissecting scope around the four- to eight-cell stages. Fixation and histology Embryos and larvae were fixed in a 3.7 % solution of ultrapure formaldehyde (made using the manufacturer’s 10 % stock solution, Ted Pella, Inc., Redding, CA, USA) dissolved in FSW with added Instant Ocean Aquarium Sea Salt Mixture (United Pet Group, Blacksburg, VA, USA) to adjust for the reduced osmolarity (0.47 gm added per 50 ml of final working volume). Embryos were fixed for 1 h at room temperature and rinsed three times in sterile 1× PBS (1× PBS:1.86m M Na H 2 PO 4, 8.41m M Na 2 HPO 4, 175m N Na Cl, p H 7.4), followed by three washes in 100 % methanol before storage at −80 °C. Acetylated tubulin antibody labeling (1:400, cat #T7451, Sigma, St. Louis) followed the method described in [ 40 ]. A solution of 0.5 μg/ml DAPI (Life Technologies, Grand Island, NY) dissolved in 1× PBS was applied to embryos following antibody labeling to visualize nuclei. Embryos were incubated in the dark for 10 min, followed by three washes in 1× PBS/0.1 % Tween, and stored in 80 % glycerin/20 % 1× PBS at 4 °C until imaging. Microscopy Live embryos expressing fusion proteins, or labeled with traditional lineage tracers (di I or dextrans), were mounted in filtered seawater between Rain-X-coated (ITW Global Brands, Houston, TX) glass slides and coverslips supported by tiny clay feet (Van Aken Plastalina, Rancho Cucamonga, CA, USA). For long-term time-lapse imaging, the coverslips were sealed with molten VALAP to prevent desiccation [ 41 ]. For time-lapse, embryos were imaged every 5–10 min for anywhere from 4 to 48 h. Widefield images were captured with a Zeiss Axio Imager 2 (Carl Zeiss Inc., Munich, Germany). Scanning confocal imaging was carried out with an inverted Zeiss LSM 700, Zeiss LSM 780, and Zeiss Cell Observer spinning disc microscopes (Carl Zeiss Inc., Munich, Germany). Light sheet imaging was carried out with a Zeiss Light Sheet. Z1 (Carl Zeiss Inc., Munich, Germany). For image processing, Z-stacks were prepared to make maximum projections with Fiji and Image J software (National Institutes of Health, Bethesda, MD, USA) or the focus stacking software Helicon Focus (Helicon Soft Ltd., Kharkov, Ukraine). Fixed embryos labeled with antibodies were placed on Rain-X-coated (ITW Global Brands, Houston, TX) glass slides in 80 % glycerol/20 % 1× PBS. Coverslips were first prepared with small supporting feet made from plastic “Tough Spots” adhesive labels (Diversified Biotech, Boston, MA, USA). These adhesive labels were trimmed into 1–2-mm squares, stacked three layers thick, and adhered to the four corners of glass coverslips to prevent the embryos from being crushed. Specimens were visualized on a Zeiss Axioplan microscope (Carl Zeiss Inc., Munich, Germany), and imaging was conducted with a Spot Flex camera (Spot Imaging Solutions, Sterling Heights, Michigan). Image stacks were combined and flattened using Helicon Focus (see above). Go to: Results Behavior of cells during cleavage and early epiboly Early development in Crepidula has been described by Conklin [ 42] and Hejnol et al. [ 31] (see also [ 30 ]). The fertilized egg undergoes two rounds of orthogonal, equal cleavage occurring parallel to the animal-vegetal axis, giving rise to four blastomeres (macromeres) founding embryonic quadrants A, B, C, and D. These macromeres undergo several rounds of highly asymmetric cleavages that give rise to four tiers of smaller micromere quartets (“q”) at the animal pole: 1a–1d (1q), 2a–2d (2q), 3a–3d (3q), and 4a–4d (4q) (Fig. 1a–h; Table 1 ). As each micromere quartet is born, the sister quartets’ vegetal macromeres (“Q”) are renamed: 1A–1D (1Q); 2A–2D (2Q); 3A–3D (3Q), and 4A–4D (4Q). The embryo is radially symmetric up through the early 24-cell-stage (when the first three quartets have been born). Symmetry is broken at approximately 27 h past fertilization (hpf) at 20 °C, when the 3D macromere divides precociously, giving rise to the 4d micromere at the 25-cell stage (Fig. 1a ). At approximately 33 hpf, 4d divides bilaterally to form left and right teloblasts (ML and MR) which produce endoderm and mesoderm (“endomesoderm,” Fig. 1b ). Table 1Crepidula fornicata staging system A fate map of these teloblasts has recently been established up through their fifth division [ 34 ]. Thus, the well-defined cleavage pattern of the 4d lineage can be used to quickly orient the embryo during early, spherical or “round” stages of gastrulation (Fig. 1; Table 1 ). We found that some fluorescent biosensors, particularly actin (Fig. 1q) and membrane sensors (Fig. 1t ), appear brightest in the 4d lineage and thus can be used to assess the age and orientation of embryos, even in the absence of specific cells being directly labeled. The 4d micromere is born as a tear-shaped cell with its pointed end directed towards the center of the embryo, which is covered by the micromere cap (Fig. 1a–i ). The rounded end is initially exposed at the surface of the embryo, as it is not yet covered fully by the micromere cap. All of its mesodermal derivatives, and some of its endodermal derivatives, will be born from the more pointed, internal end, and thus those cells are internalized at birth (Fig. 1k–q ). In contrast, the larger rounded, exposed area of the 4d cell is where the future 1m L/R and 3m L/R endodermal lineages will be born (Fig. 1c ). At first, the micromere cap does not fully cover these cells, but they will be covered during epiboly (99 hpf, Fig. 1c–d and o–q; Table 1 ). At approximately 47 hpf, the 3A–3C macromeres divide to form the 4a–4c micromeres (Table 1 ). Following this period of early cleavage divisions, the embryo undergoes compaction and assumes a tight spherical shape (Fig. 1k, p, r; Table 1 ). The micromere-derived animal cap gradually expands to cover more surface area (Fig. 1q–w ), and by 60 hpf, the animal cap covers 50–55 % of the spherical surface having reached its widest circumference at the equator of the embryo (Fig. 1r; Table 1 ). Cellular behavior during gastrulation: epiboly of the micromere cap While we do not fully understand the mechanisms that regulate expansion of the micromere cap, it likely involves continued cell divisions (Fig. 1s–w) and thinning of micromere cap progeny. As the animal cap expands, it covers more of the endomesodermal lineages (Figs. 1 and and2). 2 ). At 91 hpf, the spherical embryo begins to change shape as gastrulation continues to take place by the process of epiboly. At this time, the embryo begins to flatten noticeably along the animal-vegetal axis (Fig. 1h, ,p; p; Table 1 ). The edge of the cap (derived from the second and third quartet micromeres, the colored lineages in Fig. 1a–h) can just begin to be observed when viewed from the flattened vegetal pole, which can be seen in Fig. 2f. At this stage, the animal cap covers approximately 65 % of the surface of the embryo. Time-lapse movies of embryos expressing fluorescent membrane (MEM-RFP) or actin cytoskeleton (UTPH-GFP) biosensors did not show obvious lamellipodial or filopodial extensions during animal cap expansion (see Fig. 1s–w; Fig. 2f, and Additional files 1 and 2 ). This initial expansion of the micromere cap correlates with cell divisions in the epithelium (Fig. 1s–w ), which generates an increasingly larger number of smaller cells, and correlates with the flattening or thinning of this layer of cells (e.g., Fig. 1i, k, n, r, o, q ). After reaching the equator, the micromere cap begins to constrict towards the vegetal pole (Fig. 2 ), advancing over the 4Q macromeres and 4q micromeres for the next 50 h as the blastopore narrows (Fig. 2a–b and f–h; Table 1 ). During this process, the embryos become irregularly shaped as the internal macromeres and fourth quartet micromeres begin to undergo divisions (beginning at approximately 99 hpf; Fig. 2b, g, h ). At this time, the four macromeres divide equally, and Conklin [ 42] referred to this as the formation of a “fifth quartet.” Divisions are oriented such that the internal fourth quartet macromeres and micromeres ultimately assume a rectangular packing arrangement. The embryo then elongates, which begins by 117 hpf, and the embryo assumes a flattened rectangular shape (Fig. 2b, ,h; h; Additional files 3 and 4; Table 1 ). Throughout these stages, a noticeable depression, which becomes the embryonic gut or archenteron, can be seen at the site of the blastopore. By 120 hpf, the embryo has assumed a more rounded, short ellipsoidal form, with the elongated axis corresponding to the future anterior-posterior axis (Fig. 2c, ,h h – i ). The blastopore begins to be displaced towards the anterior end of the embryo by 141 hpf (Fig. 2d – e, ,i; i; Additional file 5 ). Most of the elongation appears to occur in the post-trochal region, and as a consequence, the blastopore is displaced in an anterior direction (Table 1 ). Though Conklin [ 42] reported that the blastopore temporarily closes deep within its recess, we have not observed this. Our observations indicate that an external opening persists throughout the process of gastrulation, and during this process, the macromeres can be seen within it. This opening ultimately becomes the mouth (Fig. 2d – e ). By elongation stages, gastrulation has been completed and the process of organogenesis begins to unfold (Table 1 ). Overt signs of organogenesis can be seen by 170 hpf, when the rudiments of the velar lobes, foot, and shell gland can be clearly seen (Figs. 3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, and and13). 13 ). After several more weeks, advanced veliger larvae hatch and enter the water column where they begin to feed and ultimately settle to undergo metamorphosis to form juvenile snails. The fates of cells around the blastopore Although a fate map was previously generated for each cell up through the 25-cell stage [ 31 ], those fates were related only to the tissues present within the veliger larvae. That preliminary work established the basic germ layer derivatives of those embryonic cells, but did not describe the behavior of lineages during gastrulation. In particular, we were interested in where these clones were situated relative to the blastopore. Thus, we labeled individual second and third quartet micromeres, and some of their progeny, and observed their behavior during gastrulation. We also followed their contributions to specific tissues, including the ectomesoderm and ectodermal components of the digestive tract, such as the mouth, esophagus, and the anus (Figs. 3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, ,13, 13, ,14, 14, and and15 15 ). Labeling individual clones was necessary to understand how cells behave near the blastopore. Lineage tracing results are described below for each of the 2q and 3q micromeres, as well as their immediate progeny 2q 1 /2q 2 and 3q 1 /3q 2, representing a total of 16 clones (Figs. 3, ,4, 4, ,5, 5,,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, ,13, 13, ,14, 14, and and15). 15 ). As specified by Conklin [ 42 ], the daughters situated in a clockwise position around the animal-vegetal axis (as viewed from the animal pole), or those located closer to the animal pole, carry the superscript 1 (e.g., 2a 1 ). Those situated in a counter-clockwise location, or situated closer to the vegetal pole, carry the superscript 2 (e.g., 2a 2 ). Individual clones are shown in Figs. 3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, and and13 13 for different developmental stages described in Table 1. A schematic diagram summarizing the relationships of these clones for six different stages of development between 18 and 145 hpf is also shown in Fig. 14. A lineage diagram showing the ultimate fate of these clones is also shown in Fig. 15. Time-lapse movies were also prepared to capture the dynamic behavior of certain cells (Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 ). These analyses influenced how we defined the blastopore in Crepidula. Definitions of “blastopore” can vary between animals, referring alternatively to the literal hole into which endoderm/mesoderm move, or to the endodermal and mesodermal cells themselves, or to cells surrounding the hole [ 2, 10, 13, 25 ]. To avoid confusion and enable direct comparisons with other species, we distinguish between the blastopore (the hole) and the cells surrounding that hole—which we call the blastopore lip (Fig. 16, Additional file 26: Figure S16). These definitions became necessary because of the nature of epiboly, since gastrulation begins when the ectodermal cap spreads over the macromeres, but it is not until later stages that the endodermal/mesodermal tissues themselves re-arrange to form an archenteron and a literal hole (Fig. 16; Table 1 ). Additionally, even after an obvious blastopore hole forms, the cells surrounding it change through cell rearrangement. Fig. 16Morphogenesis of the blastopore lip. a–e Vegetal/ventral views during gastrulation with the future anterior at the top of the figure. Time points are the same as those shown in rows 2–6 in Figs. 1 andand14: 14: a ~94 hpf, ... In Crepidula, during early stages of gastrulation, the blastopore consists of endodermal/endomesodermal precursors derived from the fourth quartet macromeres (4A-4D) and fourth quartet micromeres (4a-4cd) (Fig. 16a – b ); at later stages of gastrulation the blastopore is an actual hole/cavity leading inside of the embryo, and is surrounded by cells of the developing archenteron (Fig. 16c – e ). The blastopore lip is made up of progeny derived from each of the second and third quartet micromeres that give rise to ectoderm exclusively (Figs. 14 and and16, 16, dashed white line). This boundary between ectoderm and endoderm was defined through our detailed lineage analysis during gastrulation stages. For example, initially, we assumed that the edge of the micromere cap (colored cells in Fig. 1d) was exactly equivalent to the blastopore lip, but lineage tracing of the 3a and 3b cells showed that the 3a 2 and 3b 2 sublineages make mesoderm (Figs. 14 and and15), 15 ), and so we had to adjust our delineation of the blastopore lip to run between the 3a 2 /3a 1 and 3b 2 /3b 1 clones (compare Figs. 1d and 16a ). The second quartet (2a and 2c)All four of the second quartet micromeres give rise to progeny that lie along the lip of the blastopore (Fig. 14 ). After their first division, specific daughters of these cells mainly lie along the blastopore lip (2a 1, 2b 2, 2c 2, and 2d 1 and 2d 2 cells; Figs. 3a, ,5a, 5a, and and14). 14 ). 2a and 2c give rise to bilaterally symmetrical clones of ectodermal cells that extend to the left and right sides of the embryo, respectively (Figs. 3b – j and and5c 5c – j ). For the most part, their daughters, 2a 2 and 2c 1, make mirror symmetrical contributions to the development of the mouth (Figs. 3j, ,5j, 5j, ,14, 14, and and15). 15 ). Both of these cells also extend a long thin line of cells from the developing blastopore/mouth in a bilaterally symmetrical fashion, which generate the left and right secondary ciliary band (i.e., the metatroch; Figs. 3 and and5). 5 ). These cells also form much larger separated posterior, dorsolateral clones of cells located in the post-trochal region that also contribute to the shell gland/mantle (from both 2a 1, 2a 2 and 2c 1, 2c 2; Figs. 3h, k and 5i, q ). On the other hand, 2a 1 and 2c 2 make some slightly different contributions. Though both of these cells make contributions to the posterior, dorsolateral clones of cells located in the post-trochal region (Figs. 3h, m and 5i, s ), 2a 1 does not contribute to the mouth or esophagus (Fig. 3m ), while 2c 2 does (Fig. 5k ). Fine speckles of labeled material are also seen mainly on the right anterior side of the head, which are derived from the progeny of 2c (Fig. 5c – e, ,g, g, ,h h – l, ,o o – p ). These appear to be too small to be cells, and their identity is uncertain (see also [ 18 ]). Hejnol et al. [ 31] reported that ectoderm covering the left external kidney (absorptive cell) was derived from 2a; however, Lyons et al. [ 34] showed that this structure is derived from 4d and is directly exposed to the external environment. Hejnol et al. [ 31] also reported that some ectomesoderm is also derived from 2c. Specifically, they reported that the ectodermal covering of the larval heart and muscles of the heart are derived from 2c. Here, we find no evidence of any ectomesoderm being derived from 2c (Fig. 15 ). In fact, recently, we showed that the heart muscles are actually derived as endomesoderm from 4d [ 34 ]. Hejnol et al. [ 31] reported that 2a and 2c give rise to the left and right coverings of the statocysts, respectively, and to the pedal and apical ganglia, as well as the osphradium (the latter being derived from 2c, which we have not verified here). The second quartet (2b)Initially, 2b gives rise to a clone of ectodermal cells located along the very anterior edge of the blastopore (Figs. 4a and and14). 14 ). This clone gives rise to two wings, and later gives rise to bands that extend bilaterally to the sides of the embryo (Fig. 4a – j ). The right and left bands of cells are derived mainly from 2b 1 and 2b 2, respectively. A single ciliated cell derived from 2b 2 lies at the ventral midline at the very anterior (top) opening of the mouth (Fig. 4o – s ). An isolated group of 2–3 small rounded cells derived from 2b 1 also lie in the head anterior to the mouth (Fig. 4o – p, ,u u – w ). These cells presumably give rise to neural cells or may undergo cell death, as they become hard to identify in older embryos. 2b gives rise to ectoderm located anterior to the mouth. The bilaterally symmetrical bands of cells derived from 2b 1 and 2b 2 give rise to the ciliated food grooves (see also [ 31 ]), as well as some nerves in the head (Figs. 4q – y and and15). 15 ). As these bilateral bands extend further to the dorsal side, (Fig. 4k, ,l), l ), they eventually fuse along the dorsal midline (Fig. 4m, ,n). n ). Here, two large cells each derived from 2b 1 and 2b 2 detach from their sister cells and move posteriorly along the dorsal surface to give rise to part of the shell gland and mantle. As this occurs, those former cells appear to become depressed below the surface within the ectoderm compared to the surrounding cells. The bands of cells derived from 2b 1 and 2b 2 also expand to contribute to dorsal-lateral ectoderm adjacent to the head bulge (head vesicle, which is derived from the first quartet micromeres, not followed here). The dorsal-right lateral clone derived mainly from 2b 1 expands to a greater extent, compared to that on the dorsal-left side (mainly from 2b 2, Fig. 4t vs. vs.u u ). The second quartet (2d)The ectodermal progeny of 2d originally lie along the very posterior edge of the blastopore (Figs. 6a–b and and14), 14 ), but this is the only clone of second quartet cells that is eventually excluded from the blastopore lip and does not contribute to either the esophagus or the mouth (Figs. 6b–p and and15). 15 ). These cells are pushed away from the lip when clones derived from 3c and 3d, specifically 3c 2 and 3d 2, fuse along the ventral midline at approximately 97 hpf (Figs. 6j, ,10, 10,,11, 11, ,12, 12, and and14). 14 ). That behavior is described in greater detail below. 2d 1 and 2d 2 give rise to nearly bilaterally symmetrical clones of posterior ectoderm (Fig. 6l – m, ,q q – s ). Both of these cells give rise to much of the post-trochal ectoderm and both contribute also to the formation of the shell gland and the mantle (Figs. 6t – dd and and14). 14 ). There are two unlabeled voids inside the posterior clone of labeled 2d cells that represent the two “terminal cells” derived from 3c 2 and 3d 2, respectively (Figs. (Figs.6q 6q and 13b; see further discussion below). As cells derived from 3c 2 and 3d 2 extend posteriorly into these clones (together with cells derived from 3c 1 and 3d 1 ), they cleave them to form two “V” shaped arms, one each derived from 2d 1 and 2d 2, respectively (Fig. 6q – s ). These two arms each contain three cells that ultimately form bilateral, neuro-sensory structures located in the foot (Fig. 6v – dd; see description by [ 31 ]). 2d also gives rise to prominent neurons that extend from the post-trochal region to those neuro-sensory cells that become located in the tip of the foot, as well as to the apical organ in the head. A prominent pair of bilateral ganglia are located on the left and right sides of the post-trochal region from which these axons extend (Fig. 6bb, ,cc). cc ). The tip of the developing hindgut intestine is located directly under posterior ectoderm derived from 2d (Figs. 6 and 13a – j ). Often, there is a fluorescently brighter patch of labeled ectoderm directly over the terminal end of the hindgut that is derived from 2d 2 (Fig. 13b, ,d, d, ,f f – g ). As asymmetric rotation of the visceral mass takes place, this patch of ectoderm follows the posterior end of the digestive tract and moves up the right side of the developing veliger larva (Fig. 13a – c, ,h h – j ). The proctodeum or anus opens within this 2d 2 derived ectoderm later in development at approximately 12 days of development (Figs. 13h – j and and15 15 ). The third quartet (3a and 3b)All four of the third quartet micromeres generate cells located along the lip of the blastopore (Figs. 3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, ,13, 13, and and14). 14 ). Together, these contribute to most of the circumference of the blastopore. 3a and 3b give rise to bilaterally symmetrical clones that reside on the left and right sides of the embryo, respectively, which are situated closer to the future anterior pole (Figs. 7b – f and and8b 8b – e ). Their vegetal most progeny, derived from 3a 2 and 3b 2 are the ones that initially lie along the anterior-lateral rim of the blastopore (Fig. 14 ). These cells ultimately dive deep during gastrulation and form the ectomesoderm (Figs. 7h – o, ,8f, 8f, ,h h – k,,m, m, ,n, n, and are described in greater detail below, and Fig. 9 ). As this happens, the animal progeny derived from 3a 1 and 3b 1, in turn take their place along the rim of the blastopore lip/blastopore boundary and contribute to the development of the esophagus and the mouth (Figs. 7j, ,k k and and8l). 8l ). Cells arrayed in short straight bands extend to the left and right sides of the 3a 1 and 3b 1 clones away from the blastopore/mouth (Figs. 7h – p and and8g 8g – j, ,l). l ). These arms extend only as far as the lateral edges of the embryo. These clones contribute to the food groove and metatroch and post-trochal (post-oral) velar ectoderm in the vicinity of the mouth and the foot (Figs. 7o, ,p p and and8n, 8n, ,o o ). Formation and behavior of ectomesoderm (3a 2and 3b 2)The lineage analyses described above revealed that ectomesoderm arises from the 3a 2and 3b 2 micromeres. These cells initially divide twice to form a line of four cells located along the anterior-lateral edges of the blastopore, at the boundary with the blastopore lip (Figs. 9a – i, ,14, 14, 16a ). Ultimately, these cells undergo further proliferation to give rise to a larger number of mesenchymal cells (Figs. 7, ,8, 8, and and9j 9j – u ). As gastrulation takes place, these cells roll into the blastopore to occupy deeper positions (Fig. 9s – u; Additional files 6 and 7 ). As this begins to take place, the anterior blastopore narrows (Figs. 2 and and8f), 8f ), and these cells appear to loosen contacts with neighboring cells and become more rounded (Fig. 9t, ,u). u ). Eventually, they are covered by cells derived from their sister clones (3a 1 and 3b 1 ), which are part of the ectodermal lip of the blastopore (Figs. 9t, ,u u and and14). 14 ). The 3a 2 and 3b 2 progeny are internalized by a process of ingression and ultimately undergo epithelial-mesenchymal transition (EMT). They begin to migrate to remote locations within the embryo and larva beginning around 142 hpf (Fig. 9v–z; Additional file 8 ). Some of the progeny derived from the left 3a 2 and right 3b 2 micromeres cross the ventral midline during their migration (Figs. 7j, ,n n and and8i). 8i ). These cells form various fates, including velar muscles, muscles of the foot, as well as some fibers in the main retractor muscles, the latter being derived primarily from 4d (see [ 31 ]). The third quartet (3c and 3d)3c and 3d give rise to bilaterally symmetrical (right and left) clones located along the posterior lip of the blastopore (Figs. 10, ,11, 11, ,12, 12, and and14). 14 ). These cells contribute to the mouth, esophagus, foot, and post-trochal region (Fig. 15 ). The vegetal progeny, derived from 3c 2 and 3d 2, initially lie along the rim of the blastopore lip (Figs. 10d, 11d, and 12a, ,s). s ). These cells each give rise to four progeny that form a single line of cells along the lip that do not divide further (Figs. 12 and and14). 14 ). The medial ends of these two lines of cells are initially separated from one another by cells derived from 2d 1 and 2d 2 (Figs. 6, ,14 14 and and16). 16 ). Subsequently, 3c 2 and 3d 2 progeny move toward the ventral midline by a process of convergence and extension, and undergo intercalation, which is described in greater detail in the next section (Fig. 12 ). These cells all become multi-ciliated and form a group of cells that extends along the ventral midline, from the posterior esophagus and mouth, to the posterior end of the embryo (Fig. 12dd, ,ee ee ). The much larger group of cells derived from 3c 1and 3d 1contribute mainly to the left and right halves of the foot and to the statocysts (Figs. 10m–t, 11m, ,p p – x, and and15). 15 ). In addition, these cells give rise to thin bands that lie within the post-trochal ectoderm on the posterior surface of the right and left velar lobes (Figs. 10p – r, 11n – u, and 13k – o ). Hejnol et al. [ 31] indicated that 3c and 3d give rise to the left and right external larval kidneys, but Lyons et al. [ 34] showed that both the left and right external larval kidneys (absorptive cells) are derived from 4d. The posterior blastopore lip: closure by convergence and extension At flattened round stages, the posterior/lateral lip of the blastopore is made up of two lines of four cells each derived from the vegetal-most daughters of the 3c and 3d (i.e., 3c 2 and 3d 2; Fig. 12a, s ). Initially, derivatives of 2d 1 and 2d 2 cells lie between these 3c 2 and 3d 2 cells at the lip (Figs. 6j, 12v, x, ,z, z, and and14). 14 ). At approximately 97 hpf, 2d 1 and 2d 2 are pushed away from the posterior lip when the 3c 2 and 3d 2 progeny subsequently interdigitate by zippering along the ventral midline (Figs. 12a–u and and14; 14; Additional file 9 ). This zippering is accomplished by a novel form of convergence and extension. A consequence of this zippering process is that the posterior blastopore lip closes, narrowing the blastopore. Beginning at the time, these cells undergo zippering; they all become multi-ciliated (Fig. 12 12bb bb – mm; Additional file 10 ). Each of these four 3c 2 and 3d 2 progeny extend a long thin filopodial process along the edge of the blastopore lip that forms contacts at the posterior ventral midline (Fig. 12m–o ). Those cells subsequently converge along the ventral midline to form two columns of cells that undergo intercalation and extension. The four originally medial cells (3c 221, 3c 222, 3d 221, 3d 222) are displaced posteriorly and removed from the blastopore lip (Figs. 10f–j and 11e–j ). The four originally more lateral cells (3c 211, 3c 212, 3d 211, 3d 212) contribute to the mouth and esophagus (Figs. 10o–t, 11m–y, and and15), 15 ), where the two most lateral cells end up diving deep into the archenteron to contribute to the esophagus (3c 211, 3d 211; Figs. 10i–o, 11m, and 12s – ll ). Those next to them contribute to the posterior mouth (3c 212, 3d 212 ). The other cells form a line that extends along the ventral midline. Two of these lie just posterior to the opening of the mouth (3c 222, 3d 222 ). The two cells (3c 221, 3d 221) that were initially the most medial cells prior to zippering give rise to the bilateral right and left “anal” cells, respectively, which were described by Conklin [ 42 ]. Despite their name, these two cells do not contribute to the proctodeum and to avoid further confusion we have renamed them “terminal cells” (Fig. 15; [ 43 ]; see discussion ). As the 3c 2/3d 2-derived cells zipper, they displace 2d progeny further away from the blastopore lip and towards the posterior pole of the embryo. They extend into the clone of cells derived from 2d, so that after zippering has finished, two elongated V shaped left and right columns of cells extend from the main 2d clone (the right arm from 2d 2 and the left arm from 2d 1; Figs. 6q – s, 12z – aa, and and14). 14 ). The terminal cells initially lie within the clone of 2d ectoderm that sits over the terminal end of the hindgut (Figs. 10p – t and 11r – y ). Subsequently, the terminal cells are displaced further from the end of the hindgut (Fig. 13k – s ). Go to: Discussion Early epiboly: expansion of the micromere cap Gastrulation occurs by diverse mechanisms among spiralians [ 10 ]. Epiboly is common to many species with yolk-rich eggs, including Crepidula [ 10, 42 ]. Though there are gross morphological descriptions of this process, very few specifically focus on the behavior of individual cell lineages [ 16, 18 ]. Here, we traced the lineages of the second and third quartet micromeres to specific germ layers, and to openings of the digestive tract (Figs. 1, ,14, 14, and and15 15 ). In Crepidula, epiboly occurs as cells of the micromere cap proliferate and flatten to cover endodermal and mesodermal precursors (Figs. 1 and and2). 2 ). These events are similar to what was described for Helobdella [ 16] and for the flatworms Imogine mcgrathi and Maritigrella crozieri [ 44, 45 ]. However, a double layer of ectodermal cells does not form in Crepidula, as described in Maritigrella [ 44 ]. In Crepidula, cell divisions occur continuously during epiboly, throughout the epithelium, whereas in Helobdella, mitoses in the cap are largely restricted to early stages of epiboly, and cell division is rarely observed at the leading edge of the cap [ 16 ]. To cover the large, yolky macromeres, the micromere cap’s marginal circumference must first increase to reach the equator and then decrease as the cap narrows around the vegetal hemisphere of the embryo. This latter step is accomplished in Helobdella, in part, by virtue of that fact that cells at the leading edge become wedge shaped, with their narrow edges at the lip. This wedging behavior was not pronounced in Crepidula; however, we noticed extensive cell shape changes at the leading edge (Fig. 2 ). These changes are discussed further below, for each of the second and third quartet micromeres, which make up the leading edge of the epithelial cap. Origin and behavior of the ectomesoderm (progeny of 3a 2and 3b 2)Spiralians typically have two sources of mesoderm. The first is endo mesoderm, derived from the 4d micromere, and gives rise to mesodermal derivatives such as adult muscle, heart, and excretory structures [ 34, 46 ]. Spiralian endomesoderm appears to be highly conserved with endomesoderm in other metazoans, both in terms of cell fates [ 34, 46] and gene expression [ 47, 19, 23 ]. The second is ecto mesoderm, which arises from various second and third quartet cells, depending on the species examined [ 10, 48 ]. Ectomesoderm gives rise to scattered mesenchyme, which can contribute to larval tissues such as the velar muscles in Crepidula [ 10, 31, 48, 49 ]. Ectomesoderm is likely a spiralian innovation, and the behavior and profile of genes expressed in these cells are not well understood [ 10, 50, 51 ]. An earlier study in Crepidula followed the contributions of embryonic cells later into larval development and reported that ectomesoderm arises from 3a, 3b, and 2c [ 31 ]. The origin of ectomesoderm from 3a and 3b is considered to be a plesiomorphic character among spiralians [ 10, 31 ]. In the present study, we observed no evidence of ectomesoderm arising from 2c (though this may arise at later stages of development). We found that ectomesoderm arises more specifically from the 3a 2 and 3b 2 cells (Figs. 7 and and8 8 ). The mechanisms of ectomesoderm internalization have not been investigated in detail, but internalization is generally assumed to occur by an epithelial to mesenchymal transition (EMT) [ 10 ]. We show that clones of cells derived from 3a 2 and 3b 2 occupy the anterior-lateral sides of the blastopore by ~94 hpf when the lip has just passed the equator of the embryo (Table 1; Figs. 9 and and14). 14 ). Initially, these cells are rather large and flat, forming lines of stretched cells along the anterior-lateral rim of the blastopore. Subsequently, these cells round up and proliferate (Fig. 9 ). Their progeny remain well rounded (which may indicate that they have weaker adhesive properties) while they collectively sink into the archenteron (Figs. 7, ,8, 8, and and9). 9 ). As this occurs, these cells are covered by trailing cells derived from 3a 1 and 3b 1. Despite using various lineage tracers and fluorescently tagged biosensors for the actin cytoskeleton (utrophin-GFP), we did not observe any obvious signs of dynamic cell membrane protrusions (e.g., filopodia or lamellipodia), or evidence of apical constriction in these cells during the initial phase of their entering the archenteron. Thus, the early behavior of these cells is distinct when compared to classic forms of EMT, such as in sea urchin primary mesenchyme ingression, where ingressing cells exit the cell cycle, extend filopodia, and slip out of the epithelium [ 52 ]. Only after they become covered by the surface ectoderm and move into the archenteron do these ectomesodermal cells extend filopodia and disperse, crawling to distant locations within the embryo (Fig. 9; Additional file 8 ). Origin and formation of the mouth (second and third quartet)As ectomesoderm leaves the leading edge of the micromere cap, its circumference becomes reduced. This removal of cells may help drive constriction of the blastopore lip along its anterior-lateral edges, as the blastopore takes on a narrowed, slit-like appearance (Fig. 2 ). Likewise, other cells, derived from 2a, 2c and 3a–3d, also extend into the archenteron to form tissues of the foregut/esophagus, and this could also contribute to narrowing of the blastopore. Despite Conklin’s [ 42] statement, the blastopore does not completely close in Crepidula, and gives rise to the mouth in a true protostome fashion (Fig. 14 ), just as was recently reported for Ilyanassa [ 18 ]. Previous descriptions by Conklin [ 42] and Hejnol et al. [ 31] reported that the progeny of mainly the second quartet form the mouth in Crepidula, while third quartet progeny make the ectodermal esophagus (or foregut). By tracing the exact locations of these cells throughout gastrulation, we found that contributions to the mouth and esophagus are more complicated. The mouth is derived from 2a 2, 2b 2, 2c 1, 2c 2, 3a 1, 3b 1, 3c 1, 3c 2, 3d 1, and 3d 2, and all those except 2a 2 and 2b 2 also contribute to deeper tissues of the esophagus (Figs. 3, ,4, 4,,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, and and15). 15 ). These contributions are similar to those noted for Ilyanassa [ 18 ], including the small contribution of the 2b lineage (2b 2) to the anterior-most part of the mouth. Interestingly, the relative contribution of second versus third quartet lineages to the mouth and esophagus appears to vary across species (see discussions in [ 53] and [ 18 ]). It could be that differential proliferation and cell re-arrangements during blastopore narrowing, along with different contributions of these cells to ectomesoderm, accounts for species-specific variation. Convergence and extension of the posterior blastopore lip: “zippering” of 3c 2 and 3d 2 progeny By the time the blastopore lip has passed the equator, the posterior half of the blastopore lip is occupied by four cells derived from 3d 2 on the left and four cells from 3c 2 on the right (Figs. 1,,12, 12, ,14, 14, ,16). 16 ). Between them, at the very posterior-most edge of the lip, lie two cells derived from 2d 1 and 2d 2. Beginning at ~94 hpf, these two cells are excluded from the blastopore lip by convergence and extension that involves intercalation of some of the 3c 2 and 3d 2 descendants. During this process, these cells extend thin processes that make contact with cells from the opposite sides. This convergence begins with the most medial, posterior cells in each clone (3c 221, 3d 221 ), followed by more lateral, anterior cells, which is reminiscent of a closing zipper. As these cells converge, they form a pair of columns along the anterior-posterior axis that undergo intercalation to form a more extended column of ciliated cells (Fig. 12dd, ,ee ee ). This study presents the first description of blastopore lip morphogenesis using clonal analysis and live imaging. Closure of the posterior blastopore has been described in other species (e.g., Platynereis [ 23 ], Hydroides, [ 17 ], Patella, [ 43 ]), but the specific cell behaviors involved were not investigated. The behavior exhibited by Crepidula likely takes place in other spiralians. Although Chan and Lambert [ 18] do not specifically remark on this phenomenon, their images of the 3c and 3d clones show that Ilyanassa likely develops in a similar fashion (their Fig. 4j, n ). Among annelids, Woltereck’s [ 54] drawings of Polygordius, reveal a similar posterior-ventral “zig-zag” seam comprised of two columns of left and right cells, which might reflect a similar zippering behavior [ 7, 12, 54 ]. The process observed in Crepidula could also account for the arrangement of cells observed in the study of Lartillot et al. [ 43 ], in the gastropod Patella (see their Fig. 5 ). Those authors speculate that cells posterior to the blastopore elongate along the ventral midline by directed stem cell like divisions, but that was based solely on gene expression data and not on intracellular lineage tracing; it is possible that the elongation is instead the result of convergence and extension along with cell intercalation. Convergent extension was recently reported in the annelid Platynereis [ 55 ]; however, that process is different, as it occurs within two separate populations of neuroectodermal precursors that lie to the sides of the ventral midline after blastopore closure has taken place. Lineage tracing in each of these species would address how similar their gastrulation processes are to that found in Crepidula. Ciliary bands: the food groove and the metatroch (second and third quartet)Hejnol et al. [ 31] reported that the metatroch, a ciliated, reverse-current (downstream) feeding band, is derived from 2a and 2c, while the ciliated food groove, lying between the metatroch and the prototroch (derived from the first quartet micromeres), is derived from 2b (Fig. 4 ). Here, we extend those results by showing that the food groove is derived from both 2b 1 and 2b 2, in addition to 3a 1 and 3b 1, and the metatroch is derived from 2a 2 and 2c 2, as well as 3a 1 and 3b 1. The 3c 1 and 3d 1 clones also extend long thin bands of cells, but those are located on the posterior surface of the velum, behind the metatroch. The differences between our studies may be related to the fact that Hejnol et al. [ 31] examined fixed embryos, and we analyzed live material, which is much better for making fine assessments of cell lineage fates. Gharbiah et al. [ 56] reported in Ilyanassa that the metatroch arises from 3a–3d and 2a–2c, and the food groove is from 2a–2c, as well as 3a–3b. These findings continue to support the argument that the homologization of these ciliated bands across large evolutionary distances is problematic [ 57 ]. The neurotroch (3c 222, 3c 222)Following the zippering of the posterior blastopore lip, the daughter cells from 3d 2and 3c 2each contribute to four sets of ciliated cells present in the posterior ventral ectoderm (Fig. 12 ). These include two deeper cells in the esophagus (3c 211, 3d 211 ), two in the mouth (3c 212, 3d 212 ), two cells we believe could be analogous to a neurotroch (3c 222, 3d 222 ), and more posteriorly, two “terminal cells” that could be analogous to a telotroch (3c 221, 3d 221 ). These cells all become ciliated during posterior blastopore closure (Fig. 12bb – mm ). In some larvae of other spiralians, the neurotroch (also sometimes called the gastrotroch, but not to be confused with the ciliated bands on the segments of polychaetes; see [ 58 ]) represents a double row of multi-ciliated cells that runs along the ventral midline, posterior to the mouth and extends towards the anus [ 59 ]. The neurotroch has been argued to be a plesiomorphic feature of spiralian larvae [ 60 – 62 ]. Cilia of the neurotroch beat towards the anus, but the exact function of the neurotroch is uncertain. This structure, which is present in some annelids and entoprocts, is apparently not found in platyhelminthes, nemerteans, rotifers, or molluscs [ 60, 62 ]. The neurotroch typically comes from the 2d lineage [ 29 ]. For example, in Capitella, the neurotroch is made up primarily of 2d cells, with 3c and 3d also contributing a small number of anterior cells [ 53 ]. In Ilyanassa, there are a few ciliated cells in the foot [ 56] derived from 3c and 3d [ 18 ]. We argue that the 3c 222 and 3d 222 cells of Crepidula could be analogous, or even homologous, to the neurotroch in other spiralians. The telotroch (3c 221and 3d 221)The telotroch (sometimes referred to as paratroch) represents a posterior ciliated band that encircles the anus and is believed to have a function in locomotion [ 63 ]. Telotrochs have been found in many annelids (including echiurans and sipunculids) and some molluscs, including the gastropod Patella [ 53, 64 – 66 ]. Its presence has also been reported for aplacophorans (e.g., Neominiomorpha and Chaetodermorpha ), and given their basal position in the Mollusca, this structure is regarded as a plesiomorphic condition for that phylum [ 60, 67 ]. A telotroch has also been reported for the pilidium larva of one nemertean [ 68, 69 ], though this is likely a derived structure. Nielsen [ 60] argues that the telotroch is a feature of the ancestral trochophore larva, though Strathmann [ 63] suggests this structure could have evolved on multiple occasions, and Rouse [ 67] argues that only the prototroch is ancestral for the Trochozoa. The telotroch is said to be derived from 2d in the annelids Arenicola [ 70] and Amphitrite ( [ 29, 71 ]). The telotroch in the polychaete annelid Capitella is also derived from 2d [ 53, 65 ]. In the gastropod Patella, the telotroch is mainly derived from 2d, but includes two distinctive anterior ciliated cells derived from 3c and 3d [ 64 ]. We argue that the two posterior ciliated cells in Crepidula (3c 221 and 3d 221) are homologous to those two telotroch cells. These represent the posterior-most cells in the Crepidula embryo following posterior blastopore lip closure (Fig. 12s–u ). They are surrounded by ectoderm derived from 2d, and they are the only ciliated cells in this region (Figs. 6q, x and 12ff, ,gg). gg ). These cells represent what Conklin [ 42] and others referred to as “anal cells,” as they assumed that they contributed to the proctodeum. We show clearly that these cells do not make the anus, which arises instead from the 2d lineage (2d 2, see below). Thus, we deemed it necessary to re-name these cells, and propose calling them “terminal cells”; the term used for what we assume to be the homologous cells in Patella [ 43 ]. Lartillot et al. [ 43] stated that terminal cells arise from the 3c 11 and 3d 11, and that these cells give rise to the anus, but there is no published lineage data to support those claims. Origin and formation of the anus (2d 2)There are various reports regarding the origins of the ectodermal anus (proctodeum) in spiralians [ 10, 53 ]. In the classical literature, for instance, Treadwell [ 72] argued that cells derived from 3c give rise to part of the proctodeum in Podarke, but Nielsen [ 29] suggests that this is not well demonstrated. The anus was said to be derived from 2d in the annelids Arenicola [ 70] and Amphitrite (Nielsen [ 29 ]). More recently, intracellular lineage tracing in Capitella [ 53] showed that the ectodermal anus is derived from 4d, which appears to be a unique situation. As mentioned above, earlier investigators referred to ciliated “anal cells”, which were thought to give rise to the anus (e.g., [ 42, 73 ]). We show in Crepidula that these terminal cells (derived from 3c 221 and 3d 221) are located near the end of the hindgut early during development, but they become displaced from this location at later stages (Fig. 13k–s ). Instead, our current study demonstrates that the anus is derived from the 2d 2 clone, which forms ectoderm lying directly over the termination of the hindgut (Fig. 13a–j ). In Capitella, the 2d clone also surrounds the 4d-derived anus, and the 3c and 3d micromeres contribute cells to this area as well, but are subsurface, as 3c and 3d progeny are ectomesodermal in this species [ 53 ]. In a previous study [ 34 ], we observed that the anus did not form when specific progeny of 4d were ablated (e.g., 3m L/R), which contributes largely to the formation of the terminal endoderm of the hindgut. These data suggested that inductive interactions may be required to induce the formation of the proctodeum. It is possible, however, that we did not follow those larvae long enough to fully determine if the anus could form or not. Its development could have also been delayed in those experimental cases. In the course of this study, we found that the opening of the anus does not appear until 12 days after fertilization. On the other hand, the location of the anus may indeed require inductive interactions from the hindgut, as suggested by those earlier experiments. When performing the lineage analyses here, we noticed that the hindgut becomes distended or swollen before the anus opens (Fig. 13j ). At that point, the intestine collapses down to a narrow tube and cylindrical waist products begin to be expelled. In some of the injected cases, there was no lineage tracer observed, which resulted from the accidental death of those injected 2d cells (data not shown). In those same cases, the anus does not appear to open and the hindgut remains swollen, even though ectoderm covers the terminal end of the intestine. These findings suggest that only the progeny of 2d may form the anus, and that these may be the only cells competent to respond to inductive interactions from the terminal hindgut endoderm. It is possible that differences in the spatial relationships and inductive interactions between the hindgut (endodermal) terminus and the overlying ectoderm could account for species-specific variations in those cells that have been reported to give rise to the anus. Differences between Crepidula blastopore morphogenesis and amphistomy The relationship between the blastopore and the mouth and anus is under debate [ 2, 5, 7, 8, 10, 22, 23 ]. The fact that there is variation in the site and behavior of the blastopore takes on particular evolutionary significance because the blastopore is developmentally related both to the blind gut of bilaterian out groups, like cnidarians, and to the through-gut of bilaterians. Thus, it is reasoned that diverse bilaterian body-plans are related to, or even dependent on, changes to the site or behavior of the blastopore. How did these changes come about? According to one set of hypotheses, the bilaterian ancestor exhibited amphistomy, where a slit-like blastopore gave rise to both mouth and anus [ 3, 5 ]. According to this theory, protostomy and deuterostomy evolved from amphistomy as openings were retained at only the anterior or posterior end of the blastopore. An alternative scenario argues that deuterostomy is ancestral among bilaterians, including ecdysozoans and spiralians/lophotrochozoans, and thus protostomy arose independently on multiple occasions as a modification of deuterostomy [ 6 ]. Thinking even more broadly, it has even been called into question if there are technically any prostostomes among the bilaterians, because the blastopore forms at the posterior pole in the Spiralia, but the mouth forms in the anterior ventral ectoderm from cells that were born near the animal pole [ 2, 13 ]. The detailed cell lineage studies that are necessary to distinguish between these hypotheses are often lacking within the spiralian/lophotrochozoan branch. Very few examples of amphistomy, or deuterostomy, are reported among species with spiral cleavage, and no lineage tracing study has definitively documented either phenomenon [ 7, 10 ]. Despite the lack of strong evidence, the gastrulation behaviors of several species have been called upon to support the existence of amphistomy, or the remnants of an amphistomous ancestor. For example, some point to Woltereck’s description of a slit-like blastopore in the annelid Polygordius as an extant example of amphistomy [ 5, 8, 54 ]. Yet, others disagree with this interpretation, pointing out that Woltereck himself stated, and illustrated, that the posterior portion of the blastopore closes, while the anus arises from 2d-derived cells in a more posterior location [ 7, 12 ], which is similar to what we observed in Crepidula. The behavior of extant species has been taken as evidence of a transition from amphistomy to protostomy. The development of Patella [ 43 ], Hydroides [ 17 ], and Platynereis [ 23] has been interpreted in this way because the blastopore is said to seal up along the posterior ventral midline. The zippering phenomenon that we observed in Crepidula might be homologous to the gastrulation processes in these other spiralian species. However, no lineage tracing has correlated the position of clones around the blastopore with the formation of the mouth or anus in these species. By emphasizing the behavior of the blastopore lip cells, and defining them as those cells that surround the endoderm/mesoderm in Crepidula (Fig. 16 ), we hope to establish a basis of comparison with other species. Central to the definition of amphistomy are the notions that in the amphistomous ancestor: 1) the lateral edges of the blastopore fused, which 2) left persistent anterior and posterior holes, that 3) resulted in the simultaneous formation of the openings that became those of the mouth and anus, respectively. However, the behavior of the Crepidula blastopore deviates from these definitions in several respects. First, zippering of the posterior blastopore lip occurs in a posterior to anterior direction, rather than initiating at the lateral edges of the lip. Second, only one hole persists after gastrulation and this becomes the mouth. Third, it is not just the anterior portion of the blastopore lip that gives rise to the mouth, but clones from anterior, lateral, and posterior positions (Fig. 16 ). Fourth, the mouth also forms from anterior, lateral, and posterior cells that were never part of the blastopore lip (Figs. 14, ,15, 15, and and16). 16 ). Fifth, the anus arises as a separate hole from the blastopore, days after gastrulation has finished. Some might view the behavior of cells at the posterior blastopore lip in Crepidula as an example of the proposed transition from amphistomy to protostomy (see [ 3, 5 ]), At the beginning of gastrulation (~90 hpf, Fig. 1d; Fig. 14, second row; Fig. 16a ), each of second and third quartet micromere lineages contribute progeny to the lip, including cells that give rise to the mouth (2a–2c, 3a–3d) and much later, to the anus (2d). In this context, one could claim that cells of the early blastopore lip include progenitors that form both the mouth and the anus. We note, however, that the progenitor cells that give rise to the anus are part of the blastopore lip for only a short duration, before being quickly excluded by the zippering of the 3c 2 and 3d 2 clones. Furthermore, during the time the 2d clone is part of the blastopore lip, the anus has not yet formed. Finally, we note that we have chosen to define the blastopore lip at a very early time in development (Fig. 16a ), by virtue of the fact that the ectodermal micromere cap internalizes the macromeres from the very beginning of epiboly. If however, we took a more conservative approach and said that the blastopore lip does not form until later, when an obvious depression/archenteron forms (Fig. 16b, c ), then the 2d clone would not be present at the blastopore lip. The definition of when the blastopore/blastopore lip forms is somewhat subjective and might vary species to species. These semantic debates reflect how difficult it can be to make direct comparisons when talking about distantly related animals whose gastrulation processes are diverse; by making an explicit definition of the blastopore lip, we hope to make future comparisons with other animals more straightforward. While we cannot exclude the possibility that Crepidula blastopore morphogenesis has been modified from an ancestral amphistomy condition, we note that no extant species has been shown to exhibit amphistomy, and classic examples of amphistomy have been called into question by many authorities [ 7, 11, 12 ]. Therefore, we argue that it is unlikely that protostomy is a modification of amphistomy. If deuterostomy is ancestral to the bilaterians, as has been recently proposed (based on its widespread existence in extant deuterostomes and ecdysozoans [ 6, 11 ]), it will be of interest to understand the morphogenetic changes to cells around the blastopore that permitted such a transition. We propose that it will be more useful to focus on homologizing cells at the blastopore lip (which can be lineage-traced, or assayed for expression of regulatory genes), than to focus on the blastopore hole itself. Go to: Conclusions A morphogenetic perspective on the evolution of spiralian gastrulation Very little is understood about the underlying morphogenetic processes that occur during spiralian development. Focusing on behaviors of specific lineages will be very informative for comparative studies. Examining the cells that make the blastopore in different species is just one example. We mention a few additional examples below. We found that the 3q 2cells exhibit highly dynamic behaviors in Crepidula. Cells derived from 3a 2 and 3b 2 undergo EMT during formation of the ectomesoderm, and the 3c 2 and 3d 2 cells undergo convergence and extension to close the posterior blastopore lip. These cells display other interesting differences: the 3a 2 /3b 2 cells divide multiple times (giving rise to dozens of cells each), never become ciliated, and only form filopodia after they have become mesenchymal. Conversely, the 3c 2 /3d 2 cells divide only twice (giving rise to just four cells each), become multi-ciliated, and form filopodia while still remaining in the ectoderm. How these third quartet cells acquire their unique identities will be an interesting area of future research. In Ilyanassa, inheritance of m RNA can distinguish different tiers of micromeres along the animal vegetal axis [ 74] while differential stability of m RNAs along the anterior-posterior/dorsal ventral axis can then distinguish different quadrants [ 50 ]. For example, the Tis11 transcript is initially inherited by all 3q micromeres, but is retained in only the 3a and 3b cells, which form ectomesoderm [ 18, 50 ]. In other species, like Platynereis and Capitella, the 3c and 3d cells contribute to ectomesoderm, and it would be interesting to compare cellular and molecular events within these different tiers and quartets of micromeres to understand the basis of this inter-species variation. Another fruitful area of research would be comparing species that gastrulate by epiboly, emboly, and invagination [ 10 ]. For example, in Crepidula, the blastopore lip has to narrow considerably to cover the large endodermal macromeres; the zippering behavior we observed in the posterior blastopore lip might be necessary to cover those cells. During invagination, in contrast, the endodermal cells are smaller, and the ectodermal cells near them might behave differently. Furthermore, it would be interesting to study how similar the movement of cells towards the ventral midline in Patella, Hydroides, and Platynereis are to that in Crepidula. In Capitella, the blastopore has been described to close completely [ 19 ], which might be accomplished by a more extensive zippering behavior, or a completely distinct mechanism. Studying the details of cell lineages and their behaviors will address how such variation arose. Finally, spiralians are one of the only groups of metazoans where homology of body-plans can be compared at the levels of gene expression and cell lineage. Comparison of gene expression patterns in the posterior and anterior blastopore lip has been used in arguments about amphistomy [ 23, 43, 75 ], but in the absence of detailed lineage tracing during gastrulation stages. It has been proposed that the differences in gene expression for endomesodermal markers might be a reflection of different life history strategies [ 17 ], which also correlate with different modes of gastrulation [ 10 ]. To test this interesting hypothesis, it will be necessary to have both gene expression and fate map data for multiple species [ 76 ]. Our goal here is to provide a framework for comparative studies of morphogenesis, in the hope that Crepidula will provide a useful point of reference for similar studies in other species. Go to: Acknowledgements The authors thank the community of the Marine Biological Laboratory and especially Drs. Richard Behringer and Alejandro Sanchez Alvarado. DCL thanks DR Mc Clay for his support. We also thank Drs. Ray Keller, Mark Martindale, Elaine Seaver, Marc Servetnick, and Jose Martín-Durán for helpful discussions, as well as three anonymous reviewers for comments that improved the manuscript. This material is based upon work supported by the National Science Foundation under Grant No. 1121268 to JQH (JJH). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. Go to: Abbreviations Hpf hours post-fertilization Q macromere quartetq micromere quartet EMT epithelial-to-mesenchymal transition Additional files Additional file 1: (3.8M, mov)Movie 1.mov (Figure S1). Time lapse light sheet confocal images of an embryo expressing the microtubule-cytoskeleton bio-sensor EMTB-GFP ( green) and an RFP-membrane biosensor ( red ). Corresponds to Figure 1s. Additional file 2: (719K, mov)Movie 2.mov (Figure 2f). Time-lapse movie of embryos expressing UTPH-GFP during early epiboly. Corresponds to Figure 2f. Additional file 3 (856K, mov)Movie 3.mov (Figure 2g). Time-lapse movie of embryos expressing UTPH-GFP during later epiboly. Corresponds to Figure 2g. Additional file 4: (829K, mov)Movie 4.mov (Figure 2h). Time-lapse movie of embryos expressing UTPH-GFP during elongation. Corresponds to Figure 2h. Additional file 5: (566K, mov)Movie 5.mov (Figure 2i). Time-lapse movie of embryos expressing UTPH-GFP during mouth formation. Corresponds to Figure 2i. Additional file 6: (992K, mov)Movie 6.mov (Figure 9a). Time-lapse movie of an embryo injected with utrophin-GFP (UTPH) to mark cell outlines ( green ), and histone H2B-RFP (H2B) to mark nuclei ( yellow ). Ventral view. Corresponds to Figure 9a–i. Additional file 7: (1.6M, mov)Movie 7.mov (Figure 9j). Time-lapse movie of an embryo injected with ensconsin-GFP (EMTB) to mark microtubules ( green ), and histone-RFP (H2B) to mark nuclei ( yellow ). Ventral view. Corresponds to Figure 9j–u. Additional file 8: (1.2M, mov)Movie 8.mov (Figure 9v). Spinning disk confocal time-lapse of an embryo expressing utrophin-GFP (UTPH) globally ( green ), and in which the 3b micromere was labeled with di I ( red ). Ventral view. Corresponds to Figure 9v–z. Additional file 9: (3.6M, mov)Movie 9.mov (Figure 12b). Time-lapse movie of an embryo undergoing convergence and extension to zipper the posterior blastopore closed. The 3c cell was injected with dextran ( green) and the 3d cell was injected with di I ( red ). Corresponds to Figure 12b–l. Additional file 10: (111K, mov)Movie 10.mov (Figure 12w). Confocal time-lapse movie of 3c 2cells injected with di I, showing the beating of cilia. Corresponds to Figure 12w. Additional file 11: (11M, tiff)Figure S1. Early epiboly and position of clones at the blastopore lip. a–h Cartoons of early embryo with second and third quartet micromeres colored, as indicated in key to the right. a–c Animal pole views; d is a ventral/vegetal view; e–h are lateral views. Black and white cartoons are modified from Conklin’s drawings [ 42 ]. i–r Images of embryos during late cleavage and early epiboly stages labeled with the actin cytoskeleton marker UTPH-GFP ( white) and histone H2B-RFP (red); in some panels, the 4d clone is labeled with di I (red). AV animal pole view, VV ventral/vegetal pole view, LV lateral view. The 4d clone can often be identified without direct labeling because the UTPH-GFP is preferentially expressed or stabilized in this clone (e.g. as in l, m, q, r ). Scale bar equals 50 μm. s–w Time lapse light sheet confocal images of an embryo expressing the microtubule-cytoskeleton bio-sensor EMTB-GFP and an RFP-membrane biosensor (MEM-RFP). Lateral view. Many cells are seen to divide over the course of the time-lapse ( arrow mitotic spindle), but the micromere cap does not make a significant advance towards the vegetal pole during this period. See also Additional file 1, which corresponds to panels s–w. Additional file 12: (18M, tiff)Figure S2. Narrowing of the blastopore during later epiboly, and formation of the mouth/stomodeum. a–e Confocal images of living embryos expressing UTPH-GFP to mark the actin cytoskeleton, and histone H2B-RFP to mark the nuclei. Ventral views are shown during mid epiboly ( a ), late epiboly ( b ), elongation ( c ), and mouth formation ( d–e ). f–i Time-lapse movies of embryos expressing UTPH-GFP during epiboly and mouth formation. VV ventral view. Scale bar equals 50 μm. See also Additional files 2, 3, 4, and 5, which correspond to panels f, g, h, and i. Additional file 13: (12M, tiff)Figure S3. Fates of micromere 2a, and its subclones, during gastrulation and organogenesis. Images of live embryos with dextran- and di I-labeled 2a, or 2a subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated. Anterior is up in all cases. a Ventral view during early epiboly. Corresponding ventral-view images are shown in b-c, d-e, f-g during late epiboly with different combinations of fluorescence and/or DIC layers shown. h Shows a dorsal view of the same embryo shown in f-g. i, j Ventral views of older elongating embryos. k, l Corresponding right lateral views of an older embryo undergoing organogenesis. m Left lateral view of an older embryo undergoing organogenesis. n, o Corresponding left lateral view of an older embryo undergoing organogenesis. bp blastopore, ft foot, hg hindgut rudiment, mt metatroch, pgc primordial germ cell, rtc right terminal cell, sg shell gland, st stomodeum/mouth. Scale bar equals 50 μm. Additional file 14: (19M, tiff)Figure S4. Fates of micromere 2b, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 2b, or 2b subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated. Anterior is up in all cases. a Ventral view during an early stage of epiboly. b Ventral view during a later stage of epiboly. Corresponding ventral views are shown in c-d, e-f, g-h, i-j during epiboly with different combinations of fluorescence and/or DIC layers shown. Corresponding dorsal images are shown in k-l, m-n during epiboly. o–q Ventral views of older, elongated embryos. r Oblique left-lateral view of the ventral surface of an older embryo. Corresponding left-lateral images are depicted in s-t and x-y of older embryos undergoing organogenesis. u Right lateral view of an older embryo undergoing organogenesis. v, w Corresponding oblique left-lateral views of the ventral surface of an older embryo undergoing organogenesis. fg food groove, nc neural cells. Other labels are the same as those used in Fig. 3. Scale bar equals 50 μm Additional file 15: (15M, tiff)Figure S5. Fates of micromere 2c, and its subclones, during gastrulation and organogenesis. Images of live embryos with dextran and di I labeled 2c, or 2c subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated. Anterior is up in all cases. a, b Corresponding ventral and dorsal views of an embryo near the end of gastrulation with different combinations of fluorescence and/or DIC layers shown. c, d Corresponding ventral views of an embryo near the end of gastrulation. e, f Corresponding ventral views of a slightly older embryo at the end of gastrulation. g, h Corresponding ventral views of an older elongating embryo. i Dorsal view of an elongating embryo. j Ventral surface view of an embryo at the onset of organogenesis. k, l Corresponding right lateral views of an embryo at the onset of organogenesis. m, n Corresponding right lateral views of an older embryo during organogenesis. o, p Corresponding oblique dorsal view of an embryo during organogenesis. Corresponding right-lateral views of embryos undergoing organogenesis are shown in q-r, s-t. tc terminal cells. Other labels are the same as those used in Fig. 3. Scale bar equals 50 μm. Additional file 16: (18M, tiff)Figure S6. Fates of micromere 2d, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 2d, or 2d subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated. Animal pole is up in a, anterior is up in b–dd. a Dorso-lateral view of an early epiboly-stage embryo. Corresponding ventral views of embryos during epiboly are shown in b-c, d-e, f-g with different combinations of fluorescence and/or DIC layers shown. h, i Corresponding dorsal views of same embryo shown in f, g. Corresponding ventral view images of successively older embryos undergoing epiboly are shown in j-k, l-m. n, o Shows corresponding dorsal views of an embryo at the same stage as that shown in l, m. p Ventral surface view of an elongated embryo. q Ventral view of embryo undergoing elongation. Note unlabeled voids where the two terminal cells (tc) from 3c 221 and 3d 221 reside. r, s Corresponding ventral views of embryo undergoing elongation. t, u Right-lateral views of older embryo at the onset of organogenesis. v, w Corresponding left-lateral views of embryo at the onset of organogenesis. x, y Ventral views of embryo undergoing elongation. Unlabeled voids occupied by the two terminal cells ( tc) are also indicated in x. Corresponding left-lateral ( z, aa) and right-lateral/oblique ( bb, cc) views of older embryos during organogenesis. dd Shows a ventral view of an embryo during organogenesis. pb polar body, ns neurosensory cell. Other labels are the same as those used in Figs. 3 and and4. 4. Scale bar equals 50 μm. Additional file 17: (12M, tiff)Figure S7. Fates of micromere 3a, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3a, or 3a subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated. Animal pole is up in a. Anterior is up in b–o. a Dorso-lateral view of an early epiboly-stage embryo. b Ventral (vegetal) view of early epiboly-stage embryo. c-d, e-f Show corresponding ventral views of early and mid epiboly-staged embryos, respectively, with different combinations of fluorescence and/or DIC layers shown. g, h Corresponding ventral views of later stage embryos undergoing epiboly. i Ventral view of an older, elongating embryo. j, k Ventral views of two embryos just prior to the onset of organogenesis. Note that for the original stack of confocal images shown as a projection in j, the 3a 1 and 3a 2 clones are spatially separated in the Z axis, making it possible to pseudocolor them separately, as labeled. Corresponding ventral views of embryo just prior to the onset of organogenesis are shown in l, m, n, o Left-lateral view of an embryo during organogenesis. cb ciliary band, ms mesenchyme. Other labels are the same as those used in Figs. 3 and and6. 6. Scale bar equals 50μm. Additional file 18: (12M, tiff)Figure S8. Fates of micromere 3b, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3b, or 3b subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated. Animal pole is up in a. Anterior is up in b–o. a Lateral-dorsal view of an early epiboly-stage embryo. b-c, d-e show corresponding ventral (vegetal) views of early epiboly-staged embryos with different combinations of fluorescence and/or DIC layers shown. f Ventral view of embryo during later epiboly. g, h Show ventral views of two stages of mesenchyme migration. i Ventral view showing numerous mesenchyme cells. j, k Corresponding right-lateral views of embryos during organogenesis. l, m Ventral surface views. n, o Corresponding right-lateral views of older embryos during organogenesis. Labels are the same as those used in Figs. 3, ,6, 6, and and7. 7. Scale bar equals 50 μm. Additional file 19: (18M, tiff)Figure S9. Behavior of ectomesoderm (3a 2, 3b 2). a–i Time-lapse movie of an embryo injected with utrophin-GFP (UTPH) to mark cell outlines, and histone H2B-RFP (H2B) to mark nuclei, where indicated. Ventral view. bp blastopore. Several unidentified (x) daughter cells of 3a 2, 3b 2 are marked, in colors, to show the orientation of cell division and position of ectomesodermal precursor cells during the narrowing of the anterior blastopore lip. Scale bar in f equals 50 μm; scale bar in i equals 25 μm. j–u Frames from a timelapse movie of an embryo injected with ensconsin-GFP (EMTB) to mark microtubules, and histone-RFP (H2B) to mark nuclei. Ventral view. Dashed white lines outline the 3b 2 clone. Scale bar in u equals 30 μm. v–z Spinning disk confocal frames from a time-lapse of an embryo expressing utrophin-GFP (UTPH) globally, and in which the 3b micromere was labeled with di I (red). Ventral view. Scale bar in z equals 50 μm. See also Additional files 6, 7, and 8. Additional file 20: (15M, tiff)Figure S10. Fates of micromere 3c, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3c, or 3c subclones, as indicated. Animal pole is up in a and b. Anterior is up in c–t. a, b Dorso-lateral views of early epiboly-stage embryos. c, d Ventral views of early epiboly-stage embryos. Corresponding ventral views of late epiboly-stage embryos are shown in e-f, g-h, i-j at successive stages of development with different combinations of fluorescence and/or DIC layers shown. k, l Corresponding ventral and posterior views of an elongating embryo. m, n Ventral views of embryos during elongation. Corresponding right-lateral views of embryos during organogenesis o-p, s-t. Note green background fluorescence is higher in s, t. (Q-R) Corresponding oblique, ventro-lateral views of an embryo during organogenesis. nt neurotroch, rtc right terminal cell, pvb posterior velar band. All other labels are the same as those used in Figs. 3 and and6. 6. Scale bar equals 50 μm. Additional file 21: (19M, tiff)Figure S11. Fates of micromere 3d, and its subclones, during gastrulation and organogenesis. Images of live embryos, with dextran and di I-labeled 4d, 3d, or 3d subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for the actin-binding domain of utrophin-GFP (UTPH) and histone H2B-RFP to visualize nuclei or cell outlines, respectively, where indicated. Animal pole is up in a and b. Anterior is up in c–y. a, b Dorso-lateral views of early epiboly-stage embryos. c, d Ventral views of early epiboly stage embryos. e–j Ventral views of elongating embryos later during epiboly. k, l Corresponding ventral views of an embryo during elongation with different combinations of fluorescence and/or DIC layers shown. m Right-lateral higher magnification views of an elongating embryo with inserts showing some of the ventral ciliated cells (shallow confocal stacks centered at the ventral midline). n, o Corresponding ventral views of embryos during organogenesis. Corresponding left lateral views of embryos during organogenesis p-q, r-s, t-u. Corresponding ventral views of early veliger stage embryos v-w, x-y. ltc left terminal cell. All other labels are the same as those used in Figs. 3, ,6, 6, and and10. 10. Scale bar equals 50 μm for a–l and n–y. Scale bar equals 25 μm for m and 20 μm for its inserts. Additional file 22: (16M, tiff)Figure S12. Behavior of posterior blastopore lip cells undergoing convergence and extension (3c 2, 3d 2 ). a–aa Projected confocal Z slices of embryos injected with dextran or di I, into 3c, 3d or their subclones, as indicated. a Ventral view of an embryo at epiboly stage. b–u Frames from a time-lapse of the same embryo as shown in a. b–l Frames from a time-lapse movie of the same embryo undergoing convergence and extension to zipper the posterior blastopore ( bp) closed. m–r Frames from the same movie showing membrane protrusions (arrows) and cilia (arrow heads) on the cells undergoing convergent extension (zippering). s, t Frames from the same movie showing that the cells undergoing convergence and extension are from the 3c 2 and 3d 2 cells. The asterisk (*) marks cells from the 3c 1 and 3d 1 clones that migrate anteriorly towards the ventral side of the stomodeum. In u, the 3c 211 and 3d 211 cells have entered the deeper parts of the mouth an are out of view of the stack, indicated by dashed lines. v–aa Live confocal images of post-zippering-stage embryos showing the movement of the 3c 221 and 3d 221 cells posteriorly, between cells of the 2d clone. bb–mm Images of fixed embryos stained for acetylated tubulin (to mark cilia) and DAPI (to mark DNA). bb, cc Shows ventral views ( vv) of embryos at the early stages of convergent extension and arrowheads point to cilia on cells at the posterior edge of the blastopore. dd–ff Ventral views of embryos during elongation. The ciliated left and right terminal cells ( ltc, rtc) are labeled. gg Posterior view ( pv) of the same embryo shown in ff. Scale bar in l and mm are equal to 50 μm; scale bar in v equals 20 μm. See also Additional files 9 and 10. Additional file 23: (15M, tiff)Figure S13. Origin of the anus (2d 2). Images of live embryos, with dextran and di I-labeled 4d, 3d, 3c, 2d, or 2d subclones, as indicated. In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion protein for the actin-binding domain of utrophin-GFP (UTPH) to visualize cell outlines, where indicated. Anterior is up in all cases. a–c Corresponding ventral views of embryos during organogenesis with different combinations of fluorescence and/or DIC layers shown. d, e Corresponding right-lateral (oblique-ventral) views of embryo during organogenesis. f, g Corresponding higher magnification right-lateral views of the posterior end of an embryo during organogenesis. h, i Corresponding ventral views of veliger stage embryo after the anus as opened. j Ventral view of a veliger stage embryo just before the anus opens. Note that the hindgut is somewhat swollen. k, l Corresponding ventral views of pre-veliger stage embryos. m, n Corresponding (oblique-ventral) left-lateral views of the pre-veliger stage embryos. o Ventral view of early veliger. p, q Corresponding (oblique-ventral) left-lateral views of an early veliger. r, s Corresponding ventral views of an early veliger. an anus, nc neural cell, ns neurosensory cell, rm right mantle, tcs terminal cells (called tc in Fig. 6 ). All other labels are the same as those used in Figs. 3, ,4, 4,,10, 10, and and11. 11. Scale bar equals 50 μm for a–e, h–s. Scale bar equals 25 μm in f, g. Additional file 24: (19M, tiff)Figure S14. Summary of second and third quartet clones. Columns show clones, colored as labeled, and according to those shown in Figs. 1 and and15. 15. Rows show time points as indicated at the far right. Top row shows animal views; all other rows show ventral views. The smaller, irregularly shaped, stippled cells of the 3a 2 and 3b 2 clones represent ecto-mesenchyme located below the ectoderm Additional file 25: (18M, tiff)Figure S15. Lineage diagram of second and third quartet micromeres and third quartet macromeres. Colors correspond to those given in Figs. 1 and and14 14. Additional file 26: (13M, tiff)Figure S16. Morphogenesis of the blastopore lip. a–e Vegetal/ventral views during gastrulation with the future anterior at the top of the figure. Time points are the same as those shown in rows 2–6 in Figs. 1 and and14: 14: a ~94 hpf, b ~99 hpf, c ~120–130 hpf, d ~130–137 hpf, e ~140–145hpf. The coloring shows the relative clonal contributions of cells within the embryo and to the blastopore lip. The blastopore lip is marked in each panel by a solid white line. The blastopore lip marks the boundary between the ectodermal micromere cap and the endoderm/endomesoderm/ectomesoderm. As gastrulation proceeds, some cells leave the blastopore lip, but remain on the surface, and these are marked by a dashed white line. The 2d cells are marked by a dashed yellow line in a, b, but are more difficult to follow in time points c–e and thus are not shown. The 3c 2 - and 3d 2 -derived terminal cells (TC) are marked with an asterisk to follow their migration after they leave the blastopore lip. Some cells of the blastopore lip move internally into the blastocoel/archenteron, and the solid white line can no longer be seen in some areas d, e. bp blastopore, em ectomesoderm (derived from 3a 2 and 3b 2 ). Go to: Footnotes Competing interests The authors declare that they have no competing interests. Authors’ contributions DCL and JQH designed and executed experiments, prepared figures, and co-wrote the first draft of the manuscript. KJP executed experiments and prepared figures. All authors contributed to revisions of the manuscript. All authors read and approved the final manuscript. Go to: Contributor Information Deirdre C. Lyons, Email: [email protected]. Kimberly J. Perry, Email: ude.sionilli@1rednajk. Jonathan Q. Henry, Email: ude.sionilli@4yrneh-j. Go to: References1. Stern CD. Gastrulation: from cells to embryo, Cold Spring Harbor Laboratory Press. 1 2004.2. Martindale MQ, Hejnol A. A developmental perspective: changes in the position of the blastopore during bilaterian evolution. Dev Cell. 2009; 17 :162–74. doi: 10.1016/j.devcel.2009.07.024. [ Pub Med] [ Cross Ref]3. Nielsen C. How to make a protostome. Invertebr Syst. 2012; 26 :25. doi: 10.1071/IS11041. [ Cross Ref]4. Satoh N, Tagawa K, Takahashi H. How was the notochord born? Evol Dev. 2012; 14 :56–75. doi: 10.1111/j.1525-142X.2011.00522.x. [ Pub Med] [ Cross Ref]5. Arendt D, Nübler-Jung K. Dorsal or ventral: similarities in fate maps and gastrulation patterns in annelids, arthropods and chordates. Mech Dev. 1997; 61 :7–21. doi: 10.1016/S0925-4773 (96)00620-X. [ Pub Med] [ Cross Ref]6. Martín-Durán JM, Janssen R, Wennberg S, Budd GE, Hejnol A. Deuterostomic development in the protostome Priapulus caudatus. Curr Biol. 2012; 22 :2161–6. doi: 10.1016/j.cub.2012.09.037. [ Pub Med] [ Cross Ref]7. Hejnol A, Martindale MQ. Mouth, the anus, and the blastopore—open questions about questionable openings - Oxford Scholarship. In: Telford MJ, Littlewood DTJ, editors. Anim Evol Genomes, Foss Trees. Oxford: Oxford University Press; 2009. pp. 33–40.8. Arendt D. Comparative aspects of gastrulation. In: Stern CD, editor. Gastrulation from cells to embryo. New York, NY: Cold Spring Harbor Laboratory Press; 2004.9. Chea HK, Wright CV, Swalla BJ. Nodal signaling and the evolution of deuterostome gastrulation. Dev Dyn. 2005; 234 :269–78. doi: 10.1002/dvdy.20549. [ Pub Med] [ Cross Ref]10. Lyons DC, Henry JQ: Ins and outs of spiralian gastrulation. Int J Dev Biol 2014, 58:413-28. [ Pub Med]11. Janssen R, Jörgensen M, Lagebro L, Budd GE. Fate and nature of the onychophoran mouth-anus furrow and its contribution to the blastopore. Proc Biol Sci. 2015;282. [ PMC free article] [ Pub Med]12. Van den Biggelaar JAM, Edsinger-Gonzales E, Schram FR: The improbability of dorso-ventral axis inversion during animal evolution as presumed by Geoffroy Saint Hilaire. Contrib to Zool 2002, 71: http://www.ctoz.nl/vol71/nr01/a03.13. Martindale MQ. Evolution of development: the details are in the entrails. Curr Biol. 2013; 23 : R25–8. doi: 10.1016/j.cub.2012.11.023. [ PMC free article] [ Pub Med] [ Cross Ref]14. Hejnol A. A twist in time–the evolution of spiral cleavage in the light of animal phylogeny. Integr Comp Biol. 2010; 50 :695–706. doi: 10.1093/icb/icq103. [ Pub Med] [ Cross Ref]15. Henry JQ: Spiralian model systems. Int J Dev Biol 2014, 58:389-401. [ Pub Med]16. Smith CM, Lans D, Weisblat DA. Cellular mechanisms of epiboly in leech embryos. Development. 1996; 122 :1885–94. [ Pub Med]17. Arenas-Mena C. Brachyury, Tbx2/3 and sall expression during embryogenesis of the indirectly developing polychaete Hydroides elegans. Int J Dev Biol. 2013; 57 :73–83. doi: 10.1387/ijdb.120056ca. [ Pub Med] [ Cross Ref]18. Chan XY, Lambert JD. Development of blastomere clones in the Ilyanassa embryo: transformation of the spiralian blastula into the larval body plan. Dev Genes Evol. 2014; 224 :159–74. doi: 10.1007/s00427-014-0474-z. [ Pub Med] [ Cross Ref]19. Boyle MJ, Yamaguchi E, Seaver EC. Molecular conservation of metazoan gut formation: evidence from expression of endomesoderm genes in Capitella teleta (Annelida) Evodevo. 2014; 5 :39. doi: 10.1186/2041-9139-5-39. [ PMC free article] [ Pub Med] [ Cross Ref]20. Halanych KM, Bacheller JD, Aguinaldo AM, Liva SM, Hillis DM, Lake JA. Evidence from 18S ribosomal DNA that the lophophorates are protostome animals. Science. 1995; 267 :1641–3. doi: 10.1126/science.7886451. [ Pub Med] [ Cross Ref]21. Dunn CW, Hejnol A, Matus DQ, Pang K, Browne WE, Smith SA, et al. Broad phylogenomic sampling improves resolution of the animal tree of life. Nature. 2008; 452 :745–9. doi: 10.1038/nature06614. [ Pub Med] [ Cross Ref]22. Hejnol A, Martindale MQ. Acoel development indicates the independent evolution of the bilaterian mouth and anus. Nature. 2008; 456 :382–6. doi: 10.1038/nature07309. [ Pub Med] [ Cross Ref]23. Arendt D, Technau U, Wittbrodt J. Evolution of the bilaterian larval foregut. Nature. 2001; 409 :81–5. doi: 10.1038/35051075. [ Pub Med] [ Cross Ref]24. Byrum CA, Martindale MQ. Gastrulation in Cnidaria and Ctenophora. In: Stern CD, editor. Gastrulation from cells to embryo. New York, NY: Cold Spring Harbor Laboratory Press; 2004.25. Technau U. Brachyury, the blastopore and the evolution of mesoderm. Bioessays. 2001; 23 :788–94. doi: 10.1002/bies.1114. [ Pub Med] [ Cross Ref]26. Technau U, Scholz CB. Origin and evolution of endoderm and mesoderm. Int J Dev Biol. 2003; 47 :531–9. [ Pub Med]27. Smart TI, von Dassow G. Unusual development of the mitraria larva in the polychaete Owenia collaris. Biol Bull. 2009; 217 :253–68. [ Pub Med]28. Hejnol A, Martín-Durán JM: Getting to the bottom of anal evolution. Zool Anzeiger - A J Comp Zool 2015, 256:61-74.29. Nielsen C. Trochophora larvae: cell-lineages, ciliary bands, and body regions. 1. Annelida and Mollusca. J Exp Zool B Mol Dev Evol. 2004; 302B :35–68. doi: 10.1002/jez.b.20001. [ Pub Med] [ Cross Ref]30. Henry JJ, Collin R, Perry KJ. The slipper snail, Crepidula: an emerging lophotrochozoan model system. Biol Bull. 2010; 218 :211–29. [ Pub Med]31. Hejnol A, Martindale MQ, Henry JQ. High-resolution fate map of the snail Crepidula fornicata: the origins of ciliary bands, nervous system, and muscular elements. Dev Biol. 2007; 305 :63–76. doi: 10.1016/j.ydbio.2007.01.044. [ Pub Med] [ Cross Ref]32. Henry JQ, Perry KJ, Martindale MQ. Cell specification and the role of the polar lobe in the gastropod mollusc Crepidula fornicata. Dev Biol. 2006; 297 :295–307. doi: 10.1016/j.ydbio.2006.04.441. [ Pub Med] [ Cross Ref]33. Henry JQ, Perry KJ, Martindale MQ. Beta-catenin and early development in the gastropod Crepidula fornicata. Integr Comp Biol. 2010; 50 :707–19. doi: 10.1093/icb/icq076. [ Pub Med] [ Cross Ref]34. Lyons DC, Perry KJ, Lesoway MP, Henry JQ. Cleavage pattern and fate map of the mesentoblast, 4d, in the gastropod Crepidula: a hallmark of spiralian development. Evodevo. 2012; 3 :21. doi: 10.1186/2041-9139-3-21. [ PMC free article] [ Pub Med] [ Cross Ref]35. Martindale MQ, Henry JQ. Modifications of cell fate specification in equal-cleaving nemertean embryos: alternate patterns of spiralian development. Development. 1995; 121 :3175–85. [ Pub Med]36. Henry JJ, Martindale MQ. Conservation of the spiralian developmental program: cell lineage of the nemertean, Cerebratulus lacteus. Dev Biol. 1998; 201 :253–69. doi: 10.1006/dbio.1998.8966. [ Pub Med] [ Cross Ref]37. Saunders LR, Mc Clay DR. Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition. Development. 2014; 141 :1503–13. doi: 10.1242/dev.101436. [ PMC free article] [ Pub Med] [ Cross Ref]38. Burkel BM, Von Dassow G, Bement WM. Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin. Cell Motil Cytoskeleton. 2007; 64 :822–832. doi: 10.1002/cm.20226. [ PMC free article] [ Pub Med] [ Cross Ref]39. Miller AL, Bement WM. Regulation of cytokinesis by Rho GTPase flux. Nat Cell Biol. 2009; 11 :71–7. doi: 10.1038/ncb1814. [ PMC free article] [ Pub Med] [ Cross Ref]40. Giani VC, Jr, Yamaguchi E, Boyle MJ, Seaver EC. Somatic and germline expression of piwi during development and regeneration in the marine polychaete annelid Capitella teleta. Evodevo. 2011; 2 :10. doi: 10.1186/2041-9139-2-10. [ PMC free article] [ Pub Med] [ Cross Ref]41. Molé-Bajer J, Bajer AS. Studies of selected endosperm cells with the light and electron microscope: the technique. Cellule. 1968; 67 :257–65.42. Conklin EG. The embryology of Crepidula. J Morphol. 1897; 13 :1–226. doi: 10.1002/jmor.1050130102. [ Cross Ref]43. Lartillot N, Lespinet O, Vervoort M, Adoutte A. Expression pattern of Brachyury in the mollusc Patella vulgata suggests a conserved role in the establishment of the AP axis in Bilateria. Development. 2002; 129 :1411–21. [ Pub Med]44. Rawlinson KA. Embryonic and post-embryonic development of the polyclad flatworm Maritigrella crozieri; implications for the evolution of spiralian life history traits. Front Zool. 2010; 7 :12. doi: 10.1186/1742-9994-7-12. [ PMC free article] [ Pub Med] [ Cross Ref]45. Younossi-Hartenstein A, Hartenstein V. The embryonic development of the polyclad flatworm Imogine mcgrathi. Dev Genes Evol. 2000; 210 :383–98. doi: 10.1007/s004270000086. [ Pub Med] [ Cross Ref]46. Lambert JD. Mesoderm in spiralians: the organizer and the 4d cell. J Exp Zool B Mol Dev Evol. 2008; 310 :15–23. doi: 10.1002/jez.b.21176. [ Pub Med] [ Cross Ref]47. Arenas-Mena C. Indirect development, transdifferentiation and the macroregulatory evolution of metazoans. Philos Trans R Soc Lond B Biol Sci. 2010; 365 :653–69. doi: 10.1098/rstb.2009.0253. [ PMC free article] [ Pub Med] [ Cross Ref]48. Boyer BC, Henry JQ, Martindale MQ. Dual origins of mesoderm in a basal spiralian: cell lineage analyses in the polyclad turbellarian Hoploplana inquilina. Dev Biol. 1996; 179 :329–38. doi: 10.1006/dbio.1996.0264. [ Pub Med] [ Cross Ref]49. Boyer BC, Henry JJ, Martindale MQ. The cell lineage of a polyclad turbellarian embryo reveals close similarity to coelomate spiralians. Dev Biol. 1998; 204 :111–23. doi: 10.1006/dbio.1998.9084. [ Pub Med] [ Cross Ref]50. Chan XY, Lambert JD. Patterning a spiralian embryo: a segregated RNA for a Tis11 ortholog is required in the 3a and 3b cells of the Ilyanassa embryo. Dev Biol. 2011; 349 :102–112. doi: 10.1016/j.ydbio.2010.10.001. [ Pub Med] [ Cross Ref]51. Nederbragt B, Lespinet O, van Wageningen S, van Loon AE, Adoutte A, Dictus WJAG. A lophotrochozoan twist gene is expressed in the ectomesoderm of the gastropod mollusk Patella vulgata. Evol Dev. 2002; 4 :334–43. doi: 10.1046/j.1525-142X.2002.02020.x. [ Pub Med] [ Cross Ref]52. Wu SY, Ferkowicz M, Mc Clay DR. Ingression of primary mesenchyme cells of the sea urchin embryo: a precisely timed epithelial mesenchymal transition. Birth Defects Res C Embryo Today. 2007; 81 :241–52. doi: 10.1002/bdrc.20113. [ Pub Med] [ Cross Ref]53. Meyer NP, Boyle MJ, Martindale MQ, Seaver EC. A comprehensive fate map by intracellular injection of identified blastomeres in the marine polychaete Capitella teleta. Evodevo. 2010; 1 :8. doi: 10.1186/2041-9139-1-8. [ PMC free article] [ Pub Med] [ Cross Ref]54. Woltereck R. Beiträge zur praktischen Analyse der Polygordius Entwicklung nach dem “Nordsee” – und dem “Mittelmeer” – Typus. I. Die für beide Typen gleichverlaufende Entwicklungsabschnitt: Vom Ei bis zum jüngsten Trochophora-Stadium. Arch Entw Mech Org. 1904; 18 :377–403.55. Steinmetz PRH, Zelada-Gonzáles F, Burgtorf C, Wittbrodt J, Arendt D, Zelada-Gonzales F. Polychaete trunk neuroectoderm converges and extends by mediolateral cell intercalation. Proc Natl Acad Sci USA. 2007; 104 :2727–32. doi: 10.1073/pnas.0606589104. [ PMC free article] [ Pub Med] [ Cross Ref]56. Gharbiah M, Nakamoto A, Nagy LM. Analysis of ciliary band formation in the mollusc Ilyanassa obsoleta. Dev Genes Evol. 2013; 223 :225–35. doi: 10.1007/s00427-013-0440-1. [ Pub Med] [ Cross Ref]57. Henry JQ, Hejnol A, Perry KJ, Martindale MQ. Homology of ciliary bands in spiralian trochophores. Integr Comp Biol. 2007; 47 :865–71. doi: 10.1093/icb/icm035. [ Pub Med] [ Cross Ref]58. Bhaud M, Cazaux C. Les larves de polychètes des côtes de France. Oceanis. 1982; 8 :57–160.59. Gravely F. Studies on polychaete larvae. Q J Microsc Sci. 1909; 53 :597–627.60. Nielsen C. Animal evolution. Oxford: Oxford University Press; 1995.61. Nielsen C. Animal phylogeny in the light of the trochaea theory. Biol J Linn Soc. 1985; 25 :243–99. doi: 10.1111/j.1095-8312.1985.tb00396.x. [ Cross Ref]62. Nielsen C. Structure and development of metazoan ciliary bands and their phylogenetic significance. Acta Zool. 1987; 68 :205–62. doi: 10.1111/j.1463-6395.1987.tb00892.x. [ Cross Ref]63. Strathmann RR. Hypotheses on the origins of marine larvae. Rev Ecol Syst. 1993; 24 :89–117. doi: 10.1146/annurev.es.24.110193.000513. [ Cross Ref]64. Dictus WJ, Damen P. Cell-lineage and clonal-contribution map of the trochophore larva of Patella vulgata (mollusca) Mech Dev. 1997; 62 :213–26. doi: 10.1016/S0925-4773 (97)00666-7. [ Pub Med] [ Cross Ref]65. Meyer NP, Seaver EC. Cell lineage and fate map of the primary somatoblast of the polychaete annelid Capitella teleta. Integr Comp Biol. 2010; 50 :756–67. doi: 10.1093/icb/icq120. [ Pub Med] [ Cross Ref]66. Robert A. Recherches sur le developpement des troques. Archs Zool Exp Gen. 1903; 10 :269–538.67. Rouse GW. Trochophore concepts: ciliary bands and the evolution of larvae in spiralian Metazoa. Biol J Linn Soc. 1999; 66 :411–464. doi: 10.1111/j.1095-8312.1999.tb01920.x. [ Cross Ref]68. Cantell CE. Some developmental stages of the peculiar nemertean larvae Pilidium recurvatum Fewkes from the Gullmarfjord (Sweden) Ark för Zool. 1967; 19 :143–7.69. Maslakova SA, von Dassow G. A non-feeding pilidium with apparent prototroch and telotroch. J Exp Zool Part B Mol Dev Evol. 2012; 318B :586–90. doi: 10.1002/jezb.22467. [ Pub Med] [ Cross Ref]70. Child CM. The early development of Arenicola and Sternaspis. Wilhelm Roux Arch fur Entwicklungsmechanik der Org. 1900; 9 :587–722. doi: 10.1007/BF02156195. [ Cross Ref]71. Mead AD. The early development of marine annelids. J Morphol. 1897; 8 :227–327. doi: 10.1002/jmor.1050130202. [ Cross Ref]72. Treadwell AL. The cytogeny of Podarke obscura (Verrill) J Morphol. 1901; 17 :399–486. doi: 10.1002/jmor.1050170304. [ Cross Ref]73. Wierzejski A. Embryologie von Physa fontinalis L. Z Wiss Zool. 1905; 83 :502–706.74. Kingsley EP, Chan XY, Duan Y, Lambert JD. Widespread RNA segregation in a spiralian embryo. Evol Dev. 2007; 9 :527–39. doi: 10.1111/j.1525-142X.2007.00194.x. [ Pub Med] [ Cross Ref]75. Le Gouar M, Lartillot N, Adoutte A, Vervoort M. The expression of a caudal homologue in a mollusc, Patella vulgata. Gene Expr Patterns. 2003; 3 :35–7. doi: 10.1016/S1567-133X (02)00091-1. [ Pub Med] [ Cross Ref]76. Perry, KJ, Lyons, DC Fischer, AHL, Helfrich, LW, Johansson, KB, Diamond, JC, Henry, JQ. Deployment of regulatory genes during gastrulation and germ layer specification in a model spiralian mollusc Crepidula. Dev Dyn, doi:10.1002/dvdy.24308. [ Pub Med]
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[
"Evo Devo.",
"2015; 6: 24.",
"Published online 2015 Jun 24. doi: 10.1186/s13227-015-0019-1PMCID: PMC4673862Spiralian gastrulation: germ layer formation, morphogenesis, and fate of the blastopore in the slipper snail Crepidula fornicata Deirdre C. Lyons, Kimberly J. Perry, and Jonathan Q. Henry Author information ► Article notes ► Copyright and License information ►This article has been cited by other articles in PMC.",
"Go to: Abstract Background Gastrulation is a critical step in bilaterian development, directly linked to the segregation of germ layers, establishment of axes, and emergence of the through-gut.",
"Theories about the evolution of gastrulation often concern the fate of the blastopore (site of endomesoderm internalization), which varies widely in a major branch of bilaterians, the Spiralia.",
"In this group, the blastopore has been said to become the mouth, the anus, both, or neither.",
"Different developmental explanations for this variation exist, yet no modern lineage tracing study has ever correlated the position of cells surrounding the blastopore with their contribution to tissues of the mouth, foregut, and anus in a spiralian.",
"This is the first study to do so, using the gastropod Crepidula fornicata.",
"Results Crepidula gastrulation occurs by epiboly: the first through third quartet micromeres form an epithelial animal cap that expands to cover vegetal endomesodermal precursors.",
"Initially, descendants of the second and third quartet micromeres (2a–2d, 3a–3d) occupy a portion of the blastopore lip.",
"As the blastopore narrows, the micromeres’ progeny exhibit lineage-specific behaviors that result in certain sublineages leaving the lip’s edge.",
"Anteriorly, cells derived from 3a 2 and 3b 2 undergo a unique epithelial-to-mesenchymal transition involving proliferation and a collective movement of cells into the archenteron.",
"These cells make a novel spiralian germ layer, the ectomesoderm.",
"Posteriorly, cells derived from 3c 2 and 3d 2 undergo a form of convergence and extension that involves zippering of cells and their intercalation across the ventral midline.",
"During this process, several of these cells, as well as the 2d clone, become displaced posteriorly, away from the blastopore.",
"Progeny of 2a-2c and 3a-3d make the mouth and foregut, and the blastopore becomes the opening to the mouth.",
"The anus forms days later, as a secondary opening within the 2d 2 clone, and not from the classically described “anal cells”, which we identify as the 3c 221 and 3d 221 cells.",
"Conclusions Our analysis of Crepidula gastrulation constitutes the first description of blastopore lip morphogenesis and fates using lineage tracing and live imaging.",
"These data have profound implications for hypotheses about the evolution of the bilaterian gut and help explain observed variation in blastopore morphogenesis among spiralians.",
"Electronic supplementary material The online version of this article (doi:10.1186/s13227-015-0019-1) contains supplementary material, which is available to authorized users.",
"Keywords: Spiralia, Lophotrochozoa, Blastopore, Ectomesoderm, Endomesoderm, Epiboly, Gastrulation, Amphistomy Go to: Background Gastrulation accomplishes several tasks that are critical for metazoan development, most importantly the segregation of germ layers and re-arrangement of cells to form the basic body-plan [ 1 ].",
"Germ layer segregation occurs when ectodermal, endodermal, and mesodermal cells adopt distinct gene regulatory states; morphogenetic events internalize endodermal and mesodermal cell types.",
"Because the basic body-plan is often established by the end of gastrulation, theories explaining body-plan evolution often suggest that body-plan divergence was driven in part by modifications to gastrulation events themselves (e.g., [ 2 – 5] and references therein).",
"For example, several evolutionary theories concern the site of gastrulation, a transient embryonic location where endoderm and mesoderm are internalized, called the blastopore [ 2, 3, 5 – 7 ].",
"The fate of the blastopore was traditionally used as a character for building taxonomic trees, separating protostomes (in which the blastopore becomes the opening to the mouth) from deuterostomes (in which the mouth forms separately from the blastopore, and the latter often becomes the anus) (reviewed in [ 2, 6 – 8 ]).",
"Although the terms deuterostome and protostome are still in our vernacular, they have lost much of their phylogenetic significance because cladistic analyses based on molecular characters (which are independent of morphology) show that protostomy and deuterostomy are not a reliable diagnostic character for major clades of bilaterians.",
"Deuterostomy appears to be ancestral for the Ambulacaria and Chordata [ 1, 9 ], but among the groups traditionally thought to belong to a protostome branch—the Ecdysozoa and Spiralia (which includes the Lophotrochozoa)—the fate of the blastopore is more complex and variable [ 7, 10, 6, 11 ].",
"Depending on the species, the blastopore has been reported to become the mouth (protostomy), the anus (deuterostomy), both mouth and anus (amphistomy), or neither (i.e., the blastopore closes).",
"Debate remains about how this diversity in blastopore fate arose, whether the differences have any influence on body-plan divergence, and even if the blastopore can be properly homologized between distantly related animals [ 2, 5, 7, 8, 10, 12, 13 ].",
"To resolve these debates, it is necessary to compare gastrulation in multiple species, in the context of a solid phylogenetic framework.",
"Spiralian lophotrochozoans offer a means to address many of these questions because although the fate of the blastopore varies between species, they share a stereotyped early cleavage pattern and fate map [ 14, 15 ].",
"These attributes make it possible to identify unambiguously homologous cell lineages, allowing direct comparison of cells around the blastopore.",
"Yet, few modern studies have leveraged spiralians’ unique strengths for investigating gastrulation [ 16 – 19 ].",
"Here, we study gastrulation in a representative spiralian species, the slipper snail Crepidula fornicata.",
"The Spiralia is a large and morphologically diverse assemblage of roughly 14 phyla [ 20, 21, 15 ].",
"Many members of this group, including annelids, molluscs, platyhelminthes, and nemerteans, exhibit a highly conserved pattern of embryonic cell divisions termed “spiral cleavage” [ 15, 14 ].",
"The fate map, birth order, and geometry of cells are so conserved between these animals that it is possible to compare homologous lineages, with single-cell resolution, between spiralians with vastly different larval and adult morphologies.",
"During gastrulation, spiralians transition from the highly conserved spiralian cleavage program to their species-specific body-plans.",
"Thus, spiralians are an excellent group for testing if there is indeed a relationship between varying gastrulation modes (e.g., the fate of the blastopore) and body-plan evolution.",
"Furthermore, because spiral cleavage is considered ancestral for the Spiralia as a whole [ 14 ], studying gastrulation in these species can inform us about how gastrulation, and body-plans, might have evolved in metazoans.",
"The blastopore is important to these arguments because, typically, it is ontogenetically linked to the openings of the digestive tract [ 2, 5, 7, 8, 10, 22, 23 ].",
"For example, in anthozoan cnidarians and ctenophores, the blastopore forms at the embryonic animal pole and matures into a dual-function, single orifice for feeding and excretion [ 24 ].",
"In deuterostomes, the blastopore forms at the vegetal pole and matures into the anus, while the mouth forms later, at a separate site within ventral anterior ectoderm [ 9 ].",
"Among the Ecdysozoa and Spiralia, the blastopore also forms at the vegetal pole, but its subsequent morphogenesis and fate is more complex and variable [ 6 – 8, 10, 12, 25 – 28 ], complicating discussions about the ancestral mode of gastrulation in these groups.",
"Compounding this problem is the fact that most of the work on spiralian gastrulation is based on classical descriptions from over 100 years ago [ 5, 7, 8, 29 ], long before intracellular lineage tracing or time-lapse imaging were possible.",
"The accuracy of these original descriptions comes into question, especially when concerning with the relationship between the blastopore and the formation of the mouth and anus; both can form days after the blastopore exists, making it very difficult to follow cell clones without modern intracellular lineage tracing.",
"Only a few previous lineage tracing studies have examined gastrulation in spiralians, most notably in the leech Helobdella robusta [ 16 ], and in the snail Ilyanassa obsoleta [ 18 ].",
"However, these studies did not focus on the behavior or fate of the blastopore per se.",
"The slipper snail C. fornicata is an emerging model system for developmental and evolutionary studies in spiralians [ 30 – 34 ].",
"Previously, a fate map was generated for every cell present in the four-principle quartets of animal micromeres, and the vegetal macromeres, for their respective contributions to the tissues of the veliger larva [ 31 ].",
"Here, we used lineage tracing, and time-lapse imaging, to present the first detailed examination of germ layer formation and morphogenesis of cells surrounding the blastopore during gastrulation in Crepidula.",
"Gastrulation occurs by epiboly, as animal cap micromeres expand to cover vegetal territories.",
"Later, the vegetal endodermal cells re-arrange to form a cavity that becomes part of the embryonic digestive tract, the archenteron.",
"To make it possible to directly homologize gastrulation events between species, we distinguish between the blastopore and blastopore lip.",
"At early epiboly stages, we define the blastopore as the endoderm/mesoderm cells themselves, and later as the hole/lumen of the archenteron.",
"We define the blastopore lip as those cells that give rise exclusively to ectodermal cells that are initially in direct contact with the endodermal/endomesodermal cells.",
"Here, we document specific lineage contributions to the anterior and posterior ends of the digestive tract (including mouth, foregut, and anus), which are derived from cells of the second and third quartet micromeres that occupied the blastopore lip.",
"In addition, we found that ectomesoderm arises from specific third quartet cells (3a 2 and 3b 2) that are situated at the anterior blastopore and become internalized by an epithelial to mesenchymal transition.",
"During gastrulation, blastopore lip cells exhibit extensive cell re-arrangement.",
"The posterior lip of the blastopore closes by a form of convergence and extension that involves zippering of cells derived from the third quartet (from 3c 2 and 3d 2 ).",
"The cells that undergo convergence and extension give rise to a line of ciliated ectodermal cells along the ventral midline, which we argue includes cells akin to the neurotroch and telotroch described in other spiralians.",
"The two posterior-most ciliated cells derived from these clones on the ventral midline were classically described by Conklin [ 34] as the “anal cells.” However, we found that these cells do not give rise to the anus, and so we renamed them the “terminal cells.” The anus arises from progeny of 2d 2, and as a result of convergence and extension, these cells become excluded from the posterior blastopore lip.",
"The anus thus forms from a secondary opening, and not from the blastopore, at 12 days of development.",
"The blastopore becomes the opening to the mouth.",
"We discuss the implications of these results for debates about the evolution of the blastopore in metazoans.",
"Go to: Methods Animal care and handling Stacks of adult C. fornicata were obtained from the Marine Resources Department at the Marine Biological Laboratory (Woods Hole, MA.",
"USA).",
"Adults were obtained from local waters by dredging during late winter months (January to March) and maintained in cold running seawater at approximately 12 °C to prevent egg laying.",
"The gravid females are stimulated to lay eggs by transferring them to warm water sea tables at 18–22 °C, as needed throughout the summer.",
"Embryos were obtained and reared, as previously described [ 30 – 34 ].",
"Briefly, the de-capsulated eggs and embryos were raised at room temperature (approx.",
"20 °C) in gelatin-coated Petri dishes containing 0.2-μm-filtered seawater with penicillin (100 U/ml, Sigma, St Louis, MO) and streptomycin sulfate (200μg/ml, Sigma, St Louis, MO).",
"Lineage tracing Specific cells were pressure microinjected with fluorescent lineage tracers, as previously detailed, to follow their contributions to specific germ layers, the blastopore, mouth, foregut, and anus (Rhodamine Green Dextran, cat # D-7153, or Di IC18 (3), cat # D-282, Life Technologies, Grand Island, NY; [ 31, 33 – 36 ].",
"In some cases, multiple cells were injected, and sub-lineages were followed, by sequential injection of two cells with these different tracers.",
"All second and third quartet micromeres (Fig.",
"1a – h; Additional file 11: Figure S1) were individually microinjected to follow their behavior during the process of gastrulation (Figs.",
"2, Additional file 12: Figure S2; S2;3, 3, Additional file 13: Figure S3; S3;4, 4, Additional file 14: Figure S4;S4;5, 5, Additional file 15: Figure S6; S6;6, 6, Additional file 16: Figure S6; S6;7, 7, Additional file 17: Figure S7; S7;8, 8, Additional file 18: Figure S8; S8;9,Additional 9 ,Additional file 19: Figure S9; S9;10, 10, Additional file 20: Figure S10; S10;11, 11, Additional file 21: Figure S11; and and12, 12, Additional file 22: Figure S12;) and their contributions to the formation of various germ tissues and the gut (Figs.",
"13, Additional file 23: Figure S13; S13;14, 14, Additional file 24: Figure S14; and and15, 15, Additional file 25: Figure S15).",
"For each micromere, the two daughter cells (i.e., 2a 1 and 2a 2 or 3a 1 and 3a 2 cells) were also labeled independently (a total of 16 sub-lineages; Figs.",
"14 and and15).",
"15 ).",
"A minimum of five embryos were scored, in the live embryo, for each clone examined, and these were all found to be highly regular.",
"Fig.",
"1Early epiboly and position of clones at the blastopore lip.",
"a–h Cartoons of early embryo with second and third quartet micromeres colored, as indicated in key to the right.",
"a–c Animal pole views; d is a ventral/vegetal view; e–h ...",
"Fig.",
"2Narrowing of the blastopore during later epiboly, and formation of the mouth/stomodeum.",
"a–e Confocal images of living embryos expressing UTPH-GFP to mark the actin cytoskeleton, and histone H2B-RFP to mark the nuclei.",
"Ventral views are shown during ...",
"Fig.",
"3Fates of micromere 2a, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos with dextran- and di I-labeled 2a, or 2a subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"4Fates of micromere 2b, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 2b, or 2b subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"5Fates of micromere 2c, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos with dextran and di I labeled 2c, or 2c subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"6Fates of micromere 2d, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 2d, or 2d subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"7Fates of micromere 3a, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3a, or 3a subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"8Fates of micromere 3b, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3b, or 3b subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"9Behavior of ectomesoderm (3a 2, 3b 2).",
"a–i Time-lapse movie of an embryo injected with utrophin-GFP (UTPH) to mark cell outlines, and histone H2B-RFP (H2B) to mark nuclei, where indicated.",
"Ventral view.",
"bp blastopore.",
"Several unidentified (x) daughter ...",
"Fig.",
"10Fates of micromere 3c, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3c, or 3c subclones, as indicated.",
"Animal pole is up in a and b. Anterior is up in c–t.",
"a, b Dorso-lateral ...",
"Fig.",
"11Fates of micromere 3d, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3d, or 3d subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent ...",
"Fig.",
"12Behavior of posterior blastopore lip cells undergoing convergence and extension (3c 2, 3d 2 ).",
"a–aa Projected confocal Z slices of embryos injected with dextran or di I, into 3c, 3d or their subclones, as indicated.",
"a Ventral view of an embryo at ...",
"Fig.",
"13Origin of the anus (2d 2).",
"Images of live embryos, with dextran and di I-labeled 4d, 3d, 3c, 2d, or 2d subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion protein for the actin-binding domain ...",
"Fig.",
"14Summary of second and third quartet clones.",
"Columns show clones, colored as labeled, and according to those shown in Figs.",
"1 and and15.",
"15.",
"Rows show time points as indicated at the far right.",
"Top row shows animal views; all other rows ...",
"Fig.",
"15Lineage diagram of second and third quartet micromeres and third quartet macromeres.",
"Colors correspond to those given in Figs.",
"1 andand14 14Fluorescently tagged protein expression To help distinguish individual cells and their nuclei in live embryos, we microinjected synthetic m RNAs to express various combinations of fluorescently tagged proteins (Fig.",
"1 ).",
"None of the constructs used contain Crepidula -specific sequence, yet they are expressed robustly, and fluorescence was detected within a few hours of injection.",
"DNA in the nuclei was followed using histone H2B-RFP (H2B-RFP) and histone H2B-GFP (H2B-GFP) fusions, while plasma membrane was followed with an RFP-membrane fusion (MEM-GFP).",
"These clones were the gift of the Mc Clay lab, Duke University [ 37 ].",
"We followed live F-actin using a GFP fusion of the actin-binding domain of utrophin (UTPH-GFP) and live microtubules using GFP or RFP fusions of the MT binding domain of ensconsin (EMTB-3x GFP).",
"These clones were the gift of the Bement Lab (University of Wisconsin) [ 38, 39] and are now available commercially ( https://www.addgene.org/26737/; https://www.addgene.org/26741/ ).",
"Synthetic m RNAs were generated from linearized plasmids using the m Message m Machine kit (Life Technologies, Grand Island, NY) and purified with RNeasy Min Elute Cleanup kit (Qiagen, Valencia, CA).",
"Stock concentrations of these individual m RNAs ranged from 1 to 2 μg/μl in RNAse-free sterile d H 2 O. RNAs were diluted to a working concentration of 300–500 μg/μl.",
"To visualize the solutions as they were being injected, the RNAs were mixed with a sterile filtered RNAse-free solution of 0.5 % phenol red, (1 part phenol red solution, cat.",
"#P0292, Sigma, St Louis, MO, to 2 or 3 parts RNA solution).",
"In this manner, a faint red cloud can be visualized inside the zygote during injection.",
"Synthetic m RNAs were microinjected into fertilized eggs prior to first cleavage and approximately 5–10 % of the cell’s volume was injected.",
"When the fertilized eggs are first collected, it is not possible to know exactly when first cleavage will take place.",
"If the injections are carried out too soon before first cleavage, some graded/mosaic level of expression may be noted at later stages.",
"The latter cases were not used for further study.",
"Visible levels of expression can first be detected under a fluorescence dissecting scope around the four- to eight-cell stages.",
"Fixation and histology Embryos and larvae were fixed in a 3.7 % solution of ultrapure formaldehyde (made using the manufacturer’s 10 % stock solution, Ted Pella, Inc., Redding, CA, USA) dissolved in FSW with added Instant Ocean Aquarium Sea Salt Mixture (United Pet Group, Blacksburg, VA, USA) to adjust for the reduced osmolarity (0.47 gm added per 50 ml of final working volume).",
"Embryos were fixed for 1 h at room temperature and rinsed three times in sterile 1× PBS (1× PBS:1.86m M Na H 2 PO 4, 8.41m M Na 2 HPO 4, 175m N Na Cl, p H 7.4), followed by three washes in 100 % methanol before storage at −80 °C.",
"Acetylated tubulin antibody labeling (1:400, cat #T7451, Sigma, St. Louis) followed the method described in [ 40 ].",
"A solution of 0.5 μg/ml DAPI (Life Technologies, Grand Island, NY) dissolved in 1× PBS was applied to embryos following antibody labeling to visualize nuclei.",
"Embryos were incubated in the dark for 10 min, followed by three washes in 1× PBS/0.1 % Tween, and stored in 80 % glycerin/20 % 1× PBS at 4 °C until imaging.",
"Microscopy Live embryos expressing fusion proteins, or labeled with traditional lineage tracers (di I or dextrans), were mounted in filtered seawater between Rain-X-coated (ITW Global Brands, Houston, TX) glass slides and coverslips supported by tiny clay feet (Van Aken Plastalina, Rancho Cucamonga, CA, USA).",
"For long-term time-lapse imaging, the coverslips were sealed with molten VALAP to prevent desiccation [ 41 ].",
"For time-lapse, embryos were imaged every 5–10 min for anywhere from 4 to 48 h. Widefield images were captured with a Zeiss Axio Imager 2 (Carl Zeiss Inc., Munich, Germany).",
"Scanning confocal imaging was carried out with an inverted Zeiss LSM 700, Zeiss LSM 780, and Zeiss Cell Observer spinning disc microscopes (Carl Zeiss Inc., Munich, Germany).",
"Light sheet imaging was carried out with a Zeiss Light Sheet.",
"Z1 (Carl Zeiss Inc., Munich, Germany).",
"For image processing, Z-stacks were prepared to make maximum projections with Fiji and Image J software (National Institutes of Health, Bethesda, MD, USA) or the focus stacking software Helicon Focus (Helicon Soft Ltd., Kharkov, Ukraine).",
"Fixed embryos labeled with antibodies were placed on Rain-X-coated (ITW Global Brands, Houston, TX) glass slides in 80 % glycerol/20 % 1× PBS.",
"Coverslips were first prepared with small supporting feet made from plastic “Tough Spots” adhesive labels (Diversified Biotech, Boston, MA, USA).",
"These adhesive labels were trimmed into 1–2-mm squares, stacked three layers thick, and adhered to the four corners of glass coverslips to prevent the embryos from being crushed.",
"Specimens were visualized on a Zeiss Axioplan microscope (Carl Zeiss Inc., Munich, Germany), and imaging was conducted with a Spot Flex camera (Spot Imaging Solutions, Sterling Heights, Michigan).",
"Image stacks were combined and flattened using Helicon Focus (see above).",
"Go to: Results Behavior of cells during cleavage and early epiboly Early development in Crepidula has been described by Conklin [ 42] and Hejnol et al.",
"[ 31] (see also [ 30 ]).",
"The fertilized egg undergoes two rounds of orthogonal, equal cleavage occurring parallel to the animal-vegetal axis, giving rise to four blastomeres (macromeres) founding embryonic quadrants A, B, C, and D. These macromeres undergo several rounds of highly asymmetric cleavages that give rise to four tiers of smaller micromere quartets (“q”) at the animal pole: 1a–1d (1q), 2a–2d (2q), 3a–3d (3q), and 4a–4d (4q) (Fig.",
"1a–h; Table 1 ).",
"As each micromere quartet is born, the sister quartets’ vegetal macromeres (“Q”) are renamed: 1A–1D (1Q); 2A–2D (2Q); 3A–3D (3Q), and 4A–4D (4Q).",
"The embryo is radially symmetric up through the early 24-cell-stage (when the first three quartets have been born).",
"Symmetry is broken at approximately 27 h past fertilization (hpf) at 20 °C, when the 3D macromere divides precociously, giving rise to the 4d micromere at the 25-cell stage (Fig.",
"1a ).",
"At approximately 33 hpf, 4d divides bilaterally to form left and right teloblasts (ML and MR) which produce endoderm and mesoderm (“endomesoderm,” Fig.",
"1b ).",
"Table 1Crepidula fornicata staging system A fate map of these teloblasts has recently been established up through their fifth division [ 34 ].",
"Thus, the well-defined cleavage pattern of the 4d lineage can be used to quickly orient the embryo during early, spherical or “round” stages of gastrulation (Fig.",
"1; Table 1 ).",
"We found that some fluorescent biosensors, particularly actin (Fig.",
"1q) and membrane sensors (Fig.",
"1t ), appear brightest in the 4d lineage and thus can be used to assess the age and orientation of embryos, even in the absence of specific cells being directly labeled.",
"The 4d micromere is born as a tear-shaped cell with its pointed end directed towards the center of the embryo, which is covered by the micromere cap (Fig.",
"1a–i ).",
"The rounded end is initially exposed at the surface of the embryo, as it is not yet covered fully by the micromere cap.",
"All of its mesodermal derivatives, and some of its endodermal derivatives, will be born from the more pointed, internal end, and thus those cells are internalized at birth (Fig.",
"1k–q ).",
"In contrast, the larger rounded, exposed area of the 4d cell is where the future 1m L/R and 3m L/R endodermal lineages will be born (Fig.",
"1c ).",
"At first, the micromere cap does not fully cover these cells, but they will be covered during epiboly (99 hpf, Fig.",
"1c–d and o–q; Table 1 ).",
"At approximately 47 hpf, the 3A–3C macromeres divide to form the 4a–4c micromeres (Table 1 ).",
"Following this period of early cleavage divisions, the embryo undergoes compaction and assumes a tight spherical shape (Fig.",
"1k, p, r; Table 1 ).",
"The micromere-derived animal cap gradually expands to cover more surface area (Fig.",
"1q–w ), and by 60 hpf, the animal cap covers 50–55 % of the spherical surface having reached its widest circumference at the equator of the embryo (Fig.",
"1r; Table 1 ).",
"Cellular behavior during gastrulation: epiboly of the micromere cap While we do not fully understand the mechanisms that regulate expansion of the micromere cap, it likely involves continued cell divisions (Fig.",
"1s–w) and thinning of micromere cap progeny.",
"As the animal cap expands, it covers more of the endomesodermal lineages (Figs.",
"1 and and2).",
"2 ).",
"At 91 hpf, the spherical embryo begins to change shape as gastrulation continues to take place by the process of epiboly.",
"At this time, the embryo begins to flatten noticeably along the animal-vegetal axis (Fig.",
"1h, ,p; p; Table 1 ).",
"The edge of the cap (derived from the second and third quartet micromeres, the colored lineages in Fig.",
"1a–h) can just begin to be observed when viewed from the flattened vegetal pole, which can be seen in Fig.",
"2f.",
"At this stage, the animal cap covers approximately 65 % of the surface of the embryo.",
"Time-lapse movies of embryos expressing fluorescent membrane (MEM-RFP) or actin cytoskeleton (UTPH-GFP) biosensors did not show obvious lamellipodial or filopodial extensions during animal cap expansion (see Fig.",
"1s–w; Fig.",
"2f, and Additional files 1 and 2 ).",
"This initial expansion of the micromere cap correlates with cell divisions in the epithelium (Fig.",
"1s–w ), which generates an increasingly larger number of smaller cells, and correlates with the flattening or thinning of this layer of cells (e.g., Fig.",
"1i, k, n, r, o, q ).",
"After reaching the equator, the micromere cap begins to constrict towards the vegetal pole (Fig.",
"2 ), advancing over the 4Q macromeres and 4q micromeres for the next 50 h as the blastopore narrows (Fig.",
"2a–b and f–h; Table 1 ).",
"During this process, the embryos become irregularly shaped as the internal macromeres and fourth quartet micromeres begin to undergo divisions (beginning at approximately 99 hpf; Fig.",
"2b, g, h ).",
"At this time, the four macromeres divide equally, and Conklin [ 42] referred to this as the formation of a “fifth quartet.” Divisions are oriented such that the internal fourth quartet macromeres and micromeres ultimately assume a rectangular packing arrangement.",
"The embryo then elongates, which begins by 117 hpf, and the embryo assumes a flattened rectangular shape (Fig.",
"2b, ,h; h; Additional files 3 and 4; Table 1 ).",
"Throughout these stages, a noticeable depression, which becomes the embryonic gut or archenteron, can be seen at the site of the blastopore.",
"By 120 hpf, the embryo has assumed a more rounded, short ellipsoidal form, with the elongated axis corresponding to the future anterior-posterior axis (Fig.",
"2c, ,h h – i ).",
"The blastopore begins to be displaced towards the anterior end of the embryo by 141 hpf (Fig.",
"2d – e, ,i; i; Additional file 5 ).",
"Most of the elongation appears to occur in the post-trochal region, and as a consequence, the blastopore is displaced in an anterior direction (Table 1 ).",
"Though Conklin [ 42] reported that the blastopore temporarily closes deep within its recess, we have not observed this.",
"Our observations indicate that an external opening persists throughout the process of gastrulation, and during this process, the macromeres can be seen within it.",
"This opening ultimately becomes the mouth (Fig.",
"2d – e ).",
"By elongation stages, gastrulation has been completed and the process of organogenesis begins to unfold (Table 1 ).",
"Overt signs of organogenesis can be seen by 170 hpf, when the rudiments of the velar lobes, foot, and shell gland can be clearly seen (Figs.",
"3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, and and13).",
"13 ).",
"After several more weeks, advanced veliger larvae hatch and enter the water column where they begin to feed and ultimately settle to undergo metamorphosis to form juvenile snails.",
"The fates of cells around the blastopore Although a fate map was previously generated for each cell up through the 25-cell stage [ 31 ], those fates were related only to the tissues present within the veliger larvae.",
"That preliminary work established the basic germ layer derivatives of those embryonic cells, but did not describe the behavior of lineages during gastrulation.",
"In particular, we were interested in where these clones were situated relative to the blastopore.",
"Thus, we labeled individual second and third quartet micromeres, and some of their progeny, and observed their behavior during gastrulation.",
"We also followed their contributions to specific tissues, including the ectomesoderm and ectodermal components of the digestive tract, such as the mouth, esophagus, and the anus (Figs.",
"3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, ,13, 13, ,14, 14, and and15 15 ).",
"Labeling individual clones was necessary to understand how cells behave near the blastopore.",
"Lineage tracing results are described below for each of the 2q and 3q micromeres, as well as their immediate progeny 2q 1 /2q 2 and 3q 1 /3q 2, representing a total of 16 clones (Figs.",
"3, ,4, 4, ,5, 5,,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, ,13, 13, ,14, 14, and and15).",
"15 ).",
"As specified by Conklin [ 42 ], the daughters situated in a clockwise position around the animal-vegetal axis (as viewed from the animal pole), or those located closer to the animal pole, carry the superscript 1 (e.g., 2a 1 ).",
"Those situated in a counter-clockwise location, or situated closer to the vegetal pole, carry the superscript 2 (e.g., 2a 2 ).",
"Individual clones are shown in Figs.",
"3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, and and13 13 for different developmental stages described in Table 1.",
"A schematic diagram summarizing the relationships of these clones for six different stages of development between 18 and 145 hpf is also shown in Fig.",
"14.",
"A lineage diagram showing the ultimate fate of these clones is also shown in Fig.",
"15.",
"Time-lapse movies were also prepared to capture the dynamic behavior of certain cells (Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 ).",
"These analyses influenced how we defined the blastopore in Crepidula.",
"Definitions of “blastopore” can vary between animals, referring alternatively to the literal hole into which endoderm/mesoderm move, or to the endodermal and mesodermal cells themselves, or to cells surrounding the hole [ 2, 10, 13, 25 ].",
"To avoid confusion and enable direct comparisons with other species, we distinguish between the blastopore (the hole) and the cells surrounding that hole—which we call the blastopore lip (Fig.",
"16, Additional file 26: Figure S16).",
"These definitions became necessary because of the nature of epiboly, since gastrulation begins when the ectodermal cap spreads over the macromeres, but it is not until later stages that the endodermal/mesodermal tissues themselves re-arrange to form an archenteron and a literal hole (Fig.",
"16; Table 1 ).",
"Additionally, even after an obvious blastopore hole forms, the cells surrounding it change through cell rearrangement.",
"Fig.",
"16Morphogenesis of the blastopore lip.",
"a–e Vegetal/ventral views during gastrulation with the future anterior at the top of the figure.",
"Time points are the same as those shown in rows 2–6 in Figs.",
"1 andand14: 14: a ~94 hpf, ...",
"In Crepidula, during early stages of gastrulation, the blastopore consists of endodermal/endomesodermal precursors derived from the fourth quartet macromeres (4A-4D) and fourth quartet micromeres (4a-4cd) (Fig.",
"16a – b ); at later stages of gastrulation the blastopore is an actual hole/cavity leading inside of the embryo, and is surrounded by cells of the developing archenteron (Fig.",
"16c – e ).",
"The blastopore lip is made up of progeny derived from each of the second and third quartet micromeres that give rise to ectoderm exclusively (Figs.",
"14 and and16, 16, dashed white line).",
"This boundary between ectoderm and endoderm was defined through our detailed lineage analysis during gastrulation stages.",
"For example, initially, we assumed that the edge of the micromere cap (colored cells in Fig.",
"1d) was exactly equivalent to the blastopore lip, but lineage tracing of the 3a and 3b cells showed that the 3a 2 and 3b 2 sublineages make mesoderm (Figs.",
"14 and and15), 15 ), and so we had to adjust our delineation of the blastopore lip to run between the 3a 2 /3a 1 and 3b 2 /3b 1 clones (compare Figs.",
"1d and 16a ).",
"The second quartet (2a and 2c)All four of the second quartet micromeres give rise to progeny that lie along the lip of the blastopore (Fig.",
"14 ).",
"After their first division, specific daughters of these cells mainly lie along the blastopore lip (2a 1, 2b 2, 2c 2, and 2d 1 and 2d 2 cells; Figs.",
"3a, ,5a, 5a, and and14).",
"14 ).",
"2a and 2c give rise to bilaterally symmetrical clones of ectodermal cells that extend to the left and right sides of the embryo, respectively (Figs.",
"3b – j and and5c 5c – j ).",
"For the most part, their daughters, 2a 2 and 2c 1, make mirror symmetrical contributions to the development of the mouth (Figs.",
"3j, ,5j, 5j, ,14, 14, and and15).",
"15 ).",
"Both of these cells also extend a long thin line of cells from the developing blastopore/mouth in a bilaterally symmetrical fashion, which generate the left and right secondary ciliary band (i.e., the metatroch; Figs.",
"3 and and5).",
"5 ).",
"These cells also form much larger separated posterior, dorsolateral clones of cells located in the post-trochal region that also contribute to the shell gland/mantle (from both 2a 1, 2a 2 and 2c 1, 2c 2; Figs.",
"3h, k and 5i, q ).",
"On the other hand, 2a 1 and 2c 2 make some slightly different contributions.",
"Though both of these cells make contributions to the posterior, dorsolateral clones of cells located in the post-trochal region (Figs.",
"3h, m and 5i, s ), 2a 1 does not contribute to the mouth or esophagus (Fig.",
"3m ), while 2c 2 does (Fig.",
"5k ).",
"Fine speckles of labeled material are also seen mainly on the right anterior side of the head, which are derived from the progeny of 2c (Fig.",
"5c – e, ,g, g, ,h h – l, ,o o – p ).",
"These appear to be too small to be cells, and their identity is uncertain (see also [ 18 ]).",
"Hejnol et al.",
"[ 31] reported that ectoderm covering the left external kidney (absorptive cell) was derived from 2a; however, Lyons et al.",
"[ 34] showed that this structure is derived from 4d and is directly exposed to the external environment.",
"Hejnol et al.",
"[ 31] also reported that some ectomesoderm is also derived from 2c.",
"Specifically, they reported that the ectodermal covering of the larval heart and muscles of the heart are derived from 2c.",
"Here, we find no evidence of any ectomesoderm being derived from 2c (Fig.",
"15 ).",
"In fact, recently, we showed that the heart muscles are actually derived as endomesoderm from 4d [ 34 ].",
"Hejnol et al.",
"[ 31] reported that 2a and 2c give rise to the left and right coverings of the statocysts, respectively, and to the pedal and apical ganglia, as well as the osphradium (the latter being derived from 2c, which we have not verified here).",
"The second quartet (2b)Initially, 2b gives rise to a clone of ectodermal cells located along the very anterior edge of the blastopore (Figs.",
"4a and and14).",
"14 ).",
"This clone gives rise to two wings, and later gives rise to bands that extend bilaterally to the sides of the embryo (Fig.",
"4a – j ).",
"The right and left bands of cells are derived mainly from 2b 1 and 2b 2, respectively.",
"A single ciliated cell derived from 2b 2 lies at the ventral midline at the very anterior (top) opening of the mouth (Fig.",
"4o – s ).",
"An isolated group of 2–3 small rounded cells derived from 2b 1 also lie in the head anterior to the mouth (Fig.",
"4o – p, ,u u – w ).",
"These cells presumably give rise to neural cells or may undergo cell death, as they become hard to identify in older embryos.",
"2b gives rise to ectoderm located anterior to the mouth.",
"The bilaterally symmetrical bands of cells derived from 2b 1 and 2b 2 give rise to the ciliated food grooves (see also [ 31 ]), as well as some nerves in the head (Figs.",
"4q – y and and15).",
"15 ).",
"As these bilateral bands extend further to the dorsal side, (Fig.",
"4k, ,l), l ), they eventually fuse along the dorsal midline (Fig.",
"4m, ,n).",
"n ).",
"Here, two large cells each derived from 2b 1 and 2b 2 detach from their sister cells and move posteriorly along the dorsal surface to give rise to part of the shell gland and mantle.",
"As this occurs, those former cells appear to become depressed below the surface within the ectoderm compared to the surrounding cells.",
"The bands of cells derived from 2b 1 and 2b 2 also expand to contribute to dorsal-lateral ectoderm adjacent to the head bulge (head vesicle, which is derived from the first quartet micromeres, not followed here).",
"The dorsal-right lateral clone derived mainly from 2b 1 expands to a greater extent, compared to that on the dorsal-left side (mainly from 2b 2, Fig.",
"4t vs. vs.u u ).",
"The second quartet (2d)The ectodermal progeny of 2d originally lie along the very posterior edge of the blastopore (Figs.",
"6a–b and and14), 14 ), but this is the only clone of second quartet cells that is eventually excluded from the blastopore lip and does not contribute to either the esophagus or the mouth (Figs.",
"6b–p and and15).",
"15 ).",
"These cells are pushed away from the lip when clones derived from 3c and 3d, specifically 3c 2 and 3d 2, fuse along the ventral midline at approximately 97 hpf (Figs.",
"6j, ,10, 10,,11, 11, ,12, 12, and and14).",
"14 ).",
"That behavior is described in greater detail below.",
"2d 1 and 2d 2 give rise to nearly bilaterally symmetrical clones of posterior ectoderm (Fig.",
"6l – m, ,q q – s ).",
"Both of these cells give rise to much of the post-trochal ectoderm and both contribute also to the formation of the shell gland and the mantle (Figs.",
"6t – dd and and14).",
"14 ).",
"There are two unlabeled voids inside the posterior clone of labeled 2d cells that represent the two “terminal cells” derived from 3c 2 and 3d 2, respectively (Figs.",
"(Figs.6q 6q and 13b; see further discussion below).",
"As cells derived from 3c 2 and 3d 2 extend posteriorly into these clones (together with cells derived from 3c 1 and 3d 1 ), they cleave them to form two “V” shaped arms, one each derived from 2d 1 and 2d 2, respectively (Fig.",
"6q – s ).",
"These two arms each contain three cells that ultimately form bilateral, neuro-sensory structures located in the foot (Fig.",
"6v – dd; see description by [ 31 ]).",
"2d also gives rise to prominent neurons that extend from the post-trochal region to those neuro-sensory cells that become located in the tip of the foot, as well as to the apical organ in the head.",
"A prominent pair of bilateral ganglia are located on the left and right sides of the post-trochal region from which these axons extend (Fig.",
"6bb, ,cc).",
"cc ).",
"The tip of the developing hindgut intestine is located directly under posterior ectoderm derived from 2d (Figs.",
"6 and 13a – j ).",
"Often, there is a fluorescently brighter patch of labeled ectoderm directly over the terminal end of the hindgut that is derived from 2d 2 (Fig.",
"13b, ,d, d, ,f f – g ).",
"As asymmetric rotation of the visceral mass takes place, this patch of ectoderm follows the posterior end of the digestive tract and moves up the right side of the developing veliger larva (Fig.",
"13a – c, ,h h – j ).",
"The proctodeum or anus opens within this 2d 2 derived ectoderm later in development at approximately 12 days of development (Figs.",
"13h – j and and15 15 ).",
"The third quartet (3a and 3b)All four of the third quartet micromeres generate cells located along the lip of the blastopore (Figs.",
"3, ,4, 4, ,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, ,13, 13, and and14).",
"14 ).",
"Together, these contribute to most of the circumference of the blastopore.",
"3a and 3b give rise to bilaterally symmetrical clones that reside on the left and right sides of the embryo, respectively, which are situated closer to the future anterior pole (Figs.",
"7b – f and and8b 8b – e ).",
"Their vegetal most progeny, derived from 3a 2 and 3b 2 are the ones that initially lie along the anterior-lateral rim of the blastopore (Fig.",
"14 ).",
"These cells ultimately dive deep during gastrulation and form the ectomesoderm (Figs.",
"7h – o, ,8f, 8f, ,h h – k,,m, m, ,n, n, and are described in greater detail below, and Fig.",
"9 ).",
"As this happens, the animal progeny derived from 3a 1 and 3b 1, in turn take their place along the rim of the blastopore lip/blastopore boundary and contribute to the development of the esophagus and the mouth (Figs.",
"7j, ,k k and and8l).",
"8l ).",
"Cells arrayed in short straight bands extend to the left and right sides of the 3a 1 and 3b 1 clones away from the blastopore/mouth (Figs.",
"7h – p and and8g 8g – j, ,l).",
"l ).",
"These arms extend only as far as the lateral edges of the embryo.",
"These clones contribute to the food groove and metatroch and post-trochal (post-oral) velar ectoderm in the vicinity of the mouth and the foot (Figs.",
"7o, ,p p and and8n, 8n, ,o o ).",
"Formation and behavior of ectomesoderm (3a 2and 3b 2)The lineage analyses described above revealed that ectomesoderm arises from the 3a 2and 3b 2 micromeres.",
"These cells initially divide twice to form a line of four cells located along the anterior-lateral edges of the blastopore, at the boundary with the blastopore lip (Figs.",
"9a – i, ,14, 14, 16a ).",
"Ultimately, these cells undergo further proliferation to give rise to a larger number of mesenchymal cells (Figs.",
"7, ,8, 8, and and9j 9j – u ).",
"As gastrulation takes place, these cells roll into the blastopore to occupy deeper positions (Fig.",
"9s – u; Additional files 6 and 7 ).",
"As this begins to take place, the anterior blastopore narrows (Figs.",
"2 and and8f), 8f ), and these cells appear to loosen contacts with neighboring cells and become more rounded (Fig.",
"9t, ,u).",
"u ).",
"Eventually, they are covered by cells derived from their sister clones (3a 1 and 3b 1 ), which are part of the ectodermal lip of the blastopore (Figs.",
"9t, ,u u and and14).",
"14 ).",
"The 3a 2 and 3b 2 progeny are internalized by a process of ingression and ultimately undergo epithelial-mesenchymal transition (EMT).",
"They begin to migrate to remote locations within the embryo and larva beginning around 142 hpf (Fig.",
"9v–z; Additional file 8 ).",
"Some of the progeny derived from the left 3a 2 and right 3b 2 micromeres cross the ventral midline during their migration (Figs.",
"7j, ,n n and and8i).",
"8i ).",
"These cells form various fates, including velar muscles, muscles of the foot, as well as some fibers in the main retractor muscles, the latter being derived primarily from 4d (see [ 31 ]).",
"The third quartet (3c and 3d)3c and 3d give rise to bilaterally symmetrical (right and left) clones located along the posterior lip of the blastopore (Figs.",
"10, ,11, 11, ,12, 12, and and14).",
"14 ).",
"These cells contribute to the mouth, esophagus, foot, and post-trochal region (Fig.",
"15 ).",
"The vegetal progeny, derived from 3c 2 and 3d 2, initially lie along the rim of the blastopore lip (Figs.",
"10d, 11d, and 12a, ,s).",
"s ).",
"These cells each give rise to four progeny that form a single line of cells along the lip that do not divide further (Figs.",
"12 and and14).",
"14 ).",
"The medial ends of these two lines of cells are initially separated from one another by cells derived from 2d 1 and 2d 2 (Figs.",
"6, ,14 14 and and16).",
"16 ).",
"Subsequently, 3c 2 and 3d 2 progeny move toward the ventral midline by a process of convergence and extension, and undergo intercalation, which is described in greater detail in the next section (Fig.",
"12 ).",
"These cells all become multi-ciliated and form a group of cells that extends along the ventral midline, from the posterior esophagus and mouth, to the posterior end of the embryo (Fig.",
"12dd, ,ee ee ).",
"The much larger group of cells derived from 3c 1and 3d 1contribute mainly to the left and right halves of the foot and to the statocysts (Figs.",
"10m–t, 11m, ,p p – x, and and15).",
"15 ).",
"In addition, these cells give rise to thin bands that lie within the post-trochal ectoderm on the posterior surface of the right and left velar lobes (Figs.",
"10p – r, 11n – u, and 13k – o ).",
"Hejnol et al.",
"[ 31] indicated that 3c and 3d give rise to the left and right external larval kidneys, but Lyons et al.",
"[ 34] showed that both the left and right external larval kidneys (absorptive cells) are derived from 4d.",
"The posterior blastopore lip: closure by convergence and extension At flattened round stages, the posterior/lateral lip of the blastopore is made up of two lines of four cells each derived from the vegetal-most daughters of the 3c and 3d (i.e., 3c 2 and 3d 2; Fig.",
"12a, s ).",
"Initially, derivatives of 2d 1 and 2d 2 cells lie between these 3c 2 and 3d 2 cells at the lip (Figs.",
"6j, 12v, x, ,z, z, and and14).",
"14 ).",
"At approximately 97 hpf, 2d 1 and 2d 2 are pushed away from the posterior lip when the 3c 2 and 3d 2 progeny subsequently interdigitate by zippering along the ventral midline (Figs.",
"12a–u and and14; 14; Additional file 9 ).",
"This zippering is accomplished by a novel form of convergence and extension.",
"A consequence of this zippering process is that the posterior blastopore lip closes, narrowing the blastopore.",
"Beginning at the time, these cells undergo zippering; they all become multi-ciliated (Fig.",
"12 12bb bb – mm; Additional file 10 ).",
"Each of these four 3c 2 and 3d 2 progeny extend a long thin filopodial process along the edge of the blastopore lip that forms contacts at the posterior ventral midline (Fig.",
"12m–o ).",
"Those cells subsequently converge along the ventral midline to form two columns of cells that undergo intercalation and extension.",
"The four originally medial cells (3c 221, 3c 222, 3d 221, 3d 222) are displaced posteriorly and removed from the blastopore lip (Figs.",
"10f–j and 11e–j ).",
"The four originally more lateral cells (3c 211, 3c 212, 3d 211, 3d 212) contribute to the mouth and esophagus (Figs.",
"10o–t, 11m–y, and and15), 15 ), where the two most lateral cells end up diving deep into the archenteron to contribute to the esophagus (3c 211, 3d 211; Figs.",
"10i–o, 11m, and 12s – ll ).",
"Those next to them contribute to the posterior mouth (3c 212, 3d 212 ).",
"The other cells form a line that extends along the ventral midline.",
"Two of these lie just posterior to the opening of the mouth (3c 222, 3d 222 ).",
"The two cells (3c 221, 3d 221) that were initially the most medial cells prior to zippering give rise to the bilateral right and left “anal” cells, respectively, which were described by Conklin [ 42 ].",
"Despite their name, these two cells do not contribute to the proctodeum and to avoid further confusion we have renamed them “terminal cells” (Fig.",
"15; [ 43 ]; see discussion ).",
"As the 3c 2/3d 2-derived cells zipper, they displace 2d progeny further away from the blastopore lip and towards the posterior pole of the embryo.",
"They extend into the clone of cells derived from 2d, so that after zippering has finished, two elongated V shaped left and right columns of cells extend from the main 2d clone (the right arm from 2d 2 and the left arm from 2d 1; Figs.",
"6q – s, 12z – aa, and and14).",
"14 ).",
"The terminal cells initially lie within the clone of 2d ectoderm that sits over the terminal end of the hindgut (Figs.",
"10p – t and 11r – y ).",
"Subsequently, the terminal cells are displaced further from the end of the hindgut (Fig.",
"13k – s ).",
"Go to: Discussion Early epiboly: expansion of the micromere cap Gastrulation occurs by diverse mechanisms among spiralians [ 10 ].",
"Epiboly is common to many species with yolk-rich eggs, including Crepidula [ 10, 42 ].",
"Though there are gross morphological descriptions of this process, very few specifically focus on the behavior of individual cell lineages [ 16, 18 ].",
"Here, we traced the lineages of the second and third quartet micromeres to specific germ layers, and to openings of the digestive tract (Figs.",
"1, ,14, 14, and and15 15 ).",
"In Crepidula, epiboly occurs as cells of the micromere cap proliferate and flatten to cover endodermal and mesodermal precursors (Figs.",
"1 and and2).",
"2 ).",
"These events are similar to what was described for Helobdella [ 16] and for the flatworms Imogine mcgrathi and Maritigrella crozieri [ 44, 45 ].",
"However, a double layer of ectodermal cells does not form in Crepidula, as described in Maritigrella [ 44 ].",
"In Crepidula, cell divisions occur continuously during epiboly, throughout the epithelium, whereas in Helobdella, mitoses in the cap are largely restricted to early stages of epiboly, and cell division is rarely observed at the leading edge of the cap [ 16 ].",
"To cover the large, yolky macromeres, the micromere cap’s marginal circumference must first increase to reach the equator and then decrease as the cap narrows around the vegetal hemisphere of the embryo.",
"This latter step is accomplished in Helobdella, in part, by virtue of that fact that cells at the leading edge become wedge shaped, with their narrow edges at the lip.",
"This wedging behavior was not pronounced in Crepidula; however, we noticed extensive cell shape changes at the leading edge (Fig.",
"2 ).",
"These changes are discussed further below, for each of the second and third quartet micromeres, which make up the leading edge of the epithelial cap.",
"Origin and behavior of the ectomesoderm (progeny of 3a 2and 3b 2)Spiralians typically have two sources of mesoderm.",
"The first is endo mesoderm, derived from the 4d micromere, and gives rise to mesodermal derivatives such as adult muscle, heart, and excretory structures [ 34, 46 ].",
"Spiralian endomesoderm appears to be highly conserved with endomesoderm in other metazoans, both in terms of cell fates [ 34, 46] and gene expression [ 47, 19, 23 ].",
"The second is ecto mesoderm, which arises from various second and third quartet cells, depending on the species examined [ 10, 48 ].",
"Ectomesoderm gives rise to scattered mesenchyme, which can contribute to larval tissues such as the velar muscles in Crepidula [ 10, 31, 48, 49 ].",
"Ectomesoderm is likely a spiralian innovation, and the behavior and profile of genes expressed in these cells are not well understood [ 10, 50, 51 ].",
"An earlier study in Crepidula followed the contributions of embryonic cells later into larval development and reported that ectomesoderm arises from 3a, 3b, and 2c [ 31 ].",
"The origin of ectomesoderm from 3a and 3b is considered to be a plesiomorphic character among spiralians [ 10, 31 ].",
"In the present study, we observed no evidence of ectomesoderm arising from 2c (though this may arise at later stages of development).",
"We found that ectomesoderm arises more specifically from the 3a 2 and 3b 2 cells (Figs.",
"7 and and8 8 ).",
"The mechanisms of ectomesoderm internalization have not been investigated in detail, but internalization is generally assumed to occur by an epithelial to mesenchymal transition (EMT) [ 10 ].",
"We show that clones of cells derived from 3a 2 and 3b 2 occupy the anterior-lateral sides of the blastopore by ~94 hpf when the lip has just passed the equator of the embryo (Table 1; Figs.",
"9 and and14).",
"14 ).",
"Initially, these cells are rather large and flat, forming lines of stretched cells along the anterior-lateral rim of the blastopore.",
"Subsequently, these cells round up and proliferate (Fig.",
"9 ).",
"Their progeny remain well rounded (which may indicate that they have weaker adhesive properties) while they collectively sink into the archenteron (Figs.",
"7, ,8, 8, and and9).",
"9 ).",
"As this occurs, these cells are covered by trailing cells derived from 3a 1 and 3b 1.",
"Despite using various lineage tracers and fluorescently tagged biosensors for the actin cytoskeleton (utrophin-GFP), we did not observe any obvious signs of dynamic cell membrane protrusions (e.g., filopodia or lamellipodia), or evidence of apical constriction in these cells during the initial phase of their entering the archenteron.",
"Thus, the early behavior of these cells is distinct when compared to classic forms of EMT, such as in sea urchin primary mesenchyme ingression, where ingressing cells exit the cell cycle, extend filopodia, and slip out of the epithelium [ 52 ].",
"Only after they become covered by the surface ectoderm and move into the archenteron do these ectomesodermal cells extend filopodia and disperse, crawling to distant locations within the embryo (Fig.",
"9; Additional file 8 ).",
"Origin and formation of the mouth (second and third quartet)As ectomesoderm leaves the leading edge of the micromere cap, its circumference becomes reduced.",
"This removal of cells may help drive constriction of the blastopore lip along its anterior-lateral edges, as the blastopore takes on a narrowed, slit-like appearance (Fig.",
"2 ).",
"Likewise, other cells, derived from 2a, 2c and 3a–3d, also extend into the archenteron to form tissues of the foregut/esophagus, and this could also contribute to narrowing of the blastopore.",
"Despite Conklin’s [ 42] statement, the blastopore does not completely close in Crepidula, and gives rise to the mouth in a true protostome fashion (Fig.",
"14 ), just as was recently reported for Ilyanassa [ 18 ].",
"Previous descriptions by Conklin [ 42] and Hejnol et al.",
"[ 31] reported that the progeny of mainly the second quartet form the mouth in Crepidula, while third quartet progeny make the ectodermal esophagus (or foregut).",
"By tracing the exact locations of these cells throughout gastrulation, we found that contributions to the mouth and esophagus are more complicated.",
"The mouth is derived from 2a 2, 2b 2, 2c 1, 2c 2, 3a 1, 3b 1, 3c 1, 3c 2, 3d 1, and 3d 2, and all those except 2a 2 and 2b 2 also contribute to deeper tissues of the esophagus (Figs.",
"3, ,4, 4,,5, 5, ,6, 6, ,7, 7, ,8, 8, ,9, 9, ,10, 10, ,11, 11, ,12, 12, and and15).",
"15 ).",
"These contributions are similar to those noted for Ilyanassa [ 18 ], including the small contribution of the 2b lineage (2b 2) to the anterior-most part of the mouth.",
"Interestingly, the relative contribution of second versus third quartet lineages to the mouth and esophagus appears to vary across species (see discussions in [ 53] and [ 18 ]).",
"It could be that differential proliferation and cell re-arrangements during blastopore narrowing, along with different contributions of these cells to ectomesoderm, accounts for species-specific variation.",
"Convergence and extension of the posterior blastopore lip: “zippering” of 3c 2 and 3d 2 progeny By the time the blastopore lip has passed the equator, the posterior half of the blastopore lip is occupied by four cells derived from 3d 2 on the left and four cells from 3c 2 on the right (Figs.",
"1,,12, 12, ,14, 14, ,16).",
"16 ).",
"Between them, at the very posterior-most edge of the lip, lie two cells derived from 2d 1 and 2d 2.",
"Beginning at ~94 hpf, these two cells are excluded from the blastopore lip by convergence and extension that involves intercalation of some of the 3c 2 and 3d 2 descendants.",
"During this process, these cells extend thin processes that make contact with cells from the opposite sides.",
"This convergence begins with the most medial, posterior cells in each clone (3c 221, 3d 221 ), followed by more lateral, anterior cells, which is reminiscent of a closing zipper.",
"As these cells converge, they form a pair of columns along the anterior-posterior axis that undergo intercalation to form a more extended column of ciliated cells (Fig.",
"12dd, ,ee ee ).",
"This study presents the first description of blastopore lip morphogenesis using clonal analysis and live imaging.",
"Closure of the posterior blastopore has been described in other species (e.g., Platynereis [ 23 ], Hydroides, [ 17 ], Patella, [ 43 ]), but the specific cell behaviors involved were not investigated.",
"The behavior exhibited by Crepidula likely takes place in other spiralians.",
"Although Chan and Lambert [ 18] do not specifically remark on this phenomenon, their images of the 3c and 3d clones show that Ilyanassa likely develops in a similar fashion (their Fig.",
"4j, n ).",
"Among annelids, Woltereck’s [ 54] drawings of Polygordius, reveal a similar posterior-ventral “zig-zag” seam comprised of two columns of left and right cells, which might reflect a similar zippering behavior [ 7, 12, 54 ].",
"The process observed in Crepidula could also account for the arrangement of cells observed in the study of Lartillot et al.",
"[ 43 ], in the gastropod Patella (see their Fig.",
"5 ).",
"Those authors speculate that cells posterior to the blastopore elongate along the ventral midline by directed stem cell like divisions, but that was based solely on gene expression data and not on intracellular lineage tracing; it is possible that the elongation is instead the result of convergence and extension along with cell intercalation.",
"Convergent extension was recently reported in the annelid Platynereis [ 55 ]; however, that process is different, as it occurs within two separate populations of neuroectodermal precursors that lie to the sides of the ventral midline after blastopore closure has taken place.",
"Lineage tracing in each of these species would address how similar their gastrulation processes are to that found in Crepidula.",
"Ciliary bands: the food groove and the metatroch (second and third quartet)Hejnol et al.",
"[ 31] reported that the metatroch, a ciliated, reverse-current (downstream) feeding band, is derived from 2a and 2c, while the ciliated food groove, lying between the metatroch and the prototroch (derived from the first quartet micromeres), is derived from 2b (Fig.",
"4 ).",
"Here, we extend those results by showing that the food groove is derived from both 2b 1 and 2b 2, in addition to 3a 1 and 3b 1, and the metatroch is derived from 2a 2 and 2c 2, as well as 3a 1 and 3b 1.",
"The 3c 1 and 3d 1 clones also extend long thin bands of cells, but those are located on the posterior surface of the velum, behind the metatroch.",
"The differences between our studies may be related to the fact that Hejnol et al.",
"[ 31] examined fixed embryos, and we analyzed live material, which is much better for making fine assessments of cell lineage fates.",
"Gharbiah et al.",
"[ 56] reported in Ilyanassa that the metatroch arises from 3a–3d and 2a–2c, and the food groove is from 2a–2c, as well as 3a–3b.",
"These findings continue to support the argument that the homologization of these ciliated bands across large evolutionary distances is problematic [ 57 ].",
"The neurotroch (3c 222, 3c 222)Following the zippering of the posterior blastopore lip, the daughter cells from 3d 2and 3c 2each contribute to four sets of ciliated cells present in the posterior ventral ectoderm (Fig.",
"12 ).",
"These include two deeper cells in the esophagus (3c 211, 3d 211 ), two in the mouth (3c 212, 3d 212 ), two cells we believe could be analogous to a neurotroch (3c 222, 3d 222 ), and more posteriorly, two “terminal cells” that could be analogous to a telotroch (3c 221, 3d 221 ).",
"These cells all become ciliated during posterior blastopore closure (Fig.",
"12bb – mm ).",
"In some larvae of other spiralians, the neurotroch (also sometimes called the gastrotroch, but not to be confused with the ciliated bands on the segments of polychaetes; see [ 58 ]) represents a double row of multi-ciliated cells that runs along the ventral midline, posterior to the mouth and extends towards the anus [ 59 ].",
"The neurotroch has been argued to be a plesiomorphic feature of spiralian larvae [ 60 – 62 ].",
"Cilia of the neurotroch beat towards the anus, but the exact function of the neurotroch is uncertain.",
"This structure, which is present in some annelids and entoprocts, is apparently not found in platyhelminthes, nemerteans, rotifers, or molluscs [ 60, 62 ].",
"The neurotroch typically comes from the 2d lineage [ 29 ].",
"For example, in Capitella, the neurotroch is made up primarily of 2d cells, with 3c and 3d also contributing a small number of anterior cells [ 53 ].",
"In Ilyanassa, there are a few ciliated cells in the foot [ 56] derived from 3c and 3d [ 18 ].",
"We argue that the 3c 222 and 3d 222 cells of Crepidula could be analogous, or even homologous, to the neurotroch in other spiralians.",
"The telotroch (3c 221and 3d 221)The telotroch (sometimes referred to as paratroch) represents a posterior ciliated band that encircles the anus and is believed to have a function in locomotion [ 63 ].",
"Telotrochs have been found in many annelids (including echiurans and sipunculids) and some molluscs, including the gastropod Patella [ 53, 64 – 66 ].",
"Its presence has also been reported for aplacophorans (e.g., Neominiomorpha and Chaetodermorpha ), and given their basal position in the Mollusca, this structure is regarded as a plesiomorphic condition for that phylum [ 60, 67 ].",
"A telotroch has also been reported for the pilidium larva of one nemertean [ 68, 69 ], though this is likely a derived structure.",
"Nielsen [ 60] argues that the telotroch is a feature of the ancestral trochophore larva, though Strathmann [ 63] suggests this structure could have evolved on multiple occasions, and Rouse [ 67] argues that only the prototroch is ancestral for the Trochozoa.",
"The telotroch is said to be derived from 2d in the annelids Arenicola [ 70] and Amphitrite ( [ 29, 71 ]).",
"The telotroch in the polychaete annelid Capitella is also derived from 2d [ 53, 65 ].",
"In the gastropod Patella, the telotroch is mainly derived from 2d, but includes two distinctive anterior ciliated cells derived from 3c and 3d [ 64 ].",
"We argue that the two posterior ciliated cells in Crepidula (3c 221 and 3d 221) are homologous to those two telotroch cells.",
"These represent the posterior-most cells in the Crepidula embryo following posterior blastopore lip closure (Fig.",
"12s–u ).",
"They are surrounded by ectoderm derived from 2d, and they are the only ciliated cells in this region (Figs.",
"6q, x and 12ff, ,gg).",
"gg ).",
"These cells represent what Conklin [ 42] and others referred to as “anal cells,” as they assumed that they contributed to the proctodeum.",
"We show clearly that these cells do not make the anus, which arises instead from the 2d lineage (2d 2, see below).",
"Thus, we deemed it necessary to re-name these cells, and propose calling them “terminal cells”; the term used for what we assume to be the homologous cells in Patella [ 43 ].",
"Lartillot et al.",
"[ 43] stated that terminal cells arise from the 3c 11 and 3d 11, and that these cells give rise to the anus, but there is no published lineage data to support those claims.",
"Origin and formation of the anus (2d 2)There are various reports regarding the origins of the ectodermal anus (proctodeum) in spiralians [ 10, 53 ].",
"In the classical literature, for instance, Treadwell [ 72] argued that cells derived from 3c give rise to part of the proctodeum in Podarke, but Nielsen [ 29] suggests that this is not well demonstrated.",
"The anus was said to be derived from 2d in the annelids Arenicola [ 70] and Amphitrite (Nielsen [ 29 ]).",
"More recently, intracellular lineage tracing in Capitella [ 53] showed that the ectodermal anus is derived from 4d, which appears to be a unique situation.",
"As mentioned above, earlier investigators referred to ciliated “anal cells”, which were thought to give rise to the anus (e.g., [ 42, 73 ]).",
"We show in Crepidula that these terminal cells (derived from 3c 221 and 3d 221) are located near the end of the hindgut early during development, but they become displaced from this location at later stages (Fig.",
"13k–s ).",
"Instead, our current study demonstrates that the anus is derived from the 2d 2 clone, which forms ectoderm lying directly over the termination of the hindgut (Fig.",
"13a–j ).",
"In Capitella, the 2d clone also surrounds the 4d-derived anus, and the 3c and 3d micromeres contribute cells to this area as well, but are subsurface, as 3c and 3d progeny are ectomesodermal in this species [ 53 ].",
"In a previous study [ 34 ], we observed that the anus did not form when specific progeny of 4d were ablated (e.g., 3m L/R), which contributes largely to the formation of the terminal endoderm of the hindgut.",
"These data suggested that inductive interactions may be required to induce the formation of the proctodeum.",
"It is possible, however, that we did not follow those larvae long enough to fully determine if the anus could form or not.",
"Its development could have also been delayed in those experimental cases.",
"In the course of this study, we found that the opening of the anus does not appear until 12 days after fertilization.",
"On the other hand, the location of the anus may indeed require inductive interactions from the hindgut, as suggested by those earlier experiments.",
"When performing the lineage analyses here, we noticed that the hindgut becomes distended or swollen before the anus opens (Fig.",
"13j ).",
"At that point, the intestine collapses down to a narrow tube and cylindrical waist products begin to be expelled.",
"In some of the injected cases, there was no lineage tracer observed, which resulted from the accidental death of those injected 2d cells (data not shown).",
"In those same cases, the anus does not appear to open and the hindgut remains swollen, even though ectoderm covers the terminal end of the intestine.",
"These findings suggest that only the progeny of 2d may form the anus, and that these may be the only cells competent to respond to inductive interactions from the terminal hindgut endoderm.",
"It is possible that differences in the spatial relationships and inductive interactions between the hindgut (endodermal) terminus and the overlying ectoderm could account for species-specific variations in those cells that have been reported to give rise to the anus.",
"Differences between Crepidula blastopore morphogenesis and amphistomy The relationship between the blastopore and the mouth and anus is under debate [ 2, 5, 7, 8, 10, 22, 23 ].",
"The fact that there is variation in the site and behavior of the blastopore takes on particular evolutionary significance because the blastopore is developmentally related both to the blind gut of bilaterian out groups, like cnidarians, and to the through-gut of bilaterians.",
"Thus, it is reasoned that diverse bilaterian body-plans are related to, or even dependent on, changes to the site or behavior of the blastopore.",
"How did these changes come about?",
"According to one set of hypotheses, the bilaterian ancestor exhibited amphistomy, where a slit-like blastopore gave rise to both mouth and anus [ 3, 5 ].",
"According to this theory, protostomy and deuterostomy evolved from amphistomy as openings were retained at only the anterior or posterior end of the blastopore.",
"An alternative scenario argues that deuterostomy is ancestral among bilaterians, including ecdysozoans and spiralians/lophotrochozoans, and thus protostomy arose independently on multiple occasions as a modification of deuterostomy [ 6 ].",
"Thinking even more broadly, it has even been called into question if there are technically any prostostomes among the bilaterians, because the blastopore forms at the posterior pole in the Spiralia, but the mouth forms in the anterior ventral ectoderm from cells that were born near the animal pole [ 2, 13 ].",
"The detailed cell lineage studies that are necessary to distinguish between these hypotheses are often lacking within the spiralian/lophotrochozoan branch.",
"Very few examples of amphistomy, or deuterostomy, are reported among species with spiral cleavage, and no lineage tracing study has definitively documented either phenomenon [ 7, 10 ].",
"Despite the lack of strong evidence, the gastrulation behaviors of several species have been called upon to support the existence of amphistomy, or the remnants of an amphistomous ancestor.",
"For example, some point to Woltereck’s description of a slit-like blastopore in the annelid Polygordius as an extant example of amphistomy [ 5, 8, 54 ].",
"Yet, others disagree with this interpretation, pointing out that Woltereck himself stated, and illustrated, that the posterior portion of the blastopore closes, while the anus arises from 2d-derived cells in a more posterior location [ 7, 12 ], which is similar to what we observed in Crepidula.",
"The behavior of extant species has been taken as evidence of a transition from amphistomy to protostomy.",
"The development of Patella [ 43 ], Hydroides [ 17 ], and Platynereis [ 23] has been interpreted in this way because the blastopore is said to seal up along the posterior ventral midline.",
"The zippering phenomenon that we observed in Crepidula might be homologous to the gastrulation processes in these other spiralian species.",
"However, no lineage tracing has correlated the position of clones around the blastopore with the formation of the mouth or anus in these species.",
"By emphasizing the behavior of the blastopore lip cells, and defining them as those cells that surround the endoderm/mesoderm in Crepidula (Fig.",
"16 ), we hope to establish a basis of comparison with other species.",
"Central to the definition of amphistomy are the notions that in the amphistomous ancestor: 1) the lateral edges of the blastopore fused, which 2) left persistent anterior and posterior holes, that 3) resulted in the simultaneous formation of the openings that became those of the mouth and anus, respectively.",
"However, the behavior of the Crepidula blastopore deviates from these definitions in several respects.",
"First, zippering of the posterior blastopore lip occurs in a posterior to anterior direction, rather than initiating at the lateral edges of the lip.",
"Second, only one hole persists after gastrulation and this becomes the mouth.",
"Third, it is not just the anterior portion of the blastopore lip that gives rise to the mouth, but clones from anterior, lateral, and posterior positions (Fig.",
"16 ).",
"Fourth, the mouth also forms from anterior, lateral, and posterior cells that were never part of the blastopore lip (Figs.",
"14, ,15, 15, and and16).",
"16 ).",
"Fifth, the anus arises as a separate hole from the blastopore, days after gastrulation has finished.",
"Some might view the behavior of cells at the posterior blastopore lip in Crepidula as an example of the proposed transition from amphistomy to protostomy (see [ 3, 5 ]), At the beginning of gastrulation (~90 hpf, Fig.",
"1d; Fig.",
"14, second row; Fig.",
"16a ), each of second and third quartet micromere lineages contribute progeny to the lip, including cells that give rise to the mouth (2a–2c, 3a–3d) and much later, to the anus (2d).",
"In this context, one could claim that cells of the early blastopore lip include progenitors that form both the mouth and the anus.",
"We note, however, that the progenitor cells that give rise to the anus are part of the blastopore lip for only a short duration, before being quickly excluded by the zippering of the 3c 2 and 3d 2 clones.",
"Furthermore, during the time the 2d clone is part of the blastopore lip, the anus has not yet formed.",
"Finally, we note that we have chosen to define the blastopore lip at a very early time in development (Fig.",
"16a ), by virtue of the fact that the ectodermal micromere cap internalizes the macromeres from the very beginning of epiboly.",
"If however, we took a more conservative approach and said that the blastopore lip does not form until later, when an obvious depression/archenteron forms (Fig.",
"16b, c ), then the 2d clone would not be present at the blastopore lip.",
"The definition of when the blastopore/blastopore lip forms is somewhat subjective and might vary species to species.",
"These semantic debates reflect how difficult it can be to make direct comparisons when talking about distantly related animals whose gastrulation processes are diverse; by making an explicit definition of the blastopore lip, we hope to make future comparisons with other animals more straightforward.",
"While we cannot exclude the possibility that Crepidula blastopore morphogenesis has been modified from an ancestral amphistomy condition, we note that no extant species has been shown to exhibit amphistomy, and classic examples of amphistomy have been called into question by many authorities [ 7, 11, 12 ].",
"Therefore, we argue that it is unlikely that protostomy is a modification of amphistomy.",
"If deuterostomy is ancestral to the bilaterians, as has been recently proposed (based on its widespread existence in extant deuterostomes and ecdysozoans [ 6, 11 ]), it will be of interest to understand the morphogenetic changes to cells around the blastopore that permitted such a transition.",
"We propose that it will be more useful to focus on homologizing cells at the blastopore lip (which can be lineage-traced, or assayed for expression of regulatory genes), than to focus on the blastopore hole itself.",
"Go to: Conclusions A morphogenetic perspective on the evolution of spiralian gastrulation Very little is understood about the underlying morphogenetic processes that occur during spiralian development.",
"Focusing on behaviors of specific lineages will be very informative for comparative studies.",
"Examining the cells that make the blastopore in different species is just one example.",
"We mention a few additional examples below.",
"We found that the 3q 2cells exhibit highly dynamic behaviors in Crepidula.",
"Cells derived from 3a 2 and 3b 2 undergo EMT during formation of the ectomesoderm, and the 3c 2 and 3d 2 cells undergo convergence and extension to close the posterior blastopore lip.",
"These cells display other interesting differences: the 3a 2 /3b 2 cells divide multiple times (giving rise to dozens of cells each), never become ciliated, and only form filopodia after they have become mesenchymal.",
"Conversely, the 3c 2 /3d 2 cells divide only twice (giving rise to just four cells each), become multi-ciliated, and form filopodia while still remaining in the ectoderm.",
"How these third quartet cells acquire their unique identities will be an interesting area of future research.",
"In Ilyanassa, inheritance of m RNA can distinguish different tiers of micromeres along the animal vegetal axis [ 74] while differential stability of m RNAs along the anterior-posterior/dorsal ventral axis can then distinguish different quadrants [ 50 ].",
"For example, the Tis11 transcript is initially inherited by all 3q micromeres, but is retained in only the 3a and 3b cells, which form ectomesoderm [ 18, 50 ].",
"In other species, like Platynereis and Capitella, the 3c and 3d cells contribute to ectomesoderm, and it would be interesting to compare cellular and molecular events within these different tiers and quartets of micromeres to understand the basis of this inter-species variation.",
"Another fruitful area of research would be comparing species that gastrulate by epiboly, emboly, and invagination [ 10 ].",
"For example, in Crepidula, the blastopore lip has to narrow considerably to cover the large endodermal macromeres; the zippering behavior we observed in the posterior blastopore lip might be necessary to cover those cells.",
"During invagination, in contrast, the endodermal cells are smaller, and the ectodermal cells near them might behave differently.",
"Furthermore, it would be interesting to study how similar the movement of cells towards the ventral midline in Patella, Hydroides, and Platynereis are to that in Crepidula.",
"In Capitella, the blastopore has been described to close completely [ 19 ], which might be accomplished by a more extensive zippering behavior, or a completely distinct mechanism.",
"Studying the details of cell lineages and their behaviors will address how such variation arose.",
"Finally, spiralians are one of the only groups of metazoans where homology of body-plans can be compared at the levels of gene expression and cell lineage.",
"Comparison of gene expression patterns in the posterior and anterior blastopore lip has been used in arguments about amphistomy [ 23, 43, 75 ], but in the absence of detailed lineage tracing during gastrulation stages.",
"It has been proposed that the differences in gene expression for endomesodermal markers might be a reflection of different life history strategies [ 17 ], which also correlate with different modes of gastrulation [ 10 ].",
"To test this interesting hypothesis, it will be necessary to have both gene expression and fate map data for multiple species [ 76 ].",
"Our goal here is to provide a framework for comparative studies of morphogenesis, in the hope that Crepidula will provide a useful point of reference for similar studies in other species.",
"Go to: Acknowledgements The authors thank the community of the Marine Biological Laboratory and especially Drs.",
"Richard Behringer and Alejandro Sanchez Alvarado.",
"DCL thanks DR Mc Clay for his support.",
"We also thank Drs.",
"Ray Keller, Mark Martindale, Elaine Seaver, Marc Servetnick, and Jose Martín-Durán for helpful discussions, as well as three anonymous reviewers for comments that improved the manuscript.",
"This material is based upon work supported by the National Science Foundation under Grant No.",
"1121268 to JQH (JJH).",
"Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.",
"Go to: Abbreviations Hpf hours post-fertilization Q macromere quartetq micromere quartet EMT epithelial-to-mesenchymal transition Additional files Additional file 1: (3.8M, mov)Movie 1.mov (Figure S1).",
"Time lapse light sheet confocal images of an embryo expressing the microtubule-cytoskeleton bio-sensor EMTB-GFP ( green) and an RFP-membrane biosensor ( red ).",
"Corresponds to Figure 1s.",
"Additional file 2: (719K, mov)Movie 2.mov (Figure 2f).",
"Time-lapse movie of embryos expressing UTPH-GFP during early epiboly.",
"Corresponds to Figure 2f.",
"Additional file 3 (856K, mov)Movie 3.mov (Figure 2g).",
"Time-lapse movie of embryos expressing UTPH-GFP during later epiboly.",
"Corresponds to Figure 2g.",
"Additional file 4: (829K, mov)Movie 4.mov (Figure 2h).",
"Time-lapse movie of embryos expressing UTPH-GFP during elongation.",
"Corresponds to Figure 2h.",
"Additional file 5: (566K, mov)Movie 5.mov (Figure 2i).",
"Time-lapse movie of embryos expressing UTPH-GFP during mouth formation.",
"Corresponds to Figure 2i.",
"Additional file 6: (992K, mov)Movie 6.mov (Figure 9a).",
"Time-lapse movie of an embryo injected with utrophin-GFP (UTPH) to mark cell outlines ( green ), and histone H2B-RFP (H2B) to mark nuclei ( yellow ).",
"Ventral view.",
"Corresponds to Figure 9a–i.",
"Additional file 7: (1.6M, mov)Movie 7.mov (Figure 9j).",
"Time-lapse movie of an embryo injected with ensconsin-GFP (EMTB) to mark microtubules ( green ), and histone-RFP (H2B) to mark nuclei ( yellow ).",
"Ventral view.",
"Corresponds to Figure 9j–u.",
"Additional file 8: (1.2M, mov)Movie 8.mov (Figure 9v).",
"Spinning disk confocal time-lapse of an embryo expressing utrophin-GFP (UTPH) globally ( green ), and in which the 3b micromere was labeled with di I ( red ).",
"Ventral view.",
"Corresponds to Figure 9v–z.",
"Additional file 9: (3.6M, mov)Movie 9.mov (Figure 12b).",
"Time-lapse movie of an embryo undergoing convergence and extension to zipper the posterior blastopore closed.",
"The 3c cell was injected with dextran ( green) and the 3d cell was injected with di I ( red ).",
"Corresponds to Figure 12b–l.",
"Additional file 10: (111K, mov)Movie 10.mov (Figure 12w).",
"Confocal time-lapse movie of 3c 2cells injected with di I, showing the beating of cilia.",
"Corresponds to Figure 12w.",
"Additional file 11: (11M, tiff)Figure S1.",
"Early epiboly and position of clones at the blastopore lip.",
"a–h Cartoons of early embryo with second and third quartet micromeres colored, as indicated in key to the right.",
"a–c Animal pole views; d is a ventral/vegetal view; e–h are lateral views.",
"Black and white cartoons are modified from Conklin’s drawings [ 42 ].",
"i–r Images of embryos during late cleavage and early epiboly stages labeled with the actin cytoskeleton marker UTPH-GFP ( white) and histone H2B-RFP (red); in some panels, the 4d clone is labeled with di I (red).",
"AV animal pole view, VV ventral/vegetal pole view, LV lateral view.",
"The 4d clone can often be identified without direct labeling because the UTPH-GFP is preferentially expressed or stabilized in this clone (e.g.",
"as in l, m, q, r ).",
"Scale bar equals 50 μm.",
"s–w Time lapse light sheet confocal images of an embryo expressing the microtubule-cytoskeleton bio-sensor EMTB-GFP and an RFP-membrane biosensor (MEM-RFP).",
"Lateral view.",
"Many cells are seen to divide over the course of the time-lapse ( arrow mitotic spindle), but the micromere cap does not make a significant advance towards the vegetal pole during this period.",
"See also Additional file 1, which corresponds to panels s–w.",
"Additional file 12: (18M, tiff)Figure S2.",
"Narrowing of the blastopore during later epiboly, and formation of the mouth/stomodeum.",
"a–e Confocal images of living embryos expressing UTPH-GFP to mark the actin cytoskeleton, and histone H2B-RFP to mark the nuclei.",
"Ventral views are shown during mid epiboly ( a ), late epiboly ( b ), elongation ( c ), and mouth formation ( d–e ).",
"f–i Time-lapse movies of embryos expressing UTPH-GFP during epiboly and mouth formation.",
"VV ventral view.",
"Scale bar equals 50 μm.",
"See also Additional files 2, 3, 4, and 5, which correspond to panels f, g, h, and i.",
"Additional file 13: (12M, tiff)Figure S3.",
"Fates of micromere 2a, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos with dextran- and di I-labeled 2a, or 2a subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated.",
"Anterior is up in all cases.",
"a Ventral view during early epiboly.",
"Corresponding ventral-view images are shown in b-c, d-e, f-g during late epiboly with different combinations of fluorescence and/or DIC layers shown.",
"h Shows a dorsal view of the same embryo shown in f-g. i, j Ventral views of older elongating embryos.",
"k, l Corresponding right lateral views of an older embryo undergoing organogenesis.",
"m Left lateral view of an older embryo undergoing organogenesis.",
"n, o Corresponding left lateral view of an older embryo undergoing organogenesis.",
"bp blastopore, ft foot, hg hindgut rudiment, mt metatroch, pgc primordial germ cell, rtc right terminal cell, sg shell gland, st stomodeum/mouth.",
"Scale bar equals 50 μm.",
"Additional file 14: (19M, tiff)Figure S4.",
"Fates of micromere 2b, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 2b, or 2b subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated.",
"Anterior is up in all cases.",
"a Ventral view during an early stage of epiboly.",
"b Ventral view during a later stage of epiboly.",
"Corresponding ventral views are shown in c-d, e-f, g-h, i-j during epiboly with different combinations of fluorescence and/or DIC layers shown.",
"Corresponding dorsal images are shown in k-l, m-n during epiboly.",
"o–q Ventral views of older, elongated embryos.",
"r Oblique left-lateral view of the ventral surface of an older embryo.",
"Corresponding left-lateral images are depicted in s-t and x-y of older embryos undergoing organogenesis.",
"u Right lateral view of an older embryo undergoing organogenesis.",
"v, w Corresponding oblique left-lateral views of the ventral surface of an older embryo undergoing organogenesis.",
"fg food groove, nc neural cells.",
"Other labels are the same as those used in Fig.",
"3.",
"Scale bar equals 50 μm Additional file 15: (15M, tiff)Figure S5.",
"Fates of micromere 2c, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos with dextran and di I labeled 2c, or 2c subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated.",
"Anterior is up in all cases.",
"a, b Corresponding ventral and dorsal views of an embryo near the end of gastrulation with different combinations of fluorescence and/or DIC layers shown.",
"c, d Corresponding ventral views of an embryo near the end of gastrulation.",
"e, f Corresponding ventral views of a slightly older embryo at the end of gastrulation.",
"g, h Corresponding ventral views of an older elongating embryo.",
"i Dorsal view of an elongating embryo.",
"j Ventral surface view of an embryo at the onset of organogenesis.",
"k, l Corresponding right lateral views of an embryo at the onset of organogenesis.",
"m, n Corresponding right lateral views of an older embryo during organogenesis.",
"o, p Corresponding oblique dorsal view of an embryo during organogenesis.",
"Corresponding right-lateral views of embryos undergoing organogenesis are shown in q-r, s-t. tc terminal cells.",
"Other labels are the same as those used in Fig.",
"3.",
"Scale bar equals 50 μm.",
"Additional file 16: (18M, tiff)Figure S6.",
"Fates of micromere 2d, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 2d, or 2d subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated.",
"Animal pole is up in a, anterior is up in b–dd.",
"a Dorso-lateral view of an early epiboly-stage embryo.",
"Corresponding ventral views of embryos during epiboly are shown in b-c, d-e, f-g with different combinations of fluorescence and/or DIC layers shown.",
"h, i Corresponding dorsal views of same embryo shown in f, g. Corresponding ventral view images of successively older embryos undergoing epiboly are shown in j-k, l-m. n, o Shows corresponding dorsal views of an embryo at the same stage as that shown in l, m. p Ventral surface view of an elongated embryo.",
"q Ventral view of embryo undergoing elongation.",
"Note unlabeled voids where the two terminal cells (tc) from 3c 221 and 3d 221 reside.",
"r, s Corresponding ventral views of embryo undergoing elongation.",
"t, u Right-lateral views of older embryo at the onset of organogenesis.",
"v, w Corresponding left-lateral views of embryo at the onset of organogenesis.",
"x, y Ventral views of embryo undergoing elongation.",
"Unlabeled voids occupied by the two terminal cells ( tc) are also indicated in x.",
"Corresponding left-lateral ( z, aa) and right-lateral/oblique ( bb, cc) views of older embryos during organogenesis.",
"dd Shows a ventral view of an embryo during organogenesis.",
"pb polar body, ns neurosensory cell.",
"Other labels are the same as those used in Figs.",
"3 and and4.",
"4.",
"Scale bar equals 50 μm.",
"Additional file 17: (12M, tiff)Figure S7.",
"Fates of micromere 3a, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3a, or 3a subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated.",
"Animal pole is up in a. Anterior is up in b–o.",
"a Dorso-lateral view of an early epiboly-stage embryo.",
"b Ventral (vegetal) view of early epiboly-stage embryo.",
"c-d, e-f Show corresponding ventral views of early and mid epiboly-staged embryos, respectively, with different combinations of fluorescence and/or DIC layers shown.",
"g, h Corresponding ventral views of later stage embryos undergoing epiboly.",
"i Ventral view of an older, elongating embryo.",
"j, k Ventral views of two embryos just prior to the onset of organogenesis.",
"Note that for the original stack of confocal images shown as a projection in j, the 3a 1 and 3a 2 clones are spatially separated in the Z axis, making it possible to pseudocolor them separately, as labeled.",
"Corresponding ventral views of embryo just prior to the onset of organogenesis are shown in l, m, n, o Left-lateral view of an embryo during organogenesis.",
"cb ciliary band, ms mesenchyme.",
"Other labels are the same as those used in Figs.",
"3 and and6.",
"6.",
"Scale bar equals 50μm.",
"Additional file 18: (12M, tiff)Figure S8.",
"Fates of micromere 3b, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3b, or 3b subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for histone H2B-RFP (H2B) and/or the actin-binding domain of utrophin-GFP (UTPH) to visualize nuclei or cell outlines, respectively, where indicated.",
"Animal pole is up in a. Anterior is up in b–o.",
"a Lateral-dorsal view of an early epiboly-stage embryo.",
"b-c, d-e show corresponding ventral (vegetal) views of early epiboly-staged embryos with different combinations of fluorescence and/or DIC layers shown.",
"f Ventral view of embryo during later epiboly.",
"g, h Show ventral views of two stages of mesenchyme migration.",
"i Ventral view showing numerous mesenchyme cells.",
"j, k Corresponding right-lateral views of embryos during organogenesis.",
"l, m Ventral surface views.",
"n, o Corresponding right-lateral views of older embryos during organogenesis.",
"Labels are the same as those used in Figs.",
"3, ,6, 6, and and7.",
"7.",
"Scale bar equals 50 μm.",
"Additional file 19: (18M, tiff)Figure S9.",
"Behavior of ectomesoderm (3a 2, 3b 2).",
"a–i Time-lapse movie of an embryo injected with utrophin-GFP (UTPH) to mark cell outlines, and histone H2B-RFP (H2B) to mark nuclei, where indicated.",
"Ventral view.",
"bp blastopore.",
"Several unidentified (x) daughter cells of 3a 2, 3b 2 are marked, in colors, to show the orientation of cell division and position of ectomesodermal precursor cells during the narrowing of the anterior blastopore lip.",
"Scale bar in f equals 50 μm; scale bar in i equals 25 μm.",
"j–u Frames from a timelapse movie of an embryo injected with ensconsin-GFP (EMTB) to mark microtubules, and histone-RFP (H2B) to mark nuclei.",
"Ventral view.",
"Dashed white lines outline the 3b 2 clone.",
"Scale bar in u equals 30 μm.",
"v–z Spinning disk confocal frames from a time-lapse of an embryo expressing utrophin-GFP (UTPH) globally, and in which the 3b micromere was labeled with di I (red).",
"Ventral view.",
"Scale bar in z equals 50 μm.",
"See also Additional files 6, 7, and 8.",
"Additional file 20: (15M, tiff)Figure S10.",
"Fates of micromere 3c, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3c, or 3c subclones, as indicated.",
"Animal pole is up in a and b. Anterior is up in c–t.",
"a, b Dorso-lateral views of early epiboly-stage embryos.",
"c, d Ventral views of early epiboly-stage embryos.",
"Corresponding ventral views of late epiboly-stage embryos are shown in e-f, g-h, i-j at successive stages of development with different combinations of fluorescence and/or DIC layers shown.",
"k, l Corresponding ventral and posterior views of an elongating embryo.",
"m, n Ventral views of embryos during elongation.",
"Corresponding right-lateral views of embryos during organogenesis o-p, s-t.",
"Note green background fluorescence is higher in s, t. (Q-R) Corresponding oblique, ventro-lateral views of an embryo during organogenesis.",
"nt neurotroch, rtc right terminal cell, pvb posterior velar band.",
"All other labels are the same as those used in Figs.",
"3 and and6.",
"6.",
"Scale bar equals 50 μm.",
"Additional file 21: (19M, tiff)Figure S11.",
"Fates of micromere 3d, and its subclones, during gastrulation and organogenesis.",
"Images of live embryos, with dextran and di I-labeled 4d, 3d, or 3d subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion proteins for the actin-binding domain of utrophin-GFP (UTPH) and histone H2B-RFP to visualize nuclei or cell outlines, respectively, where indicated.",
"Animal pole is up in a and b. Anterior is up in c–y.",
"a, b Dorso-lateral views of early epiboly-stage embryos.",
"c, d Ventral views of early epiboly stage embryos.",
"e–j Ventral views of elongating embryos later during epiboly.",
"k, l Corresponding ventral views of an embryo during elongation with different combinations of fluorescence and/or DIC layers shown.",
"m Right-lateral higher magnification views of an elongating embryo with inserts showing some of the ventral ciliated cells (shallow confocal stacks centered at the ventral midline).",
"n, o Corresponding ventral views of embryos during organogenesis.",
"Corresponding left lateral views of embryos during organogenesis p-q, r-s, t-u.",
"Corresponding ventral views of early veliger stage embryos v-w, x-y.",
"ltc left terminal cell.",
"All other labels are the same as those used in Figs.",
"3, ,6, 6, and and10.",
"10.",
"Scale bar equals 50 μm for a–l and n–y.",
"Scale bar equals 25 μm for m and 20 μm for its inserts.",
"Additional file 22: (16M, tiff)Figure S12.",
"Behavior of posterior blastopore lip cells undergoing convergence and extension (3c 2, 3d 2 ).",
"a–aa Projected confocal Z slices of embryos injected with dextran or di I, into 3c, 3d or their subclones, as indicated.",
"a Ventral view of an embryo at epiboly stage.",
"b–u Frames from a time-lapse of the same embryo as shown in a. b–l Frames from a time-lapse movie of the same embryo undergoing convergence and extension to zipper the posterior blastopore ( bp) closed.",
"m–r Frames from the same movie showing membrane protrusions (arrows) and cilia (arrow heads) on the cells undergoing convergent extension (zippering).",
"s, t Frames from the same movie showing that the cells undergoing convergence and extension are from the 3c 2 and 3d 2 cells.",
"The asterisk (*) marks cells from the 3c 1 and 3d 1 clones that migrate anteriorly towards the ventral side of the stomodeum.",
"In u, the 3c 211 and 3d 211 cells have entered the deeper parts of the mouth an are out of view of the stack, indicated by dashed lines.",
"v–aa Live confocal images of post-zippering-stage embryos showing the movement of the 3c 221 and 3d 221 cells posteriorly, between cells of the 2d clone.",
"bb–mm Images of fixed embryos stained for acetylated tubulin (to mark cilia) and DAPI (to mark DNA).",
"bb, cc Shows ventral views ( vv) of embryos at the early stages of convergent extension and arrowheads point to cilia on cells at the posterior edge of the blastopore.",
"dd–ff Ventral views of embryos during elongation.",
"The ciliated left and right terminal cells ( ltc, rtc) are labeled.",
"gg Posterior view ( pv) of the same embryo shown in ff.",
"Scale bar in l and mm are equal to 50 μm; scale bar in v equals 20 μm.",
"See also Additional files 9 and 10.",
"Additional file 23: (15M, tiff)Figure S13.",
"Origin of the anus (2d 2).",
"Images of live embryos, with dextran and di I-labeled 4d, 3d, 3c, 2d, or 2d subclones, as indicated.",
"In some cases, the zygote was previously injected with m RNAs coding for fluorescent fusion protein for the actin-binding domain of utrophin-GFP (UTPH) to visualize cell outlines, where indicated.",
"Anterior is up in all cases.",
"a–c Corresponding ventral views of embryos during organogenesis with different combinations of fluorescence and/or DIC layers shown.",
"d, e Corresponding right-lateral (oblique-ventral) views of embryo during organogenesis.",
"f, g Corresponding higher magnification right-lateral views of the posterior end of an embryo during organogenesis.",
"h, i Corresponding ventral views of veliger stage embryo after the anus as opened.",
"j Ventral view of a veliger stage embryo just before the anus opens.",
"Note that the hindgut is somewhat swollen.",
"k, l Corresponding ventral views of pre-veliger stage embryos.",
"m, n Corresponding (oblique-ventral) left-lateral views of the pre-veliger stage embryos.",
"o Ventral view of early veliger.",
"p, q Corresponding (oblique-ventral) left-lateral views of an early veliger.",
"r, s Corresponding ventral views of an early veliger.",
"an anus, nc neural cell, ns neurosensory cell, rm right mantle, tcs terminal cells (called tc in Fig.",
"6 ).",
"All other labels are the same as those used in Figs.",
"3, ,4, 4,,10, 10, and and11.",
"11.",
"Scale bar equals 50 μm for a–e, h–s.",
"Scale bar equals 25 μm in f, g. Additional file 24: (19M, tiff)Figure S14.",
"Summary of second and third quartet clones.",
"Columns show clones, colored as labeled, and according to those shown in Figs.",
"1 and and15.",
"15.",
"Rows show time points as indicated at the far right.",
"Top row shows animal views; all other rows show ventral views.",
"The smaller, irregularly shaped, stippled cells of the 3a 2 and 3b 2 clones represent ecto-mesenchyme located below the ectoderm Additional file 25: (18M, tiff)Figure S15.",
"Lineage diagram of second and third quartet micromeres and third quartet macromeres.",
"Colors correspond to those given in Figs.",
"1 and and14 14.",
"Additional file 26: (13M, tiff)Figure S16.",
"Morphogenesis of the blastopore lip.",
"a–e Vegetal/ventral views during gastrulation with the future anterior at the top of the figure.",
"Time points are the same as those shown in rows 2–6 in Figs.",
"1 and and14: 14: a ~94 hpf, b ~99 hpf, c ~120–130 hpf, d ~130–137 hpf, e ~140–145hpf.",
"The coloring shows the relative clonal contributions of cells within the embryo and to the blastopore lip.",
"The blastopore lip is marked in each panel by a solid white line.",
"The blastopore lip marks the boundary between the ectodermal micromere cap and the endoderm/endomesoderm/ectomesoderm.",
"As gastrulation proceeds, some cells leave the blastopore lip, but remain on the surface, and these are marked by a dashed white line.",
"The 2d cells are marked by a dashed yellow line in a, b, but are more difficult to follow in time points c–e and thus are not shown.",
"The 3c 2 - and 3d 2 -derived terminal cells (TC) are marked with an asterisk to follow their migration after they leave the blastopore lip.",
"Some cells of the blastopore lip move internally into the blastocoel/archenteron, and the solid white line can no longer be seen in some areas d, e. bp blastopore, em ectomesoderm (derived from 3a 2 and 3b 2 ).",
"Go to: Footnotes Competing interests The authors declare that they have no competing interests.",
"Authors’ contributions DCL and JQH designed and executed experiments, prepared figures, and co-wrote the first draft of the manuscript.",
"KJP executed experiments and prepared figures.",
"All authors contributed to revisions of the manuscript.",
"All authors read and approved the final manuscript.",
"Go to: Contributor Information Deirdre C. Lyons, Email: [email protected].",
"Kimberly J. Perry, Email: ude.sionilli@1rednajk.",
"Jonathan Q. Henry, Email: ude.sionilli@4yrneh-j.",
"Go to: References1.",
"Stern CD.",
"Gastrulation: from cells to embryo, Cold Spring Harbor Laboratory Press.",
"1 2004.2.",
"Martindale MQ, Hejnol A.",
"A developmental perspective: changes in the position of the blastopore during bilaterian evolution.",
"Dev Cell.",
"2009; 17 :162–74.",
"doi: 10.1016/j.devcel.2009.07.024.",
"[ Pub Med] [ Cross Ref]3.",
"Nielsen C. How to make a protostome.",
"Invertebr Syst.",
"2012; 26 :25. doi: 10.1071/IS11041.",
"[ Cross Ref]4.",
"Satoh N, Tagawa K, Takahashi H. How was the notochord born?",
"Evol Dev.",
"2012; 14 :56–75.",
"doi: 10.1111/j.1525-142X.2011.00522.x.",
"[ Pub Med] [ Cross Ref]5.",
"Arendt D, Nübler-Jung K. Dorsal or ventral: similarities in fate maps and gastrulation patterns in annelids, arthropods and chordates.",
"Mech Dev.",
"1997; 61 :7–21.",
"doi: 10.1016/S0925-4773 (96)00620-X.",
"[ Pub Med] [ Cross Ref]6.",
"Martín-Durán JM, Janssen R, Wennberg S, Budd GE, Hejnol A. Deuterostomic development in the protostome Priapulus caudatus.",
"Curr Biol.",
"2012; 22 :2161–6.",
"doi: 10.1016/j.cub.2012.09.037.",
"[ Pub Med] [ Cross Ref]7.",
"Hejnol A, Martindale MQ.",
"Mouth, the anus, and the blastopore—open questions about questionable openings - Oxford Scholarship.",
"In: Telford MJ, Littlewood DTJ, editors.",
"Anim Evol Genomes, Foss Trees.",
"Oxford: Oxford University Press; 2009. pp.",
"33–40.8.",
"Arendt D. Comparative aspects of gastrulation.",
"In: Stern CD, editor.",
"Gastrulation from cells to embryo.",
"New York, NY: Cold Spring Harbor Laboratory Press; 2004.9.",
"Chea HK, Wright CV, Swalla BJ.",
"Nodal signaling and the evolution of deuterostome gastrulation.",
"Dev Dyn.",
"2005; 234 :269–78.",
"doi: 10.1002/dvdy.20549.",
"[ Pub Med] [ Cross Ref]10.",
"Lyons DC, Henry JQ: Ins and outs of spiralian gastrulation.",
"Int J Dev Biol 2014, 58:413-28.",
"[ Pub Med]11.",
"Janssen R, Jörgensen M, Lagebro L, Budd GE.",
"Fate and nature of the onychophoran mouth-anus furrow and its contribution to the blastopore.",
"Proc Biol Sci.",
"2015;282.",
"[ PMC free article] [ Pub Med]12.",
"Van den Biggelaar JAM, Edsinger-Gonzales E, Schram FR: The improbability of dorso-ventral axis inversion during animal evolution as presumed by Geoffroy Saint Hilaire.",
"Contrib to Zool 2002, 71: http://www.ctoz.nl/vol71/nr01/a03.13.",
"Martindale MQ.",
"Evolution of development: the details are in the entrails.",
"Curr Biol.",
"2013; 23 : R25–8.",
"doi: 10.1016/j.cub.2012.11.023.",
"[ PMC free article] [ Pub Med] [ Cross Ref]14.",
"Hejnol A.",
"A twist in time–the evolution of spiral cleavage in the light of animal phylogeny.",
"Integr Comp Biol.",
"2010; 50 :695–706.",
"doi: 10.1093/icb/icq103.",
"[ Pub Med] [ Cross Ref]15.",
"Henry JQ: Spiralian model systems.",
"Int J Dev Biol 2014, 58:389-401.",
"[ Pub Med]16.",
"Smith CM, Lans D, Weisblat DA.",
"Cellular mechanisms of epiboly in leech embryos.",
"Development.",
"1996; 122 :1885–94.",
"[ Pub Med]17.",
"Arenas-Mena C. Brachyury, Tbx2/3 and sall expression during embryogenesis of the indirectly developing polychaete Hydroides elegans.",
"Int J Dev Biol.",
"2013; 57 :73–83.",
"doi: 10.1387/ijdb.120056ca.",
"[ Pub Med] [ Cross Ref]18.",
"Chan XY, Lambert JD.",
"Development of blastomere clones in the Ilyanassa embryo: transformation of the spiralian blastula into the larval body plan.",
"Dev Genes Evol.",
"2014; 224 :159–74.",
"doi: 10.1007/s00427-014-0474-z.",
"[ Pub Med] [ Cross Ref]19.",
"Boyle MJ, Yamaguchi E, Seaver EC.",
"Molecular conservation of metazoan gut formation: evidence from expression of endomesoderm genes in Capitella teleta (Annelida) Evodevo.",
"2014; 5 :39. doi: 10.1186/2041-9139-5-39.",
"[ PMC free article] [ Pub Med] [ Cross Ref]20.",
"Halanych KM, Bacheller JD, Aguinaldo AM, Liva SM, Hillis DM, Lake JA.",
"Evidence from 18S ribosomal DNA that the lophophorates are protostome animals.",
"Science.",
"1995; 267 :1641–3.",
"doi: 10.1126/science.7886451.",
"[ Pub Med] [ Cross Ref]21.",
"Dunn CW, Hejnol A, Matus DQ, Pang K, Browne WE, Smith SA, et al.",
"Broad phylogenomic sampling improves resolution of the animal tree of life.",
"Nature.",
"2008; 452 :745–9.",
"doi: 10.1038/nature06614.",
"[ Pub Med] [ Cross Ref]22.",
"Hejnol A, Martindale MQ.",
"Acoel development indicates the independent evolution of the bilaterian mouth and anus.",
"Nature.",
"2008; 456 :382–6.",
"doi: 10.1038/nature07309.",
"[ Pub Med] [ Cross Ref]23.",
"Arendt D, Technau U, Wittbrodt J. Evolution of the bilaterian larval foregut.",
"Nature.",
"2001; 409 :81–5.",
"doi: 10.1038/35051075.",
"[ Pub Med] [ Cross Ref]24.",
"Byrum CA, Martindale MQ.",
"Gastrulation in Cnidaria and Ctenophora.",
"In: Stern CD, editor.",
"Gastrulation from cells to embryo.",
"New York, NY: Cold Spring Harbor Laboratory Press; 2004.25.",
"Technau U. Brachyury, the blastopore and the evolution of mesoderm.",
"Bioessays.",
"2001; 23 :788–94.",
"doi: 10.1002/bies.1114.",
"[ Pub Med] [ Cross Ref]26.",
"Technau U, Scholz CB.",
"Origin and evolution of endoderm and mesoderm.",
"Int J Dev Biol.",
"2003; 47 :531–9.",
"[ Pub Med]27.",
"Smart TI, von Dassow G. Unusual development of the mitraria larva in the polychaete Owenia collaris.",
"Biol Bull.",
"2009; 217 :253–68.",
"[ Pub Med]28.",
"Hejnol A, Martín-Durán JM: Getting to the bottom of anal evolution.",
"Zool Anzeiger - A J Comp Zool 2015, 256:61-74.29.",
"Nielsen C. Trochophora larvae: cell-lineages, ciliary bands, and body regions.",
"1.",
"Annelida and Mollusca.",
"J Exp Zool B Mol Dev Evol.",
"2004; 302B :35–68.",
"doi: 10.1002/jez.b.20001.",
"[ Pub Med] [ Cross Ref]30.",
"Henry JJ, Collin R, Perry KJ.",
"The slipper snail, Crepidula: an emerging lophotrochozoan model system.",
"Biol Bull.",
"2010; 218 :211–29.",
"[ Pub Med]31.",
"Hejnol A, Martindale MQ, Henry JQ.",
"High-resolution fate map of the snail Crepidula fornicata: the origins of ciliary bands, nervous system, and muscular elements.",
"Dev Biol.",
"2007; 305 :63–76.",
"doi: 10.1016/j.ydbio.2007.01.044.",
"[ Pub Med] [ Cross Ref]32.",
"Henry JQ, Perry KJ, Martindale MQ.",
"Cell specification and the role of the polar lobe in the gastropod mollusc Crepidula fornicata.",
"Dev Biol.",
"2006; 297 :295–307.",
"doi: 10.1016/j.ydbio.2006.04.441.",
"[ Pub Med] [ Cross Ref]33.",
"Henry JQ, Perry KJ, Martindale MQ.",
"Beta-catenin and early development in the gastropod Crepidula fornicata.",
"Integr Comp Biol.",
"2010; 50 :707–19.",
"doi: 10.1093/icb/icq076.",
"[ Pub Med] [ Cross Ref]34.",
"Lyons DC, Perry KJ, Lesoway MP, Henry JQ.",
"Cleavage pattern and fate map of the mesentoblast, 4d, in the gastropod Crepidula: a hallmark of spiralian development.",
"Evodevo.",
"2012; 3 :21. doi: 10.1186/2041-9139-3-21.",
"[ PMC free article] [ Pub Med] [ Cross Ref]35.",
"Martindale MQ, Henry JQ.",
"Modifications of cell fate specification in equal-cleaving nemertean embryos: alternate patterns of spiralian development.",
"Development.",
"1995; 121 :3175–85.",
"[ Pub Med]36.",
"Henry JJ, Martindale MQ.",
"Conservation of the spiralian developmental program: cell lineage of the nemertean, Cerebratulus lacteus.",
"Dev Biol.",
"1998; 201 :253–69.",
"doi: 10.1006/dbio.1998.8966.",
"[ Pub Med] [ Cross Ref]37.",
"Saunders LR, Mc Clay DR. Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition.",
"Development.",
"2014; 141 :1503–13.",
"doi: 10.1242/dev.101436.",
"[ PMC free article] [ Pub Med] [ Cross Ref]38.",
"Burkel BM, Von Dassow G, Bement WM.",
"Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin.",
"Cell Motil Cytoskeleton.",
"2007; 64 :822–832.",
"doi: 10.1002/cm.20226.",
"[ PMC free article] [ Pub Med] [ Cross Ref]39.",
"Miller AL, Bement WM.",
"Regulation of cytokinesis by Rho GTPase flux.",
"Nat Cell Biol.",
"2009; 11 :71–7.",
"doi: 10.1038/ncb1814.",
"[ PMC free article] [ Pub Med] [ Cross Ref]40.",
"Giani VC, Jr, Yamaguchi E, Boyle MJ, Seaver EC.",
"Somatic and germline expression of piwi during development and regeneration in the marine polychaete annelid Capitella teleta.",
"Evodevo.",
"2011; 2 :10. doi: 10.1186/2041-9139-2-10.",
"[ PMC free article] [ Pub Med] [ Cross Ref]41.",
"Molé-Bajer J, Bajer AS.",
"Studies of selected endosperm cells with the light and electron microscope: the technique.",
"Cellule.",
"1968; 67 :257–65.42.",
"Conklin EG.",
"The embryology of Crepidula.",
"J Morphol.",
"1897; 13 :1–226.",
"doi: 10.1002/jmor.1050130102.",
"[ Cross Ref]43.",
"Lartillot N, Lespinet O, Vervoort M, Adoutte A.",
"Expression pattern of Brachyury in the mollusc Patella vulgata suggests a conserved role in the establishment of the AP axis in Bilateria.",
"Development.",
"2002; 129 :1411–21.",
"[ Pub Med]44.",
"Rawlinson KA.",
"Embryonic and post-embryonic development of the polyclad flatworm Maritigrella crozieri; implications for the evolution of spiralian life history traits.",
"Front Zool.",
"2010; 7 :12. doi: 10.1186/1742-9994-7-12.",
"[ PMC free article] [ Pub Med] [ Cross Ref]45.",
"Younossi-Hartenstein A, Hartenstein V. The embryonic development of the polyclad flatworm Imogine mcgrathi.",
"Dev Genes Evol.",
"2000; 210 :383–98.",
"doi: 10.1007/s004270000086.",
"[ Pub Med] [ Cross Ref]46.",
"Lambert JD.",
"Mesoderm in spiralians: the organizer and the 4d cell.",
"J Exp Zool B Mol Dev Evol.",
"2008; 310 :15–23.",
"doi: 10.1002/jez.b.21176.",
"[ Pub Med] [ Cross Ref]47.",
"Arenas-Mena C. Indirect development, transdifferentiation and the macroregulatory evolution of metazoans.",
"Philos Trans R Soc Lond B Biol Sci.",
"2010; 365 :653–69.",
"doi: 10.1098/rstb.2009.0253.",
"[ PMC free article] [ Pub Med] [ Cross Ref]48.",
"Boyer BC, Henry JQ, Martindale MQ.",
"Dual origins of mesoderm in a basal spiralian: cell lineage analyses in the polyclad turbellarian Hoploplana inquilina.",
"Dev Biol.",
"1996; 179 :329–38.",
"doi: 10.1006/dbio.1996.0264.",
"[ Pub Med] [ Cross Ref]49.",
"Boyer BC, Henry JJ, Martindale MQ.",
"The cell lineage of a polyclad turbellarian embryo reveals close similarity to coelomate spiralians.",
"Dev Biol.",
"1998; 204 :111–23.",
"doi: 10.1006/dbio.1998.9084.",
"[ Pub Med] [ Cross Ref]50.",
"Chan XY, Lambert JD.",
"Patterning a spiralian embryo: a segregated RNA for a Tis11 ortholog is required in the 3a and 3b cells of the Ilyanassa embryo.",
"Dev Biol.",
"2011; 349 :102–112.",
"doi: 10.1016/j.ydbio.2010.10.001.",
"[ Pub Med] [ Cross Ref]51.",
"Nederbragt B, Lespinet O, van Wageningen S, van Loon AE, Adoutte A, Dictus WJAG.",
"A lophotrochozoan twist gene is expressed in the ectomesoderm of the gastropod mollusk Patella vulgata.",
"Evol Dev.",
"2002; 4 :334–43.",
"doi: 10.1046/j.1525-142X.2002.02020.x.",
"[ Pub Med] [ Cross Ref]52.",
"Wu SY, Ferkowicz M, Mc Clay DR. Ingression of primary mesenchyme cells of the sea urchin embryo: a precisely timed epithelial mesenchymal transition.",
"Birth Defects Res C Embryo Today.",
"2007; 81 :241–52.",
"doi: 10.1002/bdrc.20113.",
"[ Pub Med] [ Cross Ref]53.",
"Meyer NP, Boyle MJ, Martindale MQ, Seaver EC.",
"A comprehensive fate map by intracellular injection of identified blastomeres in the marine polychaete Capitella teleta.",
"Evodevo.",
"2010; 1 :8. doi: 10.1186/2041-9139-1-8.",
"[ PMC free article] [ Pub Med] [ Cross Ref]54.",
"Woltereck R. Beiträge zur praktischen Analyse der Polygordius Entwicklung nach dem “Nordsee” – und dem “Mittelmeer” – Typus.",
"I.",
"Die für beide Typen gleichverlaufende Entwicklungsabschnitt: Vom Ei bis zum jüngsten Trochophora-Stadium.",
"Arch Entw Mech Org.",
"1904; 18 :377–403.55.",
"Steinmetz PRH, Zelada-Gonzáles F, Burgtorf C, Wittbrodt J, Arendt D, Zelada-Gonzales F. Polychaete trunk neuroectoderm converges and extends by mediolateral cell intercalation.",
"Proc Natl Acad Sci USA.",
"2007; 104 :2727–32.",
"doi: 10.1073/pnas.0606589104.",
"[ PMC free article] [ Pub Med] [ Cross Ref]56.",
"Gharbiah M, Nakamoto A, Nagy LM.",
"Analysis of ciliary band formation in the mollusc Ilyanassa obsoleta.",
"Dev Genes Evol.",
"2013; 223 :225–35.",
"doi: 10.1007/s00427-013-0440-1.",
"[ Pub Med] [ Cross Ref]57.",
"Henry JQ, Hejnol A, Perry KJ, Martindale MQ.",
"Homology of ciliary bands in spiralian trochophores.",
"Integr Comp Biol.",
"2007; 47 :865–71.",
"doi: 10.1093/icb/icm035.",
"[ Pub Med] [ Cross Ref]58.",
"Bhaud M, Cazaux C. Les larves de polychètes des côtes de France.",
"Oceanis.",
"1982; 8 :57–160.59.",
"Gravely F. Studies on polychaete larvae.",
"Q J Microsc Sci.",
"1909; 53 :597–627.60.",
"Nielsen C. Animal evolution.",
"Oxford: Oxford University Press; 1995.61.",
"Nielsen C. Animal phylogeny in the light of the trochaea theory.",
"Biol J Linn Soc.",
"1985; 25 :243–99.",
"doi: 10.1111/j.1095-8312.1985.tb00396.x.",
"[ Cross Ref]62.",
"Nielsen C. Structure and development of metazoan ciliary bands and their phylogenetic significance.",
"Acta Zool.",
"1987; 68 :205–62.",
"doi: 10.1111/j.1463-6395.1987.tb00892.x.",
"[ Cross Ref]63.",
"Strathmann RR.",
"Hypotheses on the origins of marine larvae.",
"Rev Ecol Syst.",
"1993; 24 :89–117.",
"doi: 10.1146/annurev.es.24.110193.000513.",
"[ Cross Ref]64.",
"Dictus WJ, Damen P. Cell-lineage and clonal-contribution map of the trochophore larva of Patella vulgata (mollusca) Mech Dev.",
"1997; 62 :213–26.",
"doi: 10.1016/S0925-4773 (97)00666-7.",
"[ Pub Med] [ Cross Ref]65.",
"Meyer NP, Seaver EC.",
"Cell lineage and fate map of the primary somatoblast of the polychaete annelid Capitella teleta.",
"Integr Comp Biol.",
"2010; 50 :756–67.",
"doi: 10.1093/icb/icq120.",
"[ Pub Med] [ Cross Ref]66.",
"Robert A. Recherches sur le developpement des troques.",
"Archs Zool Exp Gen. 1903; 10 :269–538.67.",
"Rouse GW.",
"Trochophore concepts: ciliary bands and the evolution of larvae in spiralian Metazoa.",
"Biol J Linn Soc.",
"1999; 66 :411–464.",
"doi: 10.1111/j.1095-8312.1999.tb01920.x.",
"[ Cross Ref]68.",
"Cantell CE.",
"Some developmental stages of the peculiar nemertean larvae Pilidium recurvatum Fewkes from the Gullmarfjord (Sweden) Ark för Zool.",
"1967; 19 :143–7.69.",
"Maslakova SA, von Dassow G. A non-feeding pilidium with apparent prototroch and telotroch.",
"J Exp Zool Part B Mol Dev Evol.",
"2012; 318B :586–90.",
"doi: 10.1002/jezb.22467.",
"[ Pub Med] [ Cross Ref]70.",
"Child CM.",
"The early development of Arenicola and Sternaspis.",
"Wilhelm Roux Arch fur Entwicklungsmechanik der Org.",
"1900; 9 :587–722.",
"doi: 10.1007/BF02156195.",
"[ Cross Ref]71.",
"Mead AD.",
"The early development of marine annelids.",
"J Morphol.",
"1897; 8 :227–327.",
"doi: 10.1002/jmor.1050130202.",
"[ Cross Ref]72.",
"Treadwell AL.",
"The cytogeny of Podarke obscura (Verrill) J Morphol.",
"1901; 17 :399–486.",
"doi: 10.1002/jmor.1050170304.",
"[ Cross Ref]73.",
"Wierzejski A. Embryologie von Physa fontinalis L. Z Wiss Zool.",
"1905; 83 :502–706.74.",
"Kingsley EP, Chan XY, Duan Y, Lambert JD.",
"Widespread RNA segregation in a spiralian embryo.",
"Evol Dev.",
"2007; 9 :527–39.",
"doi: 10.1111/j.1525-142X.2007.00194.x.",
"[ Pub Med] [ Cross Ref]75.",
"Le Gouar M, Lartillot N, Adoutte A, Vervoort M. The expression of a caudal homologue in a mollusc, Patella vulgata.",
"Gene Expr Patterns.",
"2003; 3 :35–7.",
"doi: 10.1016/S1567-133X (02)00091-1.",
"[ Pub Med] [ Cross Ref]76.",
"Perry, KJ, Lyons, DC Fischer, AHL, Helfrich, LW, Johansson, KB, Diamond, JC, Henry, JQ.",
"Deployment of regulatory genes during gastrulation and germ layer specification in a model spiralian mollusc Crepidula.",
"Dev Dyn, doi:10.1002/dvdy.24308.",
"[ Pub Med]"
] |
D1148690
|
http://www.wellnessresources.com/studies/taurine_activates_gaba_receptors/
|
Taurine Activates GABA Receptors
|
"Study Title: Taurine Activates GABA Receptors Study Abstract Taurine is one of the most abundant free amino acids in the brain. In a number of studies, taurine has been reported to activate glycine receptors (Gly-Rs) at moderate concentrations (> or = 100 micro M), and to be a weak agonist at GABA (A) receptors (GABA (A)-Rs), which are usually activated at high concentrations (> or = 1 m M). In this study, we show that taurine reduced the excitability of thalamocortical relay neurons and activated both extrasynaptic GABA (A)-Rs and Gly-Rs in neurons in the mouse ventrobasal (VB) thalamus. Low concentrations of taurine (10-100 micro M) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage clamp, but had no effects on fast inhibitory synaptic currents. Currents elicited by 50 micro M taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 micro M Zn2+, consistent with the pharmacological properties of extrasynaptic GABA (A)-Rs (alpha4beta2delta subtype) involved in tonic inhibition in the thalamus. Tonic inhibition was enhanced by an inhibitor of taurine transport, suggesting that taurine can act as an endogenous activator of these receptors. Taurine-evoked currents were absent in relay neurons from GABA (A)-R alpha4 subunit knock-out mice. The amplitude of the taurine current was larger in neurons from adult mice than juvenile mice. Taurine was a more potent agonist at recombinant alpha4beta2delta GABA (A)-Rs than at alpha1beta2gamma2 GABA (A)-Rs. We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA (A)-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus. From press release: Taurine is one of the most plentiful amino acids in the human brain, but neuroscientists are still puzzled by just how brain cells put it to use. Now, a team of researchers at Weill Cornell Medical College (WCMC) has uncovered a prime site of activity for the molecule, bringing them closer to solving that mystery. ""We have discovered that taurine is a strong activator of what are known as GABA [gamma-aminobutyric acid] receptors in a regulatory area of the brain called the thalamus,"" said study senior author Neil L. Harrison, professor of pharmacology and pharmacology in anesthesiology at WCMC. ""We had discovered these receptors two years ago and showed that they interact with the neurotransmitter GABA -- the brain's key inhibitory transmitter -- that is also involved in brain development. It seems that taurine shares these receptors. ""The finding, reported in the January issue of the Journal of Neuroscience , opens the door to better understanding taurine's impact on the brain. While the amino acid is made naturally by the body, it's also a much-touted ingredient in such so-called ""energy drinks"" as Red Bull. ""Its inclusion in these supplements is a little puzzling, because our research would suggest ... [that] taurine actually would have more of a sedative effect on the brain,"" Harrison said. The prime focus of the study, however, was to find a site for the neurological activity of taurine. ""Scientists have long questioned whether taurine might act on an as-yet-undiscovered receptor of its own,"" said lead researcher Fan Jia, postdoctoral scientist in anesthesiology. ""But after some recent work in our lab, we ended up zeroing in on this population of GABA receptors in the thalamus. ""The thalamus, located deep in the brain's center, is involved in what neuroscientists call ""behavioral state control,"" helping to regulate transitions between sleep and wakefulness, for example. ""It's like a railway junction, controlling information traffic between the brainstem, the senses and the executive functions in the cortex,"" Harrison said. The researchers exposed thin slices of thalamic tissue from the brains of mice to concentrations of taurine that were similar to what might be found in the human brain. ""We found that taurine is extraordinarily active on this population of GABA receptors in the thalamus,"" Harrison said. ""It came as a bit of a surprise that the same receptor was used by both taurine and GABA. Nevertheless, finding taurine's receptor has been like discovering the 'missing link' in taurine biology. ""Now, Harrison's group is trying to determine what taurine actually does in the brain; Harrison said that because GABA is important for forging new cell-to-cell connections in the developing brain, ""and because taurine shares a receptor with GABA, it, too, may play a role in neurological development. ""As for energy drinks, ""Remarkably little is known about the effects of energy drinks on the brain,"" Harrison said. ""Assuming that some of [taurine] does get absorbed, the taurine ... may actually play a role in the crash people often report after drinking these highly caffeinated beverages. ""The work was funded by the U. S. National Institutes of Health. Co-researchers include Minerva Yue, Angelo Keramidas and Peter A. Goldstein of WCMC as well as Dev Chandra and Gregg E. Homanics of the University of Pittsburgh. Study Information Jia F, Yue M, Chandra D, Keramidas A, Goldstein PA, Homanics GE, Harrison NL. Taurine is a potent activator of extrasynaptic GABA (A) receptors in the thalamus. J Neurosci. 2008 January C. V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10065-4897, USA. Full Studyhttp://www.jneurosci.org/cgi/content/full/28/1/106 "
|
[
"\"Study Title: Taurine Activates GABA Receptors Study Abstract Taurine is one of the most abundant free amino acids in the brain.",
"In a number of studies, taurine has been reported to activate glycine receptors (Gly-Rs) at moderate concentrations (> or = 100 micro M), and to be a weak agonist at GABA (A) receptors (GABA (A)-Rs), which are usually activated at high concentrations (> or = 1 m M).",
"In this study, we show that taurine reduced the excitability of thalamocortical relay neurons and activated both extrasynaptic GABA (A)-Rs and Gly-Rs in neurons in the mouse ventrobasal (VB) thalamus.",
"Low concentrations of taurine (10-100 micro M) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage clamp, but had no effects on fast inhibitory synaptic currents.",
"Currents elicited by 50 micro M taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 micro M Zn2+, consistent with the pharmacological properties of extrasynaptic GABA (A)-Rs (alpha4beta2delta subtype) involved in tonic inhibition in the thalamus.",
"Tonic inhibition was enhanced by an inhibitor of taurine transport, suggesting that taurine can act as an endogenous activator of these receptors.",
"Taurine-evoked currents were absent in relay neurons from GABA (A)-R alpha4 subunit knock-out mice.",
"The amplitude of the taurine current was larger in neurons from adult mice than juvenile mice.",
"Taurine was a more potent agonist at recombinant alpha4beta2delta GABA (A)-Rs than at alpha1beta2gamma2 GABA (A)-Rs.",
"We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA (A)-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus.",
"From press release: Taurine is one of the most plentiful amino acids in the human brain, but neuroscientists are still puzzled by just how brain cells put it to use.",
"Now, a team of researchers at Weill Cornell Medical College (WCMC) has uncovered a prime site of activity for the molecule, bringing them closer to solving that mystery.",
"\"\"We have discovered that taurine is a strong activator of what are known as GABA [gamma-aminobutyric acid] receptors in a regulatory area of the brain called the thalamus,\"\" said study senior author Neil L. Harrison, professor of pharmacology and pharmacology in anesthesiology at WCMC.",
"\"\"We had discovered these receptors two years ago and showed that they interact with the neurotransmitter GABA -- the brain's key inhibitory transmitter -- that is also involved in brain development.",
"It seems that taurine shares these receptors.",
"\"\"The finding, reported in the January issue of the Journal of Neuroscience , opens the door to better understanding taurine's impact on the brain.",
"While the amino acid is made naturally by the body, it's also a much-touted ingredient in such so-called \"\"energy drinks\"\" as Red Bull.",
"\"\"Its inclusion in these supplements is a little puzzling, because our research would suggest ... [that] taurine actually would have more of a sedative effect on the brain,\"\" Harrison said.",
"The prime focus of the study, however, was to find a site for the neurological activity of taurine.",
"\"\"Scientists have long questioned whether taurine might act on an as-yet-undiscovered receptor of its own,\"\" said lead researcher Fan Jia, postdoctoral scientist in anesthesiology.",
"\"\"But after some recent work in our lab, we ended up zeroing in on this population of GABA receptors in the thalamus.",
"\"\"The thalamus, located deep in the brain's center, is involved in what neuroscientists call \"\"behavioral state control,\"\" helping to regulate transitions between sleep and wakefulness, for example.",
"\"\"It's like a railway junction, controlling information traffic between the brainstem, the senses and the executive functions in the cortex,\"\" Harrison said.",
"The researchers exposed thin slices of thalamic tissue from the brains of mice to concentrations of taurine that were similar to what might be found in the human brain.",
"\"\"We found that taurine is extraordinarily active on this population of GABA receptors in the thalamus,\"\" Harrison said.",
"\"\"It came as a bit of a surprise that the same receptor was used by both taurine and GABA.",
"Nevertheless, finding taurine's receptor has been like discovering the 'missing link' in taurine biology.",
"\"\"Now, Harrison's group is trying to determine what taurine actually does in the brain; Harrison said that because GABA is important for forging new cell-to-cell connections in the developing brain, \"\"and because taurine shares a receptor with GABA, it, too, may play a role in neurological development.",
"\"\"As for energy drinks, \"\"Remarkably little is known about the effects of energy drinks on the brain,\"\" Harrison said.",
"\"\"Assuming that some of [taurine] does get absorbed, the taurine ... may actually play a role in the crash people often report after drinking these highly caffeinated beverages.",
"\"\"The work was funded by the U. S. National Institutes of Health.",
"Co-researchers include Minerva Yue, Angelo Keramidas and Peter A. Goldstein of WCMC as well as Dev Chandra and Gregg E. Homanics of the University of Pittsburgh.",
"Study Information Jia F, Yue M, Chandra D, Keramidas A, Goldstein PA, Homanics GE, Harrison NL.",
"Taurine is a potent activator of extrasynaptic GABA (A) receptors in the thalamus.",
"J Neurosci.",
"2008 January C. V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10065-4897, USA.",
"Full Studyhttp://www.jneurosci.org/cgi/content/full/28/1/106 \""
] |
D131782
|
http://www.health.ny.gov/prevention/public_health_works/careers/public_health_sanitarian.htm
|
Public Health Sanitarian Series
|
You are Here: Home Page > Public Health Careers > Public Health Sanitarian Series Public Health Sanitarian Series Environmental Health Careers with State and County Health Departments Employing science and engineering graduates from a variety of disciplines, environmental health programs offer meaningful and satisfying careers helping protect people and communities from public health risks. They provide an attractive variety of work assignments and settings, and ample opportunity for professional development and advancement. State positions and most county jobs offer excellent fringe benefits including subsidized health insurance coverage, reasonable and flexible work hours, generous amounts of leave time, and unrivaled pension plans. In combination, these factors allow science and technology graduates to experience gratifying careers while enjoying an enviable quality of life. Recent surveys indicate there is a substantial shortfall of candidates for these jobs. Job Description Sanitarians promote public health by conducting environmental health inspections and related activities for settings such as food service establishments (restaurants), children's camps, hotels, campgrounds, swimming pools, bathing beaches, water and sewage treatment systems, hospitals, long term and adult care facilities, and diagnostic and treatment centers. Their work includes: determining compliance with the Public Health Law, the State Sanitary Code and Medical Facilities Codes; preparing inspection reports that cite violations, document deficiencies, and recommend improvements; and reviewing written plans related to facility operation, construction design, and facility corrections. Sanitarians may also conduct investigations of illness outbreaks, children's camp injuries, environmental conditions conducive to childhood lead poisoning, or chemical exposures, and they respond to public health nuisances, indoor air violation complaints and public health emergencies. Related Titles Titles in the NYSDOH sanitarian series requiring limited or no experience include Sanitarian Trainee (exam 24-387), Public Health Sanitarian (exam 24-388), and Senior Sanitarian (exam 24-389). Higher promotional levels are available for more experienced employees ( Principal and Chief Sanitarian ). Some county health departments use these titles also. Other county health departments and New York City use various other Public Health Sanitarian titles, or related titles such as Environmental Health Specialist. Qualifications Candidates generally must possess a bachelor's degree that includes 30 credit hours in the natural sciences (NYS allows up to 12 credit hours of the 30 to be in the applied sciences, and may allow certain exceptions to the degree requirement). Acceptable natural sciences include biology, chemistry, geology, hydrology or physics. Acceptable applied sciences include environmental technology, sanitation technology, medical technology, public health, infection control or food science. The higher level titles also require varying amounts of relevant experience. Applicants must satisfactorily complete a written civil service exam to be placed on a list of eligible candidates. Locations/Availability Hundreds of sanitarians are employed across the state. Openings for these positions are regularly available at 36 county health departments, and with the NYSDOH at more than a dozen field offices and the agency's Center for Environmental Health [CEH] in Troy. Salaries Effective April 2009 the salary for the NYSDOH (state) entry level Sanitarian Trainee (grade 13) ranged from about $37,400 to $47,500. Upon completion of a one-year traineeship, trainees advance without further examination to Public Health Sanitarian (grade 14, 2009 salary range about $39,600 to $50,300). Salary increases occur within these ranges based on progressive years of satisfactory experience, and the salary ranges increase periodically in accordance with union-negotiated contracts. Promotion to the higher level titles with greater responsibility and complexity is based on experience, additional exams, and the civil service process. Top salary for a NYSDOH Principal Sanitarian (grade 23) in 2009 was about $78,400. Salaries for sanitarians in county health departments vary depending on location, title and grade level. Contact & Application Information Written exams are conducted and vacancy announcements issued periodically. Both types of announcements for state positions can be found on the NYSDOH employment web page. Additional information on environmental health jobs and activities can be found at the Public Health Works! page. Questions about employment opportunities with the NYSDOH may be e-mailed to [email protected] or your may contact the agency's Bureau of Personnel Management at 518-486-1812. Information on employment opportunities at county health departments can be obtained by contacting the individual county civil service agency. Contact information for these can be found through the New York State Department of Civil Service web site. Some county job postings, as well as other information on county health department work, can be found on the New York State Association of County Health Officials (NYSACHO) web site. New York City job postings and related information are found at http://www.nyc.gov/html/doh/html/hr/index.html, or information can be obtained at (212) 788-4655.
|
[
"You are Here: Home Page > Public Health Careers > Public Health Sanitarian Series Public Health Sanitarian Series Environmental Health Careers with State and County Health Departments Employing science and engineering graduates from a variety of disciplines, environmental health programs offer meaningful and satisfying careers helping protect people and communities from public health risks.",
"They provide an attractive variety of work assignments and settings, and ample opportunity for professional development and advancement.",
"State positions and most county jobs offer excellent fringe benefits including subsidized health insurance coverage, reasonable and flexible work hours, generous amounts of leave time, and unrivaled pension plans.",
"In combination, these factors allow science and technology graduates to experience gratifying careers while enjoying an enviable quality of life.",
"Recent surveys indicate there is a substantial shortfall of candidates for these jobs.",
"Job Description Sanitarians promote public health by conducting environmental health inspections and related activities for settings such as food service establishments (restaurants), children's camps, hotels, campgrounds, swimming pools, bathing beaches, water and sewage treatment systems, hospitals, long term and adult care facilities, and diagnostic and treatment centers.",
"Their work includes: determining compliance with the Public Health Law, the State Sanitary Code and Medical Facilities Codes; preparing inspection reports that cite violations, document deficiencies, and recommend improvements; and reviewing written plans related to facility operation, construction design, and facility corrections.",
"Sanitarians may also conduct investigations of illness outbreaks, children's camp injuries, environmental conditions conducive to childhood lead poisoning, or chemical exposures, and they respond to public health nuisances, indoor air violation complaints and public health emergencies.",
"Related Titles Titles in the NYSDOH sanitarian series requiring limited or no experience include Sanitarian Trainee (exam 24-387), Public Health Sanitarian (exam 24-388), and Senior Sanitarian (exam 24-389).",
"Higher promotional levels are available for more experienced employees ( Principal and Chief Sanitarian ).",
"Some county health departments use these titles also.",
"Other county health departments and New York City use various other Public Health Sanitarian titles, or related titles such as Environmental Health Specialist.",
"Qualifications Candidates generally must possess a bachelor's degree that includes 30 credit hours in the natural sciences (NYS allows up to 12 credit hours of the 30 to be in the applied sciences, and may allow certain exceptions to the degree requirement).",
"Acceptable natural sciences include biology, chemistry, geology, hydrology or physics.",
"Acceptable applied sciences include environmental technology, sanitation technology, medical technology, public health, infection control or food science.",
"The higher level titles also require varying amounts of relevant experience.",
"Applicants must satisfactorily complete a written civil service exam to be placed on a list of eligible candidates.",
"Locations/Availability Hundreds of sanitarians are employed across the state.",
"Openings for these positions are regularly available at 36 county health departments, and with the NYSDOH at more than a dozen field offices and the agency's Center for Environmental Health [CEH] in Troy.",
"Salaries Effective April 2009 the salary for the NYSDOH (state) entry level Sanitarian Trainee (grade 13) ranged from about $37,400 to $47,500.",
"Upon completion of a one-year traineeship, trainees advance without further examination to Public Health Sanitarian (grade 14, 2009 salary range about $39,600 to $50,300).",
"Salary increases occur within these ranges based on progressive years of satisfactory experience, and the salary ranges increase periodically in accordance with union-negotiated contracts.",
"Promotion to the higher level titles with greater responsibility and complexity is based on experience, additional exams, and the civil service process.",
"Top salary for a NYSDOH Principal Sanitarian (grade 23) in 2009 was about $78,400.",
"Salaries for sanitarians in county health departments vary depending on location, title and grade level.",
"Contact & Application Information Written exams are conducted and vacancy announcements issued periodically.",
"Both types of announcements for state positions can be found on the NYSDOH employment web page.",
"Additional information on environmental health jobs and activities can be found at the Public Health Works!",
"page.",
"Questions about employment opportunities with the NYSDOH may be e-mailed to [email protected] or your may contact the agency's Bureau of Personnel Management at 518-486-1812.",
"Information on employment opportunities at county health departments can be obtained by contacting the individual county civil service agency.",
"Contact information for these can be found through the New York State Department of Civil Service web site.",
"Some county job postings, as well as other information on county health department work, can be found on the New York State Association of County Health Officials (NYSACHO) web site.",
"New York City job postings and related information are found at http://www.nyc.gov/html/doh/html/hr/index.html, or information can be obtained at (212) 788-4655."
] |
D2169873
|
http://www.politifact.com/truth-o-meter/article/2012/jul/01/fact-checking-immigration/
|
Fact-checking immigration
|
"Fact-checking immigration By Becky Bowers on Thursday, June 20th, 2013 at 4:55 p.m. Immigration legislation would address border enforcement and people living in the United States illegally. As the Senate considers a sweeping immigration bill, here’s a roundup of our recent fact-checks on immigration: Immigrants are ‘more fertile’: Jeb Bush, former Republican governor of Florida, recently claimed immigration reform would help aging America’s ""demographic pyramid."" ""Immigrants are more fertile,"" he said. ""And they love families and they have more intact families, and they bring a younger population. Immigrants create an engine of economic prosperity. ""Related rulings: On immigration reform, Marco Rubio ""all along has been saying, 'We have to have border security first' "" and then ""he gets on Spanish TV, he ends up saying, 'No, no. That will never get in the way.' ""— Dana Rohrabacher, Sunday, June 16th, 2013. ""Immigrants are more fertile. ""— Jeb Bush, Friday, June 14th, 2013. ""Ronald Reagan’s signature on the 1986 amnesty act"" gave Barack Obama about 15 million additional Hispanic votes in 2012.— Steve King, Thursday, May 23rd, 2013. Says ""we allow more people into America legally than all other countries on the planet combined. ""— Greg Walden, Thursday, April 18th, 2013. Among Hispanics, support for immigration reform is close to universal.— Bill Richardson, Sunday, May 5th, 2013. See related rulings Using fertility as a synonym for birth rate, the stats back him up, showing birth rates among foreign-born residents are about 50 percent higher than for U. S.-born women. However, the rates are converging, and they vary widely among immigrant groups. We rated Bush’s statement Mostly True. Almost every Hispanic supports reform: Former Democratic cabinet member and New Mexico Gov. Bill Richardson said in a May interview that, ""almost every Hispanic in the country wants to see immigration reform. ""Reliable polls show strong and consistent majority support for a variety of policies that might be characterized as ""immigration reform."" In some cases, the level of support reached 90 percent. But while the level of dissent among Hispanics is small, it's not as infinitesimal as Richardson’s comment suggests. We rated his claim Mostly True. Sen. Marco Rubio, misleading in two languages? U. S. Rep. Dana Rohrabacher, a California Republican, recently accused Rubio of contradicting his pledge to put border security before legalization for undocumented immigrants. Rubio ""all along has been saying, 'We have to have border security first,’ "" Rep. Dana Rohrabacher told conservative WND Radio on June 16, 2013. ""And then, he, you know, when he gets on Spanish TV, he ends up saying, 'No, no. That will never get in the way' or, 'Legalization status isn't contingent on border control.' Well, this is outrageous, and no one should believe him. ""Rubio emphasized different parts of the bill’s process depending on his audience. But his explanations described the bill’s provisions the same way, in English and in Spanish. We rated Rohrabacher’s claim Mostly False. More legal immigrants into U. S. than everywhere else combined? U. S. Rep. Greg Walden, R-Ore., said in May that ""we allow more people into America legally than all other countries on the planet combined. ""That’s true only when specifically talking about a small group of countries that have a green-card-like immigration system that provides a path to citizenship. When we compared permanent immigrants in other countries — green-card and permanent-type residents — we found that his statement wasn’t accurate without significant context. We rated his claim Mostly False.1986 amnesty assured Obama’s re-election? U. S. Rep. Steve King, R-Iowa, claimed in May that one of his conservative heroes, President Ronald Reagan, had helped re-elect Barack Obama. ""Reagan’s signature on the 1986 amnesty act brought about Barack Obama’s election,"" King said. The Immigration Reform and Control Act gave legal status to many illegal immigrants who were then residing in the United States. It’s no secret that long-term growth in the Hispanic population — stemming from overall immigration policies, higher birth rates and other factors — has aided Obama’s electoral prospects. However, very little of this growth stems from the law Reagan signed, and King’s estimate of the number of family members indirectly legalized by the law is far too high. We rated King’s claim False. "
|
[
"\"Fact-checking immigration By Becky Bowers on Thursday, June 20th, 2013 at 4:55 p.m. Immigration legislation would address border enforcement and people living in the United States illegally.",
"As the Senate considers a sweeping immigration bill, here’s a roundup of our recent fact-checks on immigration: Immigrants are ‘more fertile’: Jeb Bush, former Republican governor of Florida, recently claimed immigration reform would help aging America’s \"\"demographic pyramid.\"\"",
"\"\"Immigrants are more fertile,\"\" he said.",
"\"\"And they love families and they have more intact families, and they bring a younger population.",
"Immigrants create an engine of economic prosperity.",
"\"\"Related rulings: On immigration reform, Marco Rubio \"\"all along has been saying, 'We have to have border security first' \"\" and then \"\"he gets on Spanish TV, he ends up saying, 'No, no.",
"That will never get in the way.'",
"\"\"— Dana Rohrabacher, Sunday, June 16th, 2013.",
"\"\"Immigrants are more fertile.",
"\"\"— Jeb Bush, Friday, June 14th, 2013.",
"\"\"Ronald Reagan’s signature on the 1986 amnesty act\"\" gave Barack Obama about 15 million additional Hispanic votes in 2012.— Steve King, Thursday, May 23rd, 2013.",
"Says \"\"we allow more people into America legally than all other countries on the planet combined.",
"\"\"— Greg Walden, Thursday, April 18th, 2013.",
"Among Hispanics, support for immigration reform is close to universal.— Bill Richardson, Sunday, May 5th, 2013.",
"See related rulings Using fertility as a synonym for birth rate, the stats back him up, showing birth rates among foreign-born residents are about 50 percent higher than for U. S.-born women.",
"However, the rates are converging, and they vary widely among immigrant groups.",
"We rated Bush’s statement Mostly True.",
"Almost every Hispanic supports reform: Former Democratic cabinet member and New Mexico Gov.",
"Bill Richardson said in a May interview that, \"\"almost every Hispanic in the country wants to see immigration reform.",
"\"\"Reliable polls show strong and consistent majority support for a variety of policies that might be characterized as \"\"immigration reform.\"\"",
"In some cases, the level of support reached 90 percent.",
"But while the level of dissent among Hispanics is small, it's not as infinitesimal as Richardson’s comment suggests.",
"We rated his claim Mostly True.",
"Sen. Marco Rubio, misleading in two languages?",
"U. S. Rep. Dana Rohrabacher, a California Republican, recently accused Rubio of contradicting his pledge to put border security before legalization for undocumented immigrants.",
"Rubio \"\"all along has been saying, 'We have to have border security first,’ \"\" Rep. Dana Rohrabacher told conservative WND Radio on June 16, 2013.",
"\"\"And then, he, you know, when he gets on Spanish TV, he ends up saying, 'No, no.",
"That will never get in the way' or, 'Legalization status isn't contingent on border control.'",
"Well, this is outrageous, and no one should believe him.",
"\"\"Rubio emphasized different parts of the bill’s process depending on his audience.",
"But his explanations described the bill’s provisions the same way, in English and in Spanish.",
"We rated Rohrabacher’s claim Mostly False.",
"More legal immigrants into U. S. than everywhere else combined?",
"U. S. Rep. Greg Walden, R-Ore., said in May that \"\"we allow more people into America legally than all other countries on the planet combined.",
"\"\"That’s true only when specifically talking about a small group of countries that have a green-card-like immigration system that provides a path to citizenship.",
"When we compared permanent immigrants in other countries — green-card and permanent-type residents — we found that his statement wasn’t accurate without significant context.",
"We rated his claim Mostly False.1986 amnesty assured Obama’s re-election?",
"U. S. Rep. Steve King, R-Iowa, claimed in May that one of his conservative heroes, President Ronald Reagan, had helped re-elect Barack Obama.",
"\"\"Reagan’s signature on the 1986 amnesty act brought about Barack Obama’s election,\"\" King said.",
"The Immigration Reform and Control Act gave legal status to many illegal immigrants who were then residing in the United States.",
"It’s no secret that long-term growth in the Hispanic population — stemming from overall immigration policies, higher birth rates and other factors — has aided Obama’s electoral prospects.",
"However, very little of this growth stems from the law Reagan signed, and King’s estimate of the number of family members indirectly legalized by the law is far too high.",
"We rated King’s claim False. \""
] |
D2374820
|
https://www.reference.com/pets-animals/many-mosquitos-bats-eat-night-d1e92a5f7b73fac2
|
How Many Mosquitos Do Bats Eat a Night?
|
Pets & Animals Mammals Bats Q: How Many Mosquitos Do Bats Eat a Night? A: Quick Answer A little brown bat can consume between 600 to 1,000 mosquitoes in a single hour. A nursing little brown bat mother may consume as many as 4,500 mosquitoes in a single evening, more than her own body weight in insects. Continue Reading Keep Learning How Many Bugs Does a Bat Eat in a Night? Why Are Bats Nocturnal? Why Do Bats Only Come Out at Night? Full Answer There are about 1,240 species of bats worldwide, comprising approximately 20 percent of all classified species of mammal. About 70 percent of bats are insectivores that use echolocation to hunt. Most insect-eating bats sleep during the daytime and are only active for a few hours in the evening when insects are the most plentiful. Most are opportunistic feeders, preying on mosquitoes, moths, beetles or any other insects they can catch. Learn more about Bats Sources: batrescue.org en.wikipedia.org ucmp.berkeley.edu Related Questions Q: How Can You Make a Bat Box? A: To make a bat house of moderate difficulty, anticipate working for a 3 to 4 hour time frame and spending approximately 60 dollars. When finished, the inter... Full Answer >Filed Under: Bats Q: How Do Bats Catch Their Prey at Night? A: Although no living bats are completely blind, most bats rely on sounds to find their prey at night. Known as echolocation, ultrasonic sounds are emitted by... Full Answer >Filed Under: Bats Q: What Animals Eat Bats? A: Several types of animals eat bats as part of their diet, including owls, hawks, snakes and spiders. Although bats have many predators, there are only a cou... Full Answer >Filed Under: Bats Q: What Do Bats Eat? A: Different types of bats eat different foods, and their diets may include insects, fruits or blood. Some bats have diets that are beneficial to humans, feed... Full Answer >Filed Under: Bats You May Also Like Q: What Causes a Dry Tongue at Night? Q: What Animals Eat Bats? Q: What Does It Mean If Your Feet Itch at Night? Q: Why Does the Planet Have Day and Night? Q: How Do Bats Navigate? Q: What Is the Average Cost for a Hospital Stay Per Night?
|
[
"Pets & Animals Mammals Bats Q: How Many Mosquitos Do Bats Eat a Night?",
"A: Quick Answer A little brown bat can consume between 600 to 1,000 mosquitoes in a single hour.",
"A nursing little brown bat mother may consume as many as 4,500 mosquitoes in a single evening, more than her own body weight in insects.",
"Continue Reading Keep Learning How Many Bugs Does a Bat Eat in a Night?",
"Why Are Bats Nocturnal?",
"Why Do Bats Only Come Out at Night?",
"Full Answer There are about 1,240 species of bats worldwide, comprising approximately 20 percent of all classified species of mammal.",
"About 70 percent of bats are insectivores that use echolocation to hunt.",
"Most insect-eating bats sleep during the daytime and are only active for a few hours in the evening when insects are the most plentiful.",
"Most are opportunistic feeders, preying on mosquitoes, moths, beetles or any other insects they can catch.",
"Learn more about Bats Sources: batrescue.org en.wikipedia.org ucmp.berkeley.edu Related Questions Q: How Can You Make a Bat Box?",
"A: To make a bat house of moderate difficulty, anticipate working for a 3 to 4 hour time frame and spending approximately 60 dollars.",
"When finished, the inter... Full Answer >Filed Under: Bats Q: How Do Bats Catch Their Prey at Night?",
"A: Although no living bats are completely blind, most bats rely on sounds to find their prey at night.",
"Known as echolocation, ultrasonic sounds are emitted by... Full Answer >Filed Under: Bats Q: What Animals Eat Bats?",
"A: Several types of animals eat bats as part of their diet, including owls, hawks, snakes and spiders.",
"Although bats have many predators, there are only a cou... Full Answer >Filed Under: Bats Q: What Do Bats Eat?",
"A: Different types of bats eat different foods, and their diets may include insects, fruits or blood.",
"Some bats have diets that are beneficial to humans, feed... Full Answer >Filed Under: Bats You May Also Like Q: What Causes a Dry Tongue at Night?",
"Q: What Animals Eat Bats?",
"Q: What Does It Mean If Your Feet Itch at Night?",
"Q: Why Does the Planet Have Day and Night?",
"Q: How Do Bats Navigate?",
"Q: What Is the Average Cost for a Hospital Stay Per Night?"
] |
D712256
|
http://www.hopkinsmedicine.org/healthlibrary/test_procedures/gastroenterology/barium_swallow_92,P07688/
|
Barium Swallow
|
See related health topics and resources<< Back to Gastroenterology Tests and Procedures (Cine esophagram, swallowing study, Esophagography)What is a barium swallow? A barium swallow is an imaging test that uses X-rays to look at your upper gastrointestinal (GI) tract. Your upper GI tract includes the back of your mouth and throat (pharynx) and your esophagus. You may have just a barium swallow. Or this test may be done as part of an upper GI series. This series looks at your esophagus, stomach, and the first part of the small intestine (duodenum). X-rays use a small amount of radiation to create images of your bones and internal organs. X-rays are most often used to find bone or joint problems, or to check the heart and lungs. A barium swallow is one type of X-ray. Fluoroscopy is often used during a barium swallow. Fluoroscopy is a kind of X-ray “movie.”The test also uses barium. Barium is a substance that makes certain area of the body show up more clearly on an X-ray. The radiologist will be able to see size and shape of the pharynx and esophagus. He or she will also be able see how you swallow. These details might not be seen on a standard X-ray. Barium is used only for imaging tests for the GI tract. Why might I need a barium swallow? A barium swallow may be done to look for and diagnose problems in the pharynx and esophagus. You may need a barium swallow if your healthcare provider think that you have: Cancer of the head and neck, pharynx, or esophagus Hiatal hernia. This means that your stomach has moved up into or alongside the esophagus. Structural problems, such as pouches (diverticula), narrowing (strictures), or growths (polyps)Enlarged veins (esophageal varices)Muscle disorders, such as difficulty swallowing ( dysphagia) or spasms Achalasia. This is a condition in which the lower esophageal sphincter muscle doesn't relax and allow food to pass into the stomach. Gastroesophageal reflux disease (GERD) and ulcers Your healthcare provider may have other reasons to recommend a barium swallow. More Information About Digestive Health from Johns Hopkins Medicine Motility Mysteries: Solved!Digestive problems can be maddeningly hard to pin down. Often, symptoms that manifest as gut troubles are actually signs of illness somewhere else. Explore four complex cases that stumped some of the country's leading GI experts. Read more. What are the risks of a barium swallow? You may want to ask your healthcare provider about the amount of radiation used during the test. Also ask about the risks as they apply to you. Consider writing down all X-rays you get, including past scans and X-rays for other health reasons. Show this list to your provider. The risks of radiation exposure may be tied to the number of X-rays you have and the X-ray treatments you have over time. Tell your provider if: You are pregnant or think you may be pregnant. Radiation exposure during pregnancy may lead to birth defects. You are allergic to or sensitive to medicines, contrast dyes, local anesthesia, iodine, or latex You may have constipation or impacted stool after the test if all of the barium does not pass out of your body. You should not have a barium swallow if you have: A tear or hole in your esophagus or intestines (perforation)Blockage in your intestines or severe constipation Severe problems with swallowing. This makes it more likely that barium would accidentally go into your lungs (aspiration). You should also not have this test if you are pregnant. You may have other risks depending on your specific health condition. Be sure to talk with your provider about any concerns you have before the procedure. More Information About Gastrointestinal Diagnostic Exams in the Health Library Abdominal Ultrasound Abdominal X-ray Barium Enema CT Scan of the Abdomen Fluoroscopy Procedure How do I get ready for a barium swallow? Your healthcare provider will explain the procedure to you. Ask him or her any questions you have about the procedure. You may be asked to sign a consent form that gives permission to do the procedure. Read the form carefully and ask questions if anything is not clear. You will need to stop eating and drinking for about 8 hours before the test. Generally, this means after midnight. Tell your provider if you are pregnant or think you may be pregnant. Tell your provider if you are sensitive to or are allergic to any medicines, latex, tape, or anesthetic medicines (local and general). Tell your provider about all medicines you are taking. This includes prescriptions, over-the-counter medicines, and herbal supplements. You may need to stop taking these before the test. Tell your healthcare provider if you have had a recent barium swallow or upper GI test. This may make it harder to get good X-rays of the lower GI area. Follow any other instructions your provider gives you to get ready. What happens during a barium swallow? You may have a barium swallow as an outpatient or as part of your stay in a hospital. The way the test is done may vary depending on your condition and your healthcare provider's practices. Generally, a barium swallow follows this process: You'll be asked to remove any clothing, jewelry, or other objects that may get in the way of the test. You may be asked to remove clothing. If so, you will be given a gown to wear. You will lie on an X-ray table that can move you from a horizontal to an upright position. You may also be asked to change positions during the test. For example, you may need to lie on your side, back, or stomach. The radiologist may take X-rays of your chest and belly (abdomen) first. The radiologist will ask you to take a swallow of a thick, chalky barium drink. The barium is usually flavored, but it may not taste very good. As you swallow the barium, the radiologist will take single pictures, a series of X-rays, or fluoroscopy to watch the barium moving through your mouth and throat. You may be asked to hold your breath at certain times during the test. You will be given a thinner barium drink to swallow. The radiologist will use X-rays or fluoroscopy to watch the barium go down your esophagus. You may also be asked to swallow a barium tablet. This is a small pill that can help to show certain problems in the esophagus. Once the radiologist has taken all of the X-rays, you'll be helped from the table. What happens after a barium swallow? You may go back to your normal diet and activities after a barium swallow, unless your healthcare provider tells you otherwise. Barium may cause constipation or impacted stool after the procedure if it isn't completely cleared from your body. You may be told to drink plenty of fluids and eat foods high in fiber to help the rest of the barium leave your body. You may also be given a laxative to help with this. Your bowel movements may be white or lighter in color until all the barium has left your body. Call your healthcare provider right away if any of these happen: Trouble with bowel movements or you are unable to have a bowel movement or pass gas Pain or swelling of the abdomen Stools that are smaller in size than normal Fever Your healthcare provider may give you other instructions, depending on your situation.
|
[
"See related health topics and resources<< Back to Gastroenterology Tests and Procedures (Cine esophagram, swallowing study, Esophagography)What is a barium swallow?",
"A barium swallow is an imaging test that uses X-rays to look at your upper gastrointestinal (GI) tract.",
"Your upper GI tract includes the back of your mouth and throat (pharynx) and your esophagus.",
"You may have just a barium swallow.",
"Or this test may be done as part of an upper GI series.",
"This series looks at your esophagus, stomach, and the first part of the small intestine (duodenum).",
"X-rays use a small amount of radiation to create images of your bones and internal organs.",
"X-rays are most often used to find bone or joint problems, or to check the heart and lungs.",
"A barium swallow is one type of X-ray.",
"Fluoroscopy is often used during a barium swallow.",
"Fluoroscopy is a kind of X-ray “movie.”The test also uses barium.",
"Barium is a substance that makes certain area of the body show up more clearly on an X-ray.",
"The radiologist will be able to see size and shape of the pharynx and esophagus.",
"He or she will also be able see how you swallow.",
"These details might not be seen on a standard X-ray.",
"Barium is used only for imaging tests for the GI tract.",
"Why might I need a barium swallow?",
"A barium swallow may be done to look for and diagnose problems in the pharynx and esophagus.",
"You may need a barium swallow if your healthcare provider think that you have: Cancer of the head and neck, pharynx, or esophagus Hiatal hernia.",
"This means that your stomach has moved up into or alongside the esophagus.",
"Structural problems, such as pouches (diverticula), narrowing (strictures), or growths (polyps)Enlarged veins (esophageal varices)Muscle disorders, such as difficulty swallowing ( dysphagia) or spasms Achalasia.",
"This is a condition in which the lower esophageal sphincter muscle doesn't relax and allow food to pass into the stomach.",
"Gastroesophageal reflux disease (GERD) and ulcers Your healthcare provider may have other reasons to recommend a barium swallow.",
"More Information About Digestive Health from Johns Hopkins Medicine Motility Mysteries: Solved!Digestive problems can be maddeningly hard to pin down.",
"Often, symptoms that manifest as gut troubles are actually signs of illness somewhere else.",
"Explore four complex cases that stumped some of the country's leading GI experts.",
"Read more.",
"What are the risks of a barium swallow?",
"You may want to ask your healthcare provider about the amount of radiation used during the test.",
"Also ask about the risks as they apply to you.",
"Consider writing down all X-rays you get, including past scans and X-rays for other health reasons.",
"Show this list to your provider.",
"The risks of radiation exposure may be tied to the number of X-rays you have and the X-ray treatments you have over time.",
"Tell your provider if: You are pregnant or think you may be pregnant.",
"Radiation exposure during pregnancy may lead to birth defects.",
"You are allergic to or sensitive to medicines, contrast dyes, local anesthesia, iodine, or latex You may have constipation or impacted stool after the test if all of the barium does not pass out of your body.",
"You should not have a barium swallow if you have: A tear or hole in your esophagus or intestines (perforation)Blockage in your intestines or severe constipation Severe problems with swallowing.",
"This makes it more likely that barium would accidentally go into your lungs (aspiration).",
"You should also not have this test if you are pregnant.",
"You may have other risks depending on your specific health condition.",
"Be sure to talk with your provider about any concerns you have before the procedure.",
"More Information About Gastrointestinal Diagnostic Exams in the Health Library Abdominal Ultrasound Abdominal X-ray Barium Enema CT Scan of the Abdomen Fluoroscopy Procedure How do I get ready for a barium swallow?",
"Your healthcare provider will explain the procedure to you.",
"Ask him or her any questions you have about the procedure.",
"You may be asked to sign a consent form that gives permission to do the procedure.",
"Read the form carefully and ask questions if anything is not clear.",
"You will need to stop eating and drinking for about 8 hours before the test.",
"Generally, this means after midnight.",
"Tell your provider if you are pregnant or think you may be pregnant.",
"Tell your provider if you are sensitive to or are allergic to any medicines, latex, tape, or anesthetic medicines (local and general).",
"Tell your provider about all medicines you are taking.",
"This includes prescriptions, over-the-counter medicines, and herbal supplements.",
"You may need to stop taking these before the test.",
"Tell your healthcare provider if you have had a recent barium swallow or upper GI test.",
"This may make it harder to get good X-rays of the lower GI area.",
"Follow any other instructions your provider gives you to get ready.",
"What happens during a barium swallow?",
"You may have a barium swallow as an outpatient or as part of your stay in a hospital.",
"The way the test is done may vary depending on your condition and your healthcare provider's practices.",
"Generally, a barium swallow follows this process: You'll be asked to remove any clothing, jewelry, or other objects that may get in the way of the test.",
"You may be asked to remove clothing.",
"If so, you will be given a gown to wear.",
"You will lie on an X-ray table that can move you from a horizontal to an upright position.",
"You may also be asked to change positions during the test.",
"For example, you may need to lie on your side, back, or stomach.",
"The radiologist may take X-rays of your chest and belly (abdomen) first.",
"The radiologist will ask you to take a swallow of a thick, chalky barium drink.",
"The barium is usually flavored, but it may not taste very good.",
"As you swallow the barium, the radiologist will take single pictures, a series of X-rays, or fluoroscopy to watch the barium moving through your mouth and throat.",
"You may be asked to hold your breath at certain times during the test.",
"You will be given a thinner barium drink to swallow.",
"The radiologist will use X-rays or fluoroscopy to watch the barium go down your esophagus.",
"You may also be asked to swallow a barium tablet.",
"This is a small pill that can help to show certain problems in the esophagus.",
"Once the radiologist has taken all of the X-rays, you'll be helped from the table.",
"What happens after a barium swallow?",
"You may go back to your normal diet and activities after a barium swallow, unless your healthcare provider tells you otherwise.",
"Barium may cause constipation or impacted stool after the procedure if it isn't completely cleared from your body.",
"You may be told to drink plenty of fluids and eat foods high in fiber to help the rest of the barium leave your body.",
"You may also be given a laxative to help with this.",
"Your bowel movements may be white or lighter in color until all the barium has left your body.",
"Call your healthcare provider right away if any of these happen: Trouble with bowel movements or you are unable to have a bowel movement or pass gas Pain or swelling of the abdomen Stools that are smaller in size than normal Fever Your healthcare provider may give you other instructions, depending on your situation."
] |
D2231850
|
https://www.thrillist.com/vice/facts-trivia-history-of-long-island-iced-tea
|
The Short And Sweet History Of The Long Island Iced Tea
|
"Lifestyle The Short And Sweet History Of The Long Island Iced Tea By Jeremy Glass Published On 04/29/2015@candyandpizza Guidecucina Remember your first Long Island Iced Tea? Of course you don't. It's hard to believe that a drink so synonymous with mind-numbing headaches has continually been ordered for almost a century. This legendary drink, while seemingly simplistic in nature, is actually drenched in more mystery than those who consume it are drenched in vomit. Recommended Video Lifestyle France's Fête des Lumières Is a Light Festival Unlike Anything You've Ever Seen Watch More LIFEOur story starts in the 1920s—when the jazz was hot, the racial intolerance was hotter, and the prohibition was raging. It was during this tumultuous time that a drink called the ""Old Man Bishop"" was concocted in a local community named Long Island in Kingsport, Tennessee by a man named—wait for it—Old Man Bishop. Legend has it that Bishop threw together a drink using rum, vodka, whiskey, gin, tequila, and maple syrup. Not unlikely during a time where booze was scarce and drinks needed to pack a punch. The ""Old Man Bishop"" was then refined and further doled out by his son, Ransom Bishop. True? Maybe. Awesome names? Hell yes!Amazon Fast-forward to the 1960s, where the love was free, the rock was hard, and Vietnam was slowly becoming more than a ""must-visit vacation spot."" This is the first time a recipe for the Long Island Iced Tea is mentioned in literature— Betty Crocker's New Picture Cook Book in 1961 — and again in the American Home All-Purpose Cookbook by Virginia T. Habeeb in 1966. A refined version of the original recipe can still be found on their website —a useful piece of information, but also a key player in the ensuing controversy surrounding this drink. Ytimg Meet Robert ""Rosebud"" Butt—Bob Butt. The most controversial figure in Long Island Iced Tea history. If you don't believe me, go to his website . While he acknowledges that, ""Possibly similar concoctions were created elsewhere, at another time,"" Butt firmly believes he invented the Long Island Iced Tea during a cocktail creating contest:"" The world famous Long Island Iced Tea was first invented in 1972 by me, Robert Butt, while I was tending bar at the infamous Oak Beach Inn. I participated in a cocktail creating contest. Triple Sec had to be included, and the bottles started flying. My concoction was an immediate hit and quickly became the house drink at the Oak Beach Inn. By the mid-1970s, every bar on Long Island was serving up this innocent-looking cocktail, and by the 1980s it was known the world over . ""Butt calls out the original ""Old Man Bishop,"" saying it's flagrantly false, and never even mentions the Betty Crocker book. Foodnetwork So what's the verdict? As is the case with most high-caliber mysteries—O. J. Simpson for example—some stories don't have a clear ending. Who created the Long Island Iced Tea? Why didn't that black glove fit? The world will never know, but both will likely kill ya. Drink on, friends. Cheers. Jeremy Glass is the Vice editor for Supercompressor and is still making O. J. Simpson jokes after all these years. Our best stories, delivered daily The best decision you'll make all day. GOI confirm I am at least 21 years old Read the Comments Trending Actually Cool Things to Do When Someone Visits Pittsburgh Everything You Should Absolutely Do in Pittsburgh This Spring The 5 New Songs You Need to Hear Right Now Krispy Kreme Is Unleashing New Nutter Butter and Chips Ahoy! Donuts Stuff You'll Like Walmart Is Hosting a Live Concert for the Viral Yodeling Boy Everyone Is Getting Free Ben & Jerry's Ice Cream Today'Killing Eve' Finally Gives 2 Women a Batman-Joker Relationship "
|
[
"\"Lifestyle The Short And Sweet History Of The Long Island Iced Tea By Jeremy Glass Published On 04/29/2015@candyandpizza Guidecucina Remember your first Long Island Iced Tea?",
"Of course you don't.",
"It's hard to believe that a drink so synonymous with mind-numbing headaches has continually been ordered for almost a century.",
"This legendary drink, while seemingly simplistic in nature, is actually drenched in more mystery than those who consume it are drenched in vomit.",
"Recommended Video Lifestyle France's Fête des Lumières Is a Light Festival Unlike Anything You've Ever Seen Watch More LIFEOur story starts in the 1920s—when the jazz was hot, the racial intolerance was hotter, and the prohibition was raging.",
"It was during this tumultuous time that a drink called the \"\"Old Man Bishop\"\" was concocted in a local community named Long Island in Kingsport, Tennessee by a man named—wait for it—Old Man Bishop.",
"Legend has it that Bishop threw together a drink using rum, vodka, whiskey, gin, tequila, and maple syrup.",
"Not unlikely during a time where booze was scarce and drinks needed to pack a punch.",
"The \"\"Old Man Bishop\"\" was then refined and further doled out by his son, Ransom Bishop.",
"True?",
"Maybe.",
"Awesome names?",
"Hell yes!Amazon Fast-forward to the 1960s, where the love was free, the rock was hard, and Vietnam was slowly becoming more than a \"\"must-visit vacation spot.\"\"",
"This is the first time a recipe for the Long Island Iced Tea is mentioned in literature— Betty Crocker's New Picture Cook Book in 1961 — and again in the American Home All-Purpose Cookbook by Virginia T. Habeeb in 1966.",
"A refined version of the original recipe can still be found on their website —a useful piece of information, but also a key player in the ensuing controversy surrounding this drink.",
"Ytimg Meet Robert \"\"Rosebud\"\" Butt—Bob Butt.",
"The most controversial figure in Long Island Iced Tea history.",
"If you don't believe me, go to his website .",
"While he acknowledges that, \"\"Possibly similar concoctions were created elsewhere, at another time,\"\" Butt firmly believes he invented the Long Island Iced Tea during a cocktail creating contest:\"\" The world famous Long Island Iced Tea was first invented in 1972 by me, Robert Butt, while I was tending bar at the infamous Oak Beach Inn.",
"I participated in a cocktail creating contest.",
"Triple Sec had to be included, and the bottles started flying.",
"My concoction was an immediate hit and quickly became the house drink at the Oak Beach Inn.",
"By the mid-1970s, every bar on Long Island was serving up this innocent-looking cocktail, and by the 1980s it was known the world over .",
"\"\"Butt calls out the original \"\"Old Man Bishop,\"\" saying it's flagrantly false, and never even mentions the Betty Crocker book.",
"Foodnetwork So what's the verdict?",
"As is the case with most high-caliber mysteries—O.",
"J. Simpson for example—some stories don't have a clear ending.",
"Who created the Long Island Iced Tea?",
"Why didn't that black glove fit?",
"The world will never know, but both will likely kill ya.",
"Drink on, friends.",
"Cheers.",
"Jeremy Glass is the Vice editor for Supercompressor and is still making O. J. Simpson jokes after all these years.",
"Our best stories, delivered daily The best decision you'll make all day.",
"GOI confirm I am at least 21 years old Read the Comments Trending Actually Cool Things to Do When Someone Visits Pittsburgh Everything You Should Absolutely Do in Pittsburgh This Spring The 5 New Songs You Need to Hear Right Now Krispy Kreme Is Unleashing New Nutter Butter and Chips Ahoy!",
"Donuts Stuff You'll Like Walmart Is Hosting a Live Concert for the Viral Yodeling Boy Everyone Is Getting Free Ben & Jerry's Ice Cream Today'Killing Eve' Finally Gives 2 Women a Batman-Joker Relationship \""
] |
D871791
|
https://learn.org/articles/How_Can_I_Become_a_Histologist.html
|
How Can I Become a Histologist?
|
How Can I Become a Histologist? Research what it takes to become a histologist. Learn about education and certification options, job outlook and salary information to find out if this is the career for you. Schools offering Clinical Laboratory Science degrees can also be found in these popular choices . What Is a Histologist? A histologist is a medical laboratory technologist who specializes in preparing tissue samples for medical purposes or research studies. They cut samples and treat them with staining chemicals so that they are ready for analysis by pathologists, who can use them for diagnostic purposes or to conduct academic research that advances the medical community's understanding of the causes and development of a particular disease. Additionally, histologists may serve as supervisors for lower-level workers in the lab, such as histotechnicians. The table below provides an overview for this career: Education Required Certificate, associate's degree or bachelor's degree Education Field of Study Histotechnology, medical lab technology, chemistry, biology Key Responsibilities Prepare tissue for study, examine samples, utilize lab instruments Licensure/Certification Voluntary certification available; license requirements vary by state Job Growth (2014-24) 14%* (medical and clinical laboratory technologists)Median Salary (2017) $52,901**Source: *U. S. Bureau of Labor Statistics, **Payscale.com What Would I Do as a Histologist? The term histologist includes both histotechnicians and histotechnologists. Histologists are laboratory staff members who work with cells and tissues from human beings, animals and plants. As a histologist, you prepare tissues that are then studied under a microscope by pathologists to discover irregularities or diseases. You place tissue samples on glass slides and apply stain to make the cells identifiable with a microscope. You examine the samples under a microscope to check that the tissues were prepared according to lab guidelines. You also use lab instruments to dry, freeze or otherwise prepare tissue samples. According to the National Society for Histotechnology (NSH), histotechnologists perform more specialized tasks than histotechnicians, such as electron microscopy and enzyme histochemistry ( www.nsh.org ). Histotechnologists may supervise at labs and are qualified to teach or work as school directors, according to the NSH. What Education Should I Obtain? The American Society for Clinical Pathology's Board of Certification oversees certification tests for both histotechnicians and histotechnologists. You do not need certification for employment as a histologist, but it is highly recommended. To be eligible for certification as a histotechnician, you must complete a histotechnician program accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS). Alternatively, you can earn a minimum of 60 semester hours, with a combined total of 12 hours in chemistry and biology, at an accredited college or university plus have a year of eligible experience in a histopathology lab. Or you can earn an associate's degree, including a combined total of 12 semester hours in chemistry and biology, from an accredited school plus have a year of eligible experience in a histopathology lab. For certification as a histotechnologist, you must earn a bachelor's degree from an accredited school with a combined total of 30 semester hours in chemistry and biology. In addition to the undergraduate degree, you must complete a histology program accredited by the NAACLS or have a year of eligible experience at a histopathology lab. The states have varying license requirements for histologists. What Could I Earn as a Histologist? As of January 2017, the lowest-paid 10% of histologists earned $38,285 or less per year, Pay Scale.com reported. The highest-paid 10% of histologists earned $68,962 or more per year. What Are Some Related Alternative Careers? Not all medical laboratory technologists choose to specialize; you could also work as a generalist, where you would be involved in diagnostic experiments in many different areas, not just histology. You could also specialize in a different subfield. For instance, cytotechnologists focus on the preparation and analysis of cells, while molecular biology technologists are experts in tests on proteins and nucleic acids. Outside of the medical field, you could also look at a job as forensic science technician in a laboratory setting. These professionals contribute to criminal investigations by running experiments on chemical and biological samples. To get any of these jobs, you will need at least a bachelor's degree. To continue researching, browse degree options below for course curriculum, prerequisites and financial aid information. Or, learn more about the subject by reading the related articles below:1. Degree Options: Clinical Laboratory Science Clinical Research Administration Allied Health View All Degree Options2. More Articles How Do Short Medical Courses Work? Which Medical Schools are Located in Missouri? What Are the Largest Pennsylvania Medical Schools?
|
[
"How Can I Become a Histologist?",
"Research what it takes to become a histologist.",
"Learn about education and certification options, job outlook and salary information to find out if this is the career for you.",
"Schools offering Clinical Laboratory Science degrees can also be found in these popular choices .",
"What Is a Histologist?",
"A histologist is a medical laboratory technologist who specializes in preparing tissue samples for medical purposes or research studies.",
"They cut samples and treat them with staining chemicals so that they are ready for analysis by pathologists, who can use them for diagnostic purposes or to conduct academic research that advances the medical community's understanding of the causes and development of a particular disease.",
"Additionally, histologists may serve as supervisors for lower-level workers in the lab, such as histotechnicians.",
"The table below provides an overview for this career: Education Required Certificate, associate's degree or bachelor's degree Education Field of Study Histotechnology, medical lab technology, chemistry, biology Key Responsibilities Prepare tissue for study, examine samples, utilize lab instruments Licensure/Certification Voluntary certification available; license requirements vary by state Job Growth (2014-24) 14%* (medical and clinical laboratory technologists)Median Salary (2017) $52,901**Source: *U. S. Bureau of Labor Statistics, **Payscale.com What Would I Do as a Histologist?",
"The term histologist includes both histotechnicians and histotechnologists.",
"Histologists are laboratory staff members who work with cells and tissues from human beings, animals and plants.",
"As a histologist, you prepare tissues that are then studied under a microscope by pathologists to discover irregularities or diseases.",
"You place tissue samples on glass slides and apply stain to make the cells identifiable with a microscope.",
"You examine the samples under a microscope to check that the tissues were prepared according to lab guidelines.",
"You also use lab instruments to dry, freeze or otherwise prepare tissue samples.",
"According to the National Society for Histotechnology (NSH), histotechnologists perform more specialized tasks than histotechnicians, such as electron microscopy and enzyme histochemistry ( www.nsh.org ).",
"Histotechnologists may supervise at labs and are qualified to teach or work as school directors, according to the NSH.",
"What Education Should I Obtain?",
"The American Society for Clinical Pathology's Board of Certification oversees certification tests for both histotechnicians and histotechnologists.",
"You do not need certification for employment as a histologist, but it is highly recommended.",
"To be eligible for certification as a histotechnician, you must complete a histotechnician program accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS).",
"Alternatively, you can earn a minimum of 60 semester hours, with a combined total of 12 hours in chemistry and biology, at an accredited college or university plus have a year of eligible experience in a histopathology lab.",
"Or you can earn an associate's degree, including a combined total of 12 semester hours in chemistry and biology, from an accredited school plus have a year of eligible experience in a histopathology lab.",
"For certification as a histotechnologist, you must earn a bachelor's degree from an accredited school with a combined total of 30 semester hours in chemistry and biology.",
"In addition to the undergraduate degree, you must complete a histology program accredited by the NAACLS or have a year of eligible experience at a histopathology lab.",
"The states have varying license requirements for histologists.",
"What Could I Earn as a Histologist?",
"As of January 2017, the lowest-paid 10% of histologists earned $38,285 or less per year, Pay Scale.com reported.",
"The highest-paid 10% of histologists earned $68,962 or more per year.",
"What Are Some Related Alternative Careers?",
"Not all medical laboratory technologists choose to specialize; you could also work as a generalist, where you would be involved in diagnostic experiments in many different areas, not just histology.",
"You could also specialize in a different subfield.",
"For instance, cytotechnologists focus on the preparation and analysis of cells, while molecular biology technologists are experts in tests on proteins and nucleic acids.",
"Outside of the medical field, you could also look at a job as forensic science technician in a laboratory setting.",
"These professionals contribute to criminal investigations by running experiments on chemical and biological samples.",
"To get any of these jobs, you will need at least a bachelor's degree.",
"To continue researching, browse degree options below for course curriculum, prerequisites and financial aid information.",
"Or, learn more about the subject by reading the related articles below:1.",
"Degree Options: Clinical Laboratory Science Clinical Research Administration Allied Health View All Degree Options2.",
"More Articles How Do Short Medical Courses Work?",
"Which Medical Schools are Located in Missouri?",
"What Are the Largest Pennsylvania Medical Schools?"
] |
D1088260
|
http://beef2live.com/story-world-beef-imports-ranking-countries-0-106900
|
World Beef Imports: Ranking Of Countries
|
World Beef Imports: Ranking Of Countries The United States is the largest beef importer in the world in 2016 followed by China & Japan. Rob Cook| Published on: Apr 8, 2018Tweet United States remains world's largest beef importer The United States was the largest beef importer in the world in 2016 followed by China & Japan. The United States, China & Japan account for nearly 38% of the world's beef imports. The United States imported more beef in 2016 than Japan and South Korea COMBINED. Related Stories: Beef Talk: A Beef Cow is What She Eats Beef Talk: Grazing Systems Combine MLRAs and Ecological Sites Calf Prices By Year
|
[
"World Beef Imports: Ranking Of Countries The United States is the largest beef importer in the world in 2016 followed by China & Japan.",
"Rob Cook| Published on: Apr 8, 2018Tweet United States remains world's largest beef importer The United States was the largest beef importer in the world in 2016 followed by China & Japan.",
"The United States, China & Japan account for nearly 38% of the world's beef imports.",
"The United States imported more beef in 2016 than Japan and South Korea COMBINED.",
"Related Stories: Beef Talk: A Beef Cow is What She Eats Beef Talk: Grazing Systems Combine MLRAs and Ecological Sites Calf Prices By Year"
] |
D319128
|
http://physics.tutorvista.com/waves/wave-speed.html
|
Wave Speed
|
Physics Waves Wave Speed Wave Speed A wave is defined as a disturbance which is moved medium; for example, the wave of the ocean moves in medium water and we can see the movement of wave crest from one side to the other side in a given time period. The motion of objects is described in terms of speed which shows the fastness of the object. Speed is the covered distance per units of time. The general mathematical formula of speed is distance divided by time; for example, if a crest of wave is covered distance of 30 meter in 10 sec then the sped of wave is 3 m per sec but if other crest covered 35 meter in 10sec then its speed is 3.5 m/s. Thus, we can see that fast wave is covered long distance in the same time period. We know that frequency of wave is the number count of waves in the gives point of time. It also affects the speed of wave. Let’s discuss wave speed examples and how frequency can affects the speed of wave. As with the particle the waves too have speed. If we observe the sea waves we see that the crests and troughs travel the distance from one point of another. Sometimes, they travel faster which means that the wave reaches to the shore quickly while other time it is too slow to reach the shores. Wave Speed Definition Back to Top The wave speed is measured as the distance travelled by the crests or trough in a given time interval. The relationship is similar to the relationship of speed, distance and time in the classical physics.== speed of the wave = distance travelled by crest or trough of the wave T = time taken to travel the distance This equation is the speed of any particle according to the classical theory of physics and it is equally applicable to the waves due to their dual nature. Wave Speed Formula Back to Top As we know that the distance travelled by the wave can be obtained in terms of its wavelength and hence we can say that the distance travelled by the wave is equal to the number of wave length (?) it covers and the inverse of the time is taken to be the frequency (f) then the above equation can be rewritten as;=This equation is known as Wave Speed Formula or Wave Speed Equation. T ake an example to understand the wave speed better. You are at the peak of a mountain and you shout loudly your name facing the valley. The valley between the peak of mountains is 175 meters deep. After around 1 sec you hear your echo. Would you be able to tell the speed of the sound. The answer is 350 m/sec. I know you are surprised now that how is it possible. The answer to this question is for finding the speed of the sound waves we need to calculate total distance traveled by the sound waves before you hear back your echo. That distance is two times the distance from peak of mountain to the valley and hence the speed is 350 m/sec. Does Frequency Affect Wave Speed? Back to Top The speed of the wave is not affect by its wavelength and its frequency. Rather the speed of wave is not affected by the characteristics of the wave but by the characteristics of the medium in which it is traveling. So, the answer to an obvious question “ Does Frequency Affect Wave Speed “ is that the wave speed is not affected by the frequency of the wave. For a sound wave the denser the medium the faster the wave will travels, while the light travels at slow speed in the denser medium. Factors Affecting Wave Speed We know that each particle vibrate in a medium by itself. The phenomenon of wave is produced by the fact that each and every particle in the medium is connected to its neighbor (s) by some bond, like elastic forces. The speed of the wave through the medium is determined by a competition between two factors: The elasticity factor : In the medium with high density, the particles are bonded more closely and hence the wave travels at the faster rate in these mediums. The inertia factor : When the density is high it is very difficult to avoid the effect of inertia between the particles and hence they compromised the speed gains due to the denser medium. The speed of wave is the trade off between these two factors of the medium in which wave is traveling. For example, the equation for speed of the wave in a stretched string is:= where, = tension force = linear mass density. Electromagnetic Wave Speed Back to Top The electromagnetic waves by nature have speed equal to thespeed of the light i.e m/s. Depending upon the medium the speed may vary but the variation is very less in comparison to their high magnitude. Since the radio waves also comes in the category of the electromagnetic wave and hence Radio Wave Speed is also equivalent to the speed of light. Wave Propagation Speed Back to Top The wave propagation speed is the speed by which the wavefront of the wave passes through a medium. The wavefront is the locus of the same phase point in the wave. It is also known as Velocity factor (VF). The velocity factor has different equation for different medium. In optical fiber it is the reciprocal of the refractive index of the medium. It is also equal to the square root of the dielectric constant of the material. Velocity factor = Velocity factor = where, k = dielectric constant of the medium c = speed of light L = inductance C = capacitance There are few other types of velocities associated with the wave, namely:1. Group Velocity: It is the velocity with which the amplitude of the wave travels in the medium. It is given by the formula;=So, it can also be defined as the rate of change of the angular frequency of the wave with respect to the angular wave number of the wave.2. Phase Velocity: It is the velocity with which one of the phase of the wave travels in the medium. It is given by the formula;= = = =Where,v P = phase velocity; ? = angular frequency; k = wave number. Calculating Wave Speed Back to Top Let us find the methods by which we can calculate wave speed. Solved Examples Question 1: Calculate the velocity of a water wave if the frequency is 400 Hz, the wavelength is 6 m, and the amplitude of the wave is 3.76 cm. Solution: We know that the distance travelled by the wave in one complete cycle is 6 m and it completes 400 cycles per second, so the velocity of the wave is given by;V = 400 6V = 2400 m/sec;V = 2.4 Km/sec. Question 2: A sound wave is travelling with a speed of 343 m/s, calculate its frequency if the wavelength of the wave is 500m. Solution: We know that the speed of the wave is related to the frequency and wavelength as;==So,== 0.686 per sec So the frequency of the sound wave is 0.686 cycle per second which means that it is covering only 0.686 of its wavelength in one second. Amplitude of a Wave Wavelength Related Topics Physics Help Physics Tutor
|
[
"Physics Waves Wave Speed Wave Speed A wave is defined as a disturbance which is moved medium; for example, the wave of the ocean moves in medium water and we can see the movement of wave crest from one side to the other side in a given time period.",
"The motion of objects is described in terms of speed which shows the fastness of the object.",
"Speed is the covered distance per units of time.",
"The general mathematical formula of speed is distance divided by time; for example, if a crest of wave is covered distance of 30 meter in 10 sec then the sped of wave is 3 m per sec but if other crest covered 35 meter in 10sec then its speed is 3.5 m/s.",
"Thus, we can see that fast wave is covered long distance in the same time period.",
"We know that frequency of wave is the number count of waves in the gives point of time.",
"It also affects the speed of wave.",
"Let’s discuss wave speed examples and how frequency can affects the speed of wave.",
"As with the particle the waves too have speed.",
"If we observe the sea waves we see that the crests and troughs travel the distance from one point of another.",
"Sometimes, they travel faster which means that the wave reaches to the shore quickly while other time it is too slow to reach the shores.",
"Wave Speed Definition Back to Top The wave speed is measured as the distance travelled by the crests or trough in a given time interval.",
"The relationship is similar to the relationship of speed, distance and time in the classical physics.== speed of the wave = distance travelled by crest or trough of the wave T = time taken to travel the distance This equation is the speed of any particle according to the classical theory of physics and it is equally applicable to the waves due to their dual nature.",
"Wave Speed Formula Back to Top As we know that the distance travelled by the wave can be obtained in terms of its wavelength and hence we can say that the distance travelled by the wave is equal to the number of wave length (?)",
"it covers and the inverse of the time is taken to be the frequency (f) then the above equation can be rewritten as;=This equation is known as Wave Speed Formula or Wave Speed Equation.",
"T ake an example to understand the wave speed better.",
"You are at the peak of a mountain and you shout loudly your name facing the valley.",
"The valley between the peak of mountains is 175 meters deep.",
"After around 1 sec you hear your echo.",
"Would you be able to tell the speed of the sound.",
"The answer is 350 m/sec.",
"I know you are surprised now that how is it possible.",
"The answer to this question is for finding the speed of the sound waves we need to calculate total distance traveled by the sound waves before you hear back your echo.",
"That distance is two times the distance from peak of mountain to the valley and hence the speed is 350 m/sec.",
"Does Frequency Affect Wave Speed?",
"Back to Top The speed of the wave is not affect by its wavelength and its frequency.",
"Rather the speed of wave is not affected by the characteristics of the wave but by the characteristics of the medium in which it is traveling.",
"So, the answer to an obvious question “ Does Frequency Affect Wave Speed “ is that the wave speed is not affected by the frequency of the wave.",
"For a sound wave the denser the medium the faster the wave will travels, while the light travels at slow speed in the denser medium.",
"Factors Affecting Wave Speed We know that each particle vibrate in a medium by itself.",
"The phenomenon of wave is produced by the fact that each and every particle in the medium is connected to its neighbor (s) by some bond, like elastic forces.",
"The speed of the wave through the medium is determined by a competition between two factors: The elasticity factor : In the medium with high density, the particles are bonded more closely and hence the wave travels at the faster rate in these mediums.",
"The inertia factor : When the density is high it is very difficult to avoid the effect of inertia between the particles and hence they compromised the speed gains due to the denser medium.",
"The speed of wave is the trade off between these two factors of the medium in which wave is traveling.",
"For example, the equation for speed of the wave in a stretched string is:= where, = tension force = linear mass density.",
"Electromagnetic Wave Speed Back to Top The electromagnetic waves by nature have speed equal to thespeed of the light i.e m/s.",
"Depending upon the medium the speed may vary but the variation is very less in comparison to their high magnitude.",
"Since the radio waves also comes in the category of the electromagnetic wave and hence Radio Wave Speed is also equivalent to the speed of light.",
"Wave Propagation Speed Back to Top The wave propagation speed is the speed by which the wavefront of the wave passes through a medium.",
"The wavefront is the locus of the same phase point in the wave.",
"It is also known as Velocity factor (VF).",
"The velocity factor has different equation for different medium.",
"In optical fiber it is the reciprocal of the refractive index of the medium.",
"It is also equal to the square root of the dielectric constant of the material.",
"Velocity factor = Velocity factor = where, k = dielectric constant of the medium c = speed of light L = inductance C = capacitance There are few other types of velocities associated with the wave, namely:1.",
"Group Velocity: It is the velocity with which the amplitude of the wave travels in the medium.",
"It is given by the formula;=So, it can also be defined as the rate of change of the angular frequency of the wave with respect to the angular wave number of the wave.2.",
"Phase Velocity: It is the velocity with which one of the phase of the wave travels in the medium.",
"It is given by the formula;= = = =Where,v P = phase velocity; ?",
"= angular frequency; k = wave number.",
"Calculating Wave Speed Back to Top Let us find the methods by which we can calculate wave speed.",
"Solved Examples Question 1: Calculate the velocity of a water wave if the frequency is 400 Hz, the wavelength is 6 m, and the amplitude of the wave is 3.76 cm.",
"Solution: We know that the distance travelled by the wave in one complete cycle is 6 m and it completes 400 cycles per second, so the velocity of the wave is given by;V = 400 6V = 2400 m/sec;V = 2.4 Km/sec.",
"Question 2: A sound wave is travelling with a speed of 343 m/s, calculate its frequency if the wavelength of the wave is 500m.",
"Solution: We know that the speed of the wave is related to the frequency and wavelength as;==So,== 0.686 per sec So the frequency of the sound wave is 0.686 cycle per second which means that it is covering only 0.686 of its wavelength in one second.",
"Amplitude of a Wave Wavelength Related Topics Physics Help Physics Tutor"
] |
D3221007
|
https://www.g2crowd.com/categories/integrated-development-environment-ide
|
Best Integrated Development Environment (IDE) Software
|
Best Integrated Development Environment (IDE) Software IDE Definition: Integrated development environments, or IDEs, are software platforms that provide programmers and developers a comprehensive set of tools for software development in a single product. IDEs are built to work with specific application platforms and remove barriers involved in the lifecycle of software development. IDEs are used in development teams to build new software, apps, web pages, and services, and they help by providing one tool with all the features and removing the need for integrations. IDEs are for programming code to a specific platform or platforms, and have integrated features that know how the platform works and how to use the features of the platform through compiling code, debugging code, or intelligently completing code automatically. To qualify for inclusion in the Integrated Development Environment category, a product must: Provide programming capabilities through a text editor or a GUI (graphical user interface)Integrate with at least one platform without a separate plugin Expose a platform’s application programming interface (API) and allow for compiling, debugging, version control, platform-specific code suggestions, or code deployment Integrated Development Environment (IDE) Software Grid ® Overview The best Integrated Development Environment (IDE) Software products are determined by customer satisfaction (based on user reviews) and scale (based on market share, vendor size, and social impact) and placed into four categories on the Grid ®: Products in the Leader quadrant are rated highly by G2 Crowd users and have substantial Market Presence scores. Leaders include: Net Beans, Visual Studio, Adobe Flash Builder, Eclipse, Intelli J IDEA, Web Storm, Xcode, Py Charm, Php Storm, and Arduino IDEHigh Performers are highly rated by their users, but have not yet achieved the market share and scale of the Leaders. High Performers include: Ruby Mine, Blue J, Flashdevelop, My Eclipse, CLion, Visual LANSA, and Data Grip Contenders have significant Market Presence and resources, but have received below average user Satisfaction ratings or have not yet received a sufficient number of reviews to validate the solution. Contenders include: Oracle JDeveloper and Cold Fusion Builder Niche solutions do not have the Market Presence of the Leaders. They may have been rated positively on customer Satisfaction, but have not yet received enough reviews to validate them. Niche products include: Komodo IDE, Aptana Studio, Code:: Blocks, Codenvy, Monodevelop, Rational Application Developer for Web Sphere Software, Selenium IDE, Nuclide, and Qt Creatorshow more G2 Crowd Grid ® for IDEAll Small-Business Mid-Market Enterprise Leaders High Performers Contenders Niche Market Presence Satisfaction Grid ® Scoring
|
[
"Best Integrated Development Environment (IDE) Software IDE Definition: Integrated development environments, or IDEs, are software platforms that provide programmers and developers a comprehensive set of tools for software development in a single product.",
"IDEs are built to work with specific application platforms and remove barriers involved in the lifecycle of software development.",
"IDEs are used in development teams to build new software, apps, web pages, and services, and they help by providing one tool with all the features and removing the need for integrations.",
"IDEs are for programming code to a specific platform or platforms, and have integrated features that know how the platform works and how to use the features of the platform through compiling code, debugging code, or intelligently completing code automatically.",
"To qualify for inclusion in the Integrated Development Environment category, a product must: Provide programming capabilities through a text editor or a GUI (graphical user interface)Integrate with at least one platform without a separate plugin Expose a platform’s application programming interface (API) and allow for compiling, debugging, version control, platform-specific code suggestions, or code deployment Integrated Development Environment (IDE) Software Grid ® Overview The best Integrated Development Environment (IDE) Software products are determined by customer satisfaction (based on user reviews) and scale (based on market share, vendor size, and social impact) and placed into four categories on the Grid ®: Products in the Leader quadrant are rated highly by G2 Crowd users and have substantial Market Presence scores.",
"Leaders include: Net Beans, Visual Studio, Adobe Flash Builder, Eclipse, Intelli J IDEA, Web Storm, Xcode, Py Charm, Php Storm, and Arduino IDEHigh Performers are highly rated by their users, but have not yet achieved the market share and scale of the Leaders.",
"High Performers include: Ruby Mine, Blue J, Flashdevelop, My Eclipse, CLion, Visual LANSA, and Data Grip Contenders have significant Market Presence and resources, but have received below average user Satisfaction ratings or have not yet received a sufficient number of reviews to validate the solution.",
"Contenders include: Oracle JDeveloper and Cold Fusion Builder Niche solutions do not have the Market Presence of the Leaders.",
"They may have been rated positively on customer Satisfaction, but have not yet received enough reviews to validate them.",
"Niche products include: Komodo IDE, Aptana Studio, Code:: Blocks, Codenvy, Monodevelop, Rational Application Developer for Web Sphere Software, Selenium IDE, Nuclide, and Qt Creatorshow more G2 Crowd Grid ® for IDEAll Small-Business Mid-Market Enterprise Leaders High Performers Contenders Niche Market Presence Satisfaction Grid ® Scoring"
] |
D2803363
|
http://www.travelmath.com/drive-distance/from/Ancona,+Italy/to/Rome,+Italy
|
The driving distance from Ancona, Italy to Rome, Italy is:
|
The driving distance from Ancona, Italy to Rome, Italy is:193 miles /311 km City: Check-in: Check-out: Rooms: Travelers: Get: Get: From: To: Ancona to Rome road trip Map of driving directions from Ancona, Italy to Rome, Italy Click here to show map Drag the line on the map to calculate the driving distance for a different route. If you want to verify these driving directions or look for another possible route, you can try Google Maps , Bing Maps, or Map Quest. More trip calculationsdriving time from Ancona, Italy to Rome, Italycost of driving from Ancona, Italy to Rome, Italyreverse drive distance from Rome, Italy to Ancona, Italyhalfway between Ancona, Italy and Rome, Italystopping points from Ancona, Italy to Rome, Italyhotels near Rome, Italyflight distance from Ancona, Italy to Rome, Italyflight time from Ancona, Italy to Rome, Italyfly or drive from Ancona, Italy to Rome, Italyairports near Rome, Italyairlines flying to Rome, Italynonstop flights from Ancona, Italy to Rome, Italytime difference between Ancona, Italy and Rome, Italy
|
[
"The driving distance from Ancona, Italy to Rome, Italy is:193 miles /311 km City: Check-in: Check-out: Rooms: Travelers: Get: Get: From: To: Ancona to Rome road trip Map of driving directions from Ancona, Italy to Rome, Italy Click here to show map Drag the line on the map to calculate the driving distance for a different route.",
"If you want to verify these driving directions or look for another possible route, you can try Google Maps , Bing Maps, or Map Quest.",
"More trip calculationsdriving time from Ancona, Italy to Rome, Italycost of driving from Ancona, Italy to Rome, Italyreverse drive distance from Rome, Italy to Ancona, Italyhalfway between Ancona, Italy and Rome, Italystopping points from Ancona, Italy to Rome, Italyhotels near Rome, Italyflight distance from Ancona, Italy to Rome, Italyflight time from Ancona, Italy to Rome, Italyfly or drive from Ancona, Italy to Rome, Italyairports near Rome, Italyairlines flying to Rome, Italynonstop flights from Ancona, Italy to Rome, Italytime difference between Ancona, Italy and Rome, Italy"
] |
D3112790
|
https://quizlet.com/68153808/fin-310-chapter-2-flash-cards/
|
Fin 310 Chapter 2
|
12 terms ty_hentges Fin 310 Chapter 2Learn Flashcards Write Spell Test Match Gravity Advertisement Upgrade to remove ads Sortloanable funds theory theory used to explain interest rate movements, suggests that the market interest rate is determined by the factors controlling the supply of and demand for loanable funds.interest inelastic Insensitive to interest ratesforeign demand depends on interest rate differential between the two countriescrowding out effect government demand for funds crowd out private demand for fundseconomic conditions primary forces in change in supply of savingsfactors that affect interest rate movement economic growth, inflation, budget deficit, foreign interest rates, and money supply. Explain what is meant by interest elasticity. Would you expect federal government demand for loanable funds to be more or less interest-elastic than household demand for loanable funds? Why? Interest elasticity of supply represents a change in the quantity of loanable funds supplied in response to a change in interest rates. Interest elasticity of demand represents a change in the quantity of loanable funds demanded in response to a change in interest rates. Explain why interest rates tend to decrease during recessionary periods. Review historical interest rates to determine how they react to recessionary periods. Explain this reaction. During a recession, firms and consumers reduce their amount of borrowing. The demand for loanable funds decreases and interest rates decrease as a result. Should increasing money supply growth place upward or downward pressure on interest rates? If one believes that higher money supply growth will not cause inflationary expectations, the additional supply of funds places downward pressure on interest rates. However, if one believes that inflation expectations do erupt as a result, demand for loanable funds will also increase, and interest rates could increase (if the increase in demand more than offsets the increase in supply). What is the difference between the nominal interest rate and real interest rate? What is the logic behind the implied positive relationship between expected inflation and nominal interest rates? The nominal interest rate is the quoted interest rate, while the real interest rate is defined as the nominal interest rate minus the expected rate of inflation. The real interest rate represents the recent nominal interest rate minus the recent inflation rate. Investors require a positive real return, which suggests that they will only invest funds if the nominal interest rate is expected to exceed inflation. In this way, the purchasing power of invested funds increases over time. As inflation rises, nominal interest rates should rise as well since investors would require a nominal return that exceeds the inflation rate. Jayhawk Forecasting Services analyzed several factors that could affect interest rates in the future. Most factors were expected to place downward pressure on interest rates. Jayhawk also expected that although the annual budget deficit was to be cut by 40 percent from the previous year, it would still be very large. Thus, Jayhawk believed that the deficit's impact would more than offset the effects of other factors, so it forecast interest rates to increase by 2 percent. Comment on Jayhawk's logic. A reduction in the deficit should free up some funds that had been used to support the government borrowings. Thus, there should be additional funds available to satisfy other borrowing needs. Given this situation plus the other information, Jayhawk should have forecasted lower interest rates. During the credit crisis, U. S. interest rates were extremely low, which enabled businesses to borrow at a low cost. Holding other factors constant, this should result in a higher number of feasible projects, which should encourage businesses to borrow more money and expand. Yet, many businesses that had access to loanable funds were unwilling to borrow during the credit crisis. What other factor changed during this period that more than offset the potentially favorable effect of the low interest rates on project feasibility, therefore discouraging businesses from expanding? Businesses recognized that the cash flows to be generated from their projects would be low because the demand for their products and services was limited. Households could not afford to purchase more products. Thus, while low interest rates allow businesses to borrow funds cheap, many possible projects were not feasible because the expected cash flows were not sufficient.
|
[
"12 terms ty_hentges Fin 310 Chapter 2Learn Flashcards Write Spell Test Match Gravity Advertisement Upgrade to remove ads Sortloanable funds theory theory used to explain interest rate movements, suggests that the market interest rate is determined by the factors controlling the supply of and demand for loanable funds.interest inelastic Insensitive to interest ratesforeign demand depends on interest rate differential between the two countriescrowding out effect government demand for funds crowd out private demand for fundseconomic conditions primary forces in change in supply of savingsfactors that affect interest rate movement economic growth, inflation, budget deficit, foreign interest rates, and money supply.",
"Explain what is meant by interest elasticity.",
"Would you expect federal government demand for loanable funds to be more or less interest-elastic than household demand for loanable funds?",
"Why?",
"Interest elasticity of supply represents a change in the quantity of loanable funds supplied in response to a change in interest rates.",
"Interest elasticity of demand represents a change in the quantity of loanable funds demanded in response to a change in interest rates.",
"Explain why interest rates tend to decrease during recessionary periods.",
"Review historical interest rates to determine how they react to recessionary periods.",
"Explain this reaction.",
"During a recession, firms and consumers reduce their amount of borrowing.",
"The demand for loanable funds decreases and interest rates decrease as a result.",
"Should increasing money supply growth place upward or downward pressure on interest rates?",
"If one believes that higher money supply growth will not cause inflationary expectations, the additional supply of funds places downward pressure on interest rates.",
"However, if one believes that inflation expectations do erupt as a result, demand for loanable funds will also increase, and interest rates could increase (if the increase in demand more than offsets the increase in supply).",
"What is the difference between the nominal interest rate and real interest rate?",
"What is the logic behind the implied positive relationship between expected inflation and nominal interest rates?",
"The nominal interest rate is the quoted interest rate, while the real interest rate is defined as the nominal interest rate minus the expected rate of inflation.",
"The real interest rate represents the recent nominal interest rate minus the recent inflation rate.",
"Investors require a positive real return, which suggests that they will only invest funds if the nominal interest rate is expected to exceed inflation.",
"In this way, the purchasing power of invested funds increases over time.",
"As inflation rises, nominal interest rates should rise as well since investors would require a nominal return that exceeds the inflation rate.",
"Jayhawk Forecasting Services analyzed several factors that could affect interest rates in the future.",
"Most factors were expected to place downward pressure on interest rates.",
"Jayhawk also expected that although the annual budget deficit was to be cut by 40 percent from the previous year, it would still be very large.",
"Thus, Jayhawk believed that the deficit's impact would more than offset the effects of other factors, so it forecast interest rates to increase by 2 percent.",
"Comment on Jayhawk's logic.",
"A reduction in the deficit should free up some funds that had been used to support the government borrowings.",
"Thus, there should be additional funds available to satisfy other borrowing needs.",
"Given this situation plus the other information, Jayhawk should have forecasted lower interest rates.",
"During the credit crisis, U. S. interest rates were extremely low, which enabled businesses to borrow at a low cost.",
"Holding other factors constant, this should result in a higher number of feasible projects, which should encourage businesses to borrow more money and expand.",
"Yet, many businesses that had access to loanable funds were unwilling to borrow during the credit crisis.",
"What other factor changed during this period that more than offset the potentially favorable effect of the low interest rates on project feasibility, therefore discouraging businesses from expanding?",
"Businesses recognized that the cash flows to be generated from their projects would be low because the demand for their products and services was limited.",
"Households could not afford to purchase more products.",
"Thus, while low interest rates allow businesses to borrow funds cheap, many possible projects were not feasible because the expected cash flows were not sufficient."
] |
D779825
|
https://www.reference.com/history/definition-allied-powers-1cc3bec1303f0685
|
What Is the Definition of the Allied Powers?
|
"History Modern History World War 2Q: What Is the Definition of the Allied Powers? A: Quick Answer The Allied Powers, or Allies, refers to coalitions of primarily North American nations victorious over rival, central-European forces in World War I and World War II. The four nations that recurred as the main forces of the Allied Powers in both wars were France, Russia/USSR, the United Kingdom and the United States. Continue Reading Keep Learning What Were the Axis Powers? Which Countries Were the Allied Forces' Enemies During World War II? What Are the Main Countries That Made up the Allied Powers? Full Answer The antagonists of the Allied Powers in World Wars I and II were coalitions begun by Germany, the Central Powers and Axis Powers, respectively. Italy, though an Allied Power during World War I, joined the Axis Powers under the leadership of Benito Mussolini, only to depose Mussolini in 1943 and fight the German occupation of their northern territories. The inclusion of Japan into the Axis Powers made China join the Allied Powers. Otherwise, the history of formal treaties and informal relationships between the countries of the Allied Powers kept the majority of the coalition intact through both wars. Learn more about World War 2Sources: firstworldwar.com britannica.com Related Questions Q: What Was the Outcome of WWII? A: World War II ended on May 8, 1945, on the European front, when Germany surrendered to the Allied Powers. The war ended on the Japanese front on Sept. 2, 19... Full Answer >Filed Under: World War 2Q: How Did the Allies Win World War II? A: The Allies secured victory in World War II when Germany was overwhelmed by the strength of the Soviet Red Army, aid from the United States and the strategy... Full Answer >Filed Under: World War 2Q: Why Did the United States Become Part of WW2? A: Beginning in Europe in 1939, World War II was fought between the Axis (Germany, Japan and Italy) and the Allies (the United States, Great Britain and the S... Full Answer >Filed Under: World War 2Q: Who Were the Major Players in WWII? A: World War II was primarily a conflict between the Allies (the United States, the United Kingdom, France and Russia) and the Axis powers (Germany, Japan and... Full Answer >Filed Under: World War 2You May Also Like Q: What Is the Definition of a Highly Compensated Employee? Q: What Is the Definition of ""extinct Species""? Q: How Was Propaganda Used in WWII? Q: What Is the Definition of ""color"" in Art? Q: What Is the Definition of Living Things? Q: What Is Crevecoeur's Definition of an American? "
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[
"\"History Modern History World War 2Q: What Is the Definition of the Allied Powers?",
"A: Quick Answer The Allied Powers, or Allies, refers to coalitions of primarily North American nations victorious over rival, central-European forces in World War I and World War II.",
"The four nations that recurred as the main forces of the Allied Powers in both wars were France, Russia/USSR, the United Kingdom and the United States.",
"Continue Reading Keep Learning What Were the Axis Powers?",
"Which Countries Were the Allied Forces' Enemies During World War II?",
"What Are the Main Countries That Made up the Allied Powers?",
"Full Answer The antagonists of the Allied Powers in World Wars I and II were coalitions begun by Germany, the Central Powers and Axis Powers, respectively.",
"Italy, though an Allied Power during World War I, joined the Axis Powers under the leadership of Benito Mussolini, only to depose Mussolini in 1943 and fight the German occupation of their northern territories.",
"The inclusion of Japan into the Axis Powers made China join the Allied Powers.",
"Otherwise, the history of formal treaties and informal relationships between the countries of the Allied Powers kept the majority of the coalition intact through both wars.",
"Learn more about World War 2Sources: firstworldwar.com britannica.com Related Questions Q: What Was the Outcome of WWII?",
"A: World War II ended on May 8, 1945, on the European front, when Germany surrendered to the Allied Powers.",
"The war ended on the Japanese front on Sept. 2, 19... Full Answer >Filed Under: World War 2Q: How Did the Allies Win World War II?",
"A: The Allies secured victory in World War II when Germany was overwhelmed by the strength of the Soviet Red Army, aid from the United States and the strategy... Full Answer >Filed Under: World War 2Q: Why Did the United States Become Part of WW2?",
"A: Beginning in Europe in 1939, World War II was fought between the Axis (Germany, Japan and Italy) and the Allies (the United States, Great Britain and the S... Full Answer >Filed Under: World War 2Q: Who Were the Major Players in WWII?",
"A: World War II was primarily a conflict between the Allies (the United States, the United Kingdom, France and Russia) and the Axis powers (Germany, Japan and... Full Answer >Filed Under: World War 2You May Also Like Q: What Is the Definition of a Highly Compensated Employee?",
"Q: What Is the Definition of \"\"extinct Species\"\"?",
"Q: How Was Propaganda Used in WWII?",
"Q: What Is the Definition of \"\"color\"\" in Art?",
"Q: What Is the Definition of Living Things?",
"Q: What Is Crevecoeur's Definition of an American? \""
] |
D1659457
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http://www.ushistory.org/us/11.asp
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11. The American Revolution
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"11. The American Revolution When the possibility of a clash with the British became real, New England farmers began to arm themselves and train for battle. These troops were dubbed ""minutemen"" because they could be ready to fight in a minute. This monument to the minutemen stands in Concord, Massachusetts. How could the Americans ever hope defeat the mighty British Empire in a military conflict? Americans faced seemingly impossible obstacles. When the guns fired at Lexington and Concord in 1775, there was not yet even a Continental Army. Those battles were fought by local militias. Few Americans had any military experience, and there was no method of training, supplying, or paying an army. Moreover, a majority of Americans opposed the war in 1775. Many historians believe only about a third of all Americans supported a war against the British at that time. Further, the Colonies had a poor track record of working together. How, then, could a ragtag group of patriots defeat the British? Early Battles John Trumbull The Battle of Bunker Hill was not a military victory for the colonial forces, but it served as an important morale booster. The colonists inflicted heavy casualties on the larger, more powerful British forces. The early stages of war, in 1775, can be best described as British military victories and American moral triumphs. The British routed the minutemen at Lexington, but the relentless colonists unleashed brutal sniper fire on the British returning to Boston from Concord. In June 1775, the colonists failed to prevail at Bunker Hill, but inflicted heavy casualties on a vastly superior military force. A year later, in 1776, while the British occupied New York, Washington led his army to two surprise victories at Trenton and Princeton that uplifted the morale of the patriots. Regardless, by 1777 the British occupied Philadelphia, the seat of the Continental Congress, and sent that body into hiding. The British also controlled New York City and pretty much had their way in the waters along the Eastern Seaboard. In fact, there was no Continental Navy to speak of at this time. Meanwhile, the British began mounting a southward attack from Canada into upstate New York. This threatened to cut New England off from the rest of the Colonies. Saratoga and Valley Forge: The Tide Turns The Battle of Saratoga, in northern New York, served as a critical turning point. The British attempt to capture the Hudson River Valley ended with their surrender to General Horatio Gates in October. Washington, having lost Philadelphia, led his troops to Valley Forge to spend the winter. None of the world's powers had come to the aid of the patriot cause — yet. In early 1778, the French agreed to recognize American independence and formed a permanent alliance with the new nation. Military help and sizable stores of much-needed gunpowder soon arrived. The tide was beginning to turn. The surrender of Lord Cornwallis at Yorktown marked the end of the Revolutionary War. This painting by John Trumbull is 12 feet by 18 feet and hangs in the rotunda of the U. S. Capitol Building. A New Type of War The British grew increasingly frustrated. The loss at Saratoga was humiliating. Capturing the enemy's capital, Philadelphia, did not bring them much advantage. As long as the American Continental Army and state militias remained in the field, the British had to keep on fighting. And no matter how much damage the British did to American cities or private property, the Americans refused to surrender. This was a new type of war. Having failed in the north, the British turned their attention to the south. They hoped to inspire Loyalist support among dissatisfied Americans — a hope that was never realized. Fighting continued. The threat of French naval participation kept the British uneasy. A Stunning Defeat In October 1781, the war virtually came to an end when General Cornwallis was surrounded and forced to surrender the British position at Yorktown, Virginia. Two years later, the Treaty of Paris made it official: America was independent. How could the Americans ever hope defeat the mighty British Empire in a military conflict? Perhaps an even better question to ask is, How did the mighty British Empire ever expect to vanquish the Americans? Major Battles of the American Revolution Date Battle American Commander (s) British Commander April 19, 1775 Lexington-Concord Capt. John Parker Lt. Col. Francis Smith June 17, 1775 Bunker (Breed's) Hill Gen. Israel Putnam and Col. William Prescott Gen. William Howe Dec. 31, 1775 Quebec Gen. Richard Montgomery Gen. Guy Carleton Aug. 27, 1776 Long Island Gen. George Washington Gen. William Howe Oct. 26, 1776 White Plains Gen. George Washington Gen. William Howe Dec. 26, 1776 Trenton Gen. George Washington Col. Johann Rall Sept. 11, 1777 Brandywine Gen. George Washington Gen. William Howe Sept. 19, 1777 Saratoga (Freeman's Farm) Gen. Horatio Gates Gen. John Burgoyne Oct. 4, 1777 Germantown Gen. George Washington Gen. William Howe Oct. 7, 1777 Saratoga Gen. Horatio Gates Gen. John Burgoyne Dec. 5, 1777 White Marsh Gen. George Washington Gen. William Howe June 8, 1778 Monmouth Courthouse Gen. George Washington Gen. Henry Clinton Sept. 16, 1779 Siege of Savannah Gen. Benjamin Lincoln Gen. Augustine Prevost March 29, 1780 Siege of Charlestown Gen. Benjamin Lincoln Gen. Henry Clinton Sept. 28, 1781 Siege of Yorktown Gen. George Washington and Gen. Rochambeau Gen. Charles Cornwallis "
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[
"\"11.",
"The American Revolution When the possibility of a clash with the British became real, New England farmers began to arm themselves and train for battle.",
"These troops were dubbed \"\"minutemen\"\" because they could be ready to fight in a minute.",
"This monument to the minutemen stands in Concord, Massachusetts.",
"How could the Americans ever hope defeat the mighty British Empire in a military conflict?",
"Americans faced seemingly impossible obstacles.",
"When the guns fired at Lexington and Concord in 1775, there was not yet even a Continental Army.",
"Those battles were fought by local militias.",
"Few Americans had any military experience, and there was no method of training, supplying, or paying an army.",
"Moreover, a majority of Americans opposed the war in 1775.",
"Many historians believe only about a third of all Americans supported a war against the British at that time.",
"Further, the Colonies had a poor track record of working together.",
"How, then, could a ragtag group of patriots defeat the British?",
"Early Battles John Trumbull The Battle of Bunker Hill was not a military victory for the colonial forces, but it served as an important morale booster.",
"The colonists inflicted heavy casualties on the larger, more powerful British forces.",
"The early stages of war, in 1775, can be best described as British military victories and American moral triumphs.",
"The British routed the minutemen at Lexington, but the relentless colonists unleashed brutal sniper fire on the British returning to Boston from Concord.",
"In June 1775, the colonists failed to prevail at Bunker Hill, but inflicted heavy casualties on a vastly superior military force.",
"A year later, in 1776, while the British occupied New York, Washington led his army to two surprise victories at Trenton and Princeton that uplifted the morale of the patriots.",
"Regardless, by 1777 the British occupied Philadelphia, the seat of the Continental Congress, and sent that body into hiding.",
"The British also controlled New York City and pretty much had their way in the waters along the Eastern Seaboard.",
"In fact, there was no Continental Navy to speak of at this time.",
"Meanwhile, the British began mounting a southward attack from Canada into upstate New York.",
"This threatened to cut New England off from the rest of the Colonies.",
"Saratoga and Valley Forge: The Tide Turns The Battle of Saratoga, in northern New York, served as a critical turning point.",
"The British attempt to capture the Hudson River Valley ended with their surrender to General Horatio Gates in October.",
"Washington, having lost Philadelphia, led his troops to Valley Forge to spend the winter.",
"None of the world's powers had come to the aid of the patriot cause — yet.",
"In early 1778, the French agreed to recognize American independence and formed a permanent alliance with the new nation.",
"Military help and sizable stores of much-needed gunpowder soon arrived.",
"The tide was beginning to turn.",
"The surrender of Lord Cornwallis at Yorktown marked the end of the Revolutionary War.",
"This painting by John Trumbull is 12 feet by 18 feet and hangs in the rotunda of the U. S. Capitol Building.",
"A New Type of War The British grew increasingly frustrated.",
"The loss at Saratoga was humiliating.",
"Capturing the enemy's capital, Philadelphia, did not bring them much advantage.",
"As long as the American Continental Army and state militias remained in the field, the British had to keep on fighting.",
"And no matter how much damage the British did to American cities or private property, the Americans refused to surrender.",
"This was a new type of war.",
"Having failed in the north, the British turned their attention to the south.",
"They hoped to inspire Loyalist support among dissatisfied Americans — a hope that was never realized.",
"Fighting continued.",
"The threat of French naval participation kept the British uneasy.",
"A Stunning Defeat In October 1781, the war virtually came to an end when General Cornwallis was surrounded and forced to surrender the British position at Yorktown, Virginia.",
"Two years later, the Treaty of Paris made it official: America was independent.",
"How could the Americans ever hope defeat the mighty British Empire in a military conflict?",
"Perhaps an even better question to ask is, How did the mighty British Empire ever expect to vanquish the Americans?",
"Major Battles of the American Revolution Date Battle American Commander (s) British Commander April 19, 1775 Lexington-Concord Capt.",
"John Parker Lt. Col. Francis Smith June 17, 1775 Bunker (Breed's) Hill Gen. Israel Putnam and Col. William Prescott Gen. William Howe Dec. 31, 1775 Quebec Gen. Richard Montgomery Gen.",
"Guy Carleton Aug. 27, 1776 Long Island Gen. George Washington Gen. William Howe Oct. 26, 1776 White Plains Gen. George Washington Gen. William Howe Dec. 26, 1776 Trenton Gen. George Washington Col. Johann Rall Sept. 11, 1777 Brandywine Gen. George Washington Gen. William Howe Sept. 19, 1777 Saratoga (Freeman's Farm) Gen. Horatio Gates Gen. John Burgoyne Oct. 4, 1777 Germantown Gen. George Washington Gen. William Howe Oct. 7, 1777 Saratoga Gen. Horatio Gates Gen. John Burgoyne Dec. 5, 1777 White Marsh Gen. George Washington Gen. William Howe June 8, 1778 Monmouth Courthouse Gen. George Washington Gen. Henry Clinton Sept. 16, 1779 Siege of Savannah Gen. Benjamin Lincoln Gen. Augustine Prevost March 29, 1780 Siege of Charlestown Gen. Benjamin Lincoln Gen. Henry Clinton Sept. 28, 1781 Siege of Yorktown Gen. George Washington and Gen. Rochambeau Gen. Charles Cornwallis \""
] |
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