# migrations

dir: embeddings_queue
filename: 00001-embeddings.sqlite.sql
hash: d3755dfd232be8e8301f4d7fcfb3a486
sql:
CREATE TABLE embeddings_queue (
    seq_id INTEGER PRIMARY KEY,
    created_at TIMESTAMP NOT NULL DEFAULT CURRENT_TIMESTAMP,
    operation INTEGER NOT NULL,
    topic TEXT NOT NULL,
    id TEXT NOT NULL,
    vector BLOB,
    encoding TEXT,
    metadata TEXT
);


dir: sysdb
filename: 00001-collections.sqlite.sql
hash: 38352d725ad1c16074fac420b22b4633
sql:
CREATE TABLE collections (
    id TEXT PRIMARY KEY,
    name TEXT NOT NULL,
    topic TEXT NOT NULL,
    UNIQUE (name)
);

CREATE TABLE collection_metadata (
    collection_id TEXT REFERENCES collections(id) ON DELETE CASCADE,
    key TEXT NOT NULL,
    str_value TEXT,
    int_value INTEGER,
    float_value REAL,
    PRIMARY KEY (collection_id, key)
);


dir: sysdb
filename: 00002-segments.sqlite.sql
hash: 2913cb6a503055a95f625448037e8912
sql:
CREATE TABLE segments (
    id TEXT PRIMARY KEY,
    type TEXT NOT NULL,
    scope TEXT NOT NULL,
    topic TEXT,
    collection TEXT REFERENCES collection(id)
);

CREATE TABLE segment_metadata (
    segment_id TEXT  REFERENCES segments(id) ON DELETE CASCADE,
    key TEXT NOT NULL,
    str_value TEXT,
    int_value INTEGER,
    float_value REAL,
    PRIMARY KEY (segment_id, key)
);


dir: sysdb
filename: 00004-tenants-databases.sqlite.sql
hash: 048867ce8fcdefe4023c7110e4433591
sql:
CREATE TABLE IF NOT EXISTS tenants (
    id TEXT PRIMARY KEY,
    UNIQUE (id)
);

CREATE TABLE IF NOT EXISTS databases (
    id TEXT PRIMARY KEY, -- unique globally
    name TEXT NOT NULL, -- unique per tenant
    tenant_id TEXT NOT NULL REFERENCES tenants(id) ON DELETE CASCADE,
    UNIQUE (tenant_id, name) -- Ensure that a tenant has only one database with a given name
);

CREATE TABLE IF NOT EXISTS collections_tmp (
    id TEXT PRIMARY KEY, -- unique globally
    name TEXT NOT NULL, -- unique per database
    topic TEXT NOT NULL,
    dimension INTEGER,
    database_id TEXT NOT NULL REFERENCES databases(id) ON DELETE CASCADE,
    UNIQUE (name, database_id)
);

-- Create default tenant and database
INSERT OR REPLACE INTO tenants (id) VALUES ('default_tenant'); -- The default tenant id is 'default_tenant' others are UUIDs
INSERT OR REPLACE INTO databases (id, name, tenant_id) VALUES ('00000000-0000-0000-0000-000000000000', 'default_database', 'default_tenant');

INSERT OR REPLACE INTO collections_tmp (id, name, topic, dimension, database_id)
    SELECT id, name, topic, dimension, '00000000-0000-0000-0000-000000000000' FROM collections;
DROP TABLE collections;
ALTER TABLE collections_tmp RENAME TO collections;


dir: metadb
filename: 00001-embedding-metadata.sqlite.sql
hash: 2b4cf52c4bb2676e21d6860a4409f856
sql:
CREATE TABLE embeddings (
    id INTEGER PRIMARY KEY,
    segment_id TEXT NOT NULL,
    embedding_id TEXT NOT NULL,
    seq_id BLOB NOT NULL,
    created_at TIMESTAMP NOT NULL DEFAULT CURRENT_TIMESTAMP,
    UNIQUE (segment_id, embedding_id)
);

CREATE TABLE embedding_metadata (
    id INTEGER REFERENCES embeddings(id),
    key TEXT NOT NULL,
    string_value TEXT,
    int_value INTEGER,
    float_value REAL,
    PRIMARY KEY (id, key)
);

CREATE TABLE max_seq_id (
    segment_id TEXT PRIMARY KEY,
    seq_id BLOB NOT NULL
);

CREATE VIRTUAL TABLE embedding_fulltext USING fts5(id, string_value);


dir: metadb
filename: 00002-embedding-metadata.sqlite.sql
hash: 12a570f7121b3a8ce750a2a7c36da20f
sql:
-- SQLite does not support adding check with alter table, as a result, adding a check
-- involve creating a new table and copying the data over. It is over kill with adding
-- a boolean type column. The application write to the table needs to ensure the data
-- integrity.
ALTER TABLE embedding_metadata ADD COLUMN bool_value INTEGER


dir: metadb
filename: 00003-full-text-tokenize.sqlite.sql
hash: f97ad6334aeaa8f419f01110b648b97a
sql:
CREATE VIRTUAL TABLE embedding_fulltext_search USING fts5(string_value, tokenize='trigram');
INSERT INTO embedding_fulltext_search (rowid, string_value) SELECT rowid, string_value FROM embedding_metadata;
DROP TABLE embedding_fulltext;


# embeddings_queue

created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1
encoding: FLOAT32
metadata:
{"title": "2013 Alzheimer's disease facts and figures", "chroma:document": "Alzheimer\u2019s Association Report\n2013 Alzheimer\u2019s disease facts and \ufb01gures\nAlzheimer\u2019s Association*\nAbstract\nThis report provides information to increase understanding of the public health impact of Alz-\nheimer\u2019s disease (AD), including incidence and prevalence, mortality rates, health expenditures\nand costs of care, and effect on caregivers and society in general. It also explores the roles and unique\nchallenges of long-distance caregivers, as well as interventions that target those challenges. An\nestimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years\nwith AD comprise the younger onset AD population; 5 million comprise the older onset AD popu-\nlation. Throughout the coming decades, the baby boom generation is projected to add about 10\nmillion to the total number of people in the United States with AD. Today, someone in America\ndevelops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 sec-\nonds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8\nmillion. AD is the sixth leading cause of death in the United States and the \ufb01fth leading cause of death\nin Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from\nheart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the pro-\nportion resulting from AD increased 68%. The number of deaths from AD as determined by of\ufb01cial\ndeath certi\ufb01cates (83,494 in 2010) likely underrepresents the number of AD-related deaths in the\nUnited States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion\nwill die as a result of complications of AD. In 2012, more than 15 million family members and other\nunpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other\ndementias, a contribution valued at more than $216 billion. Medicare payments for services to ben-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 2
encoding: FLOAT32
metadata:
{"title": "2013 Alzheimer's disease facts and figures", "chroma:document": "e\ufb01ciaries age 65 years and older with AD and other dementias are three times as great as payments for\nbene\ufb01ciaries without these conditions, and Medicaid payments are 19 times as great. Total payments\nin 2013 for health care, long-term care, and hospice services for people age 65 years and older with\ndementia are expected to be $203 billion (not including the contributions of unpaid caregivers). An\nestimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from\nthe care recipient. These \u201clong-distance caregivers\u201d face unique challenges, including dif\ufb01culty in\nassessing the care recipient\u2019s true health condition and needs, high rates of family disagreement\nregarding caregiving decisions, and high out-of-pocket expenses for costs related to caregiving.\nOut-of-pocket costs for long-distance caregivers are almost twice as high as for local caregivers.\n\u0001 2013 The Alzheimer\u2019s Association.\nKeywords:\nAlzheimer\u2019s disease; Dementia; Diagnostic criteria; Prevalence; Incidence; Mortality; Caregivers; Family care-\ngiver; Spouse caregiver; Health care costs; Health care expenditures; Long-term care costs; Medicare spending;\nMedicaid spending; Long-distance caregiver; Activities of daily living; Instrumental activities of daily living\n1. About this report\n2013 Alzheimer\u2019s Disease Facts and Figures is a statisti-\ncal resource for US data related to Alzheimer\u2019s disease\n(AD), the most common type of dementia, as well as other\ndementias. Background and context for interpretation of\nthe data are contained in the Overview. This information\nincludes de\ufb01nitions of the various types of dementia and\na summary of current knowledge about AD. Additional\nsections address prevalence, mortality, caregiving, and\nuse and costs of care and services. This special report fo-\ncuses on long-distance caregivers of people with AD and\nother dementias.\nSpeci\ufb01c information in this year\u2019s Alzheimer\u2019s Disease\nFacts and Figures includes the following:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 3
encoding: FLOAT32
metadata:
{"title": "2013 Alzheimer's disease facts and figures", "chroma:document": "*Corresponding authors: William Thies, Ph.D., and Laura Bleiler. Tel.:\n312-335-5893; Fax: 866-521-8007. E-mail address: lbleiler@alz.org\n1552-5260\u0001 2013 The Alzheimer\u2019s Association.\nhttp://dx.doi.org/10.1016/j.jalz.2013.02.003\nAlzheimer\u2019s & Dementia 9 (2013) 208\u2013245\n. \nOpen access under CC BY-NC-ND license. \nOpen access under CC BY-NC-ND license."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 4
encoding: FLOAT32
metadata:
{"title": "Androgens increase excitatory neurogenic potential in human brain organoids", "chroma:document": "Androgens increase excitatory neurogenic potential in human \nbrain organoids\nIva Kelava1,3,*, Ilaria Chiaradia1, Laura Pellegrini1, Alex T. Kalinka2, Madeline A. \nLancaster1,*\n1Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue. CB2 0QH \nCambridge, United Kingdom\n2Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, \nCambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW\nAbstract\nThe biological basis of male-female brain differences has been difficult to elucidate in humans. \nThe most striking morphological difference is size, with males having on average a larger \nbrain than females 1,2 , yet a mechanistic understanding of how this difference arises remains \nto be elucidated. Here, we use brain organoids 3 to demonstrate that while sex chromosomal \ncomplement has no observable effect on neurogenesis, sex steroids, namely androgens, lead to \nincreased proliferation of cortical progenitors and an increased neurogenic pool. Transcriptomic \nanalysis and functional studies demonstrate downstream effects on HDAC activity and mTOR \npathway. Finally, we show that androgens specifically increase neurogenic output of excitatory \nneuronal progenitors, while inhibitory neuronal progenitors are not increased. These findings \nuncover a hitherto unknown role for androgens in regulating excitatory neuron number and \nrepresent a first step towards understanding the origin of human sex-related brain differences.\nIntroduction\nSex-based brain differences are controversial, yet negating their existence has detrimental \nconsequences for all sexes and genders, and for developing accurate diagnostic tools \nand effective drugs. One of the most striking differences is divergent susceptibility to \ncertain neurological conditions 4,5 , for example, autism spectrum disorder (ASD) 6 and \nschizophrenia 7 , pointing to differences in brain structure and/or function. Indeed, decades \nof research in model organisms has revealed numerous sex-specific morphological and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 5
encoding: FLOAT32
metadata:
{"title": "Androgens increase excitatory neurogenic potential in human brain organoids", "chroma:document": "behavioural differences 8\u201310 . However, the presence of sex-specific characteristics in \n* Corresponding authors: Correspondence to Iva Kelava or Madeline A. Lancaster. mlancast@mrc-lmb.cam.ac.uk, \nik9@sanger.ac.uk .\n3Current address: Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1RQ\nAuthor contributions \nI.K. conceived the study, performed experiments, analysed data and wrote the paper. I.C. performed experiments and analysed the \ndata. L.P. performed experiments. A.T.K. performed bioinformatics analysis. M.A.L. supervised the study, analysed data and co-wrote \nthe paper.\nConflict of interest \nM.A.L. is an inventor on several patents related to cerebral organoids, is co-founder and scientific advisory board member of a:head \nbio, and scientific advisory board member of the Roche Institute for Translational Bioengineering.\nEurope PMC Funders Group\nAuthor Manuscript\nNature. Author manuscript; available in PMC 2022 August 01.\nPublished in final edited form as:\nNature. 2022 February 01; 602(7895): 112\u2013116. doi:10.1038/s41586-021-04330-4.\n Europe PMC Funders Author Manuscripts\n Europe PMC Funders Author Manuscripts"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 6
encoding: FLOAT32
metadata:
{"title": "Association Between Levels of Hormones and Risk of Esophageal Adenocarcinoma and Barrett\\220s Esophagus", "chroma:document": "Association Between Levels of Hormones and Risk of \nEsophageal Adenocarcinoma and Barrett\u2019s Esophagus\nShao-Hua Xie*,a, Rui Fang\u2021,a, Mingtao Huang\u2021, Juncheng Dai\u2021,\u00a7, Aaron P. Thrift\u2225,\u00b6, Lesley A. \nAnderson#, Wong-Ho Chow**, Leslie Bernstein\u2021\u2021, Marilie D. Gammon\u00a7\u00a7, Harvey A. Risch\u2225\u2225, \nNicholas J. Shaheen\u00b6\u00b6, Brian J. Reid##, Anna H. Wu***, Prasad G. Iyer\u2021\u2021\u2021, Geoffrey Liu\u00a7\u00a7\u00a7, \nDouglas A. Corley\u2225\u2225\u2225, David C. Whiteman\u00b6\u00b6\u00b6, Carlos Caldas###, Paul D. Pharoah****,\u2021\u2021\u2021\u2021, \nLaura J. Hardie\u00a7\u00a7\u00a7\u00a7, Rebecca C. Fitzgerald\u2225\u2225\u2225\u2225, Hongbing Shen\u2021,\u00a7, Thomas L. Vaughan##, \nJesper Lagergren*,\u00b6\u00b6\u00b6\u00b6\n*Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska \nInstitutet, Karolinska University Hospital, Stockholm, Sweden\n\u2021Department of Epidemiology and Biostatistics, International Joint Research Center on \nEnvironment and Human Health, Center for Global Health, School of Public Health\n\u00a7Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Collaborative Innovation \nCenter for Cancer Medicine, Nanjing Medical University, Nanjing, China\n\u2225Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas\n\u00b6Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of \nMedicine, Houston, Texas\n#Centre for Public Health, Queen\u2019s University Belfast, Belfast, United Kingdom\n**Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas\n\u2021\u2021Department of Population Sciences, Beckman Research Institute, City of Hope Comprehensive \nCancer Center, Duarte, California\n\u00a7\u00a7Department of Epidemiology, Gillings School of Global Public Health\n\u00b6\u00b6Division of Gastroenterology and Hepatology, School of Medicine, University of North Carolina, \nChapel Hill, North Carolina\n\u2225\u2225Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, \nConnecticut\n##Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, \nWashington"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 7
encoding: FLOAT32
metadata:
{"title": "Association Between Levels of Hormones and Risk of Esophageal Adenocarcinoma and Barrett\\220s Esophagus", "chroma:document": "Reprint requests: Address requests for reprints to: Shao-Hua Xie, MD, PhD, Upper Gastrointestinal Surgery, Department of \nMolecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, NS 67, SE 171 76 Stockholm, Sweden. \nshaohua.xie@ki.se.\naAuthors share co-first authorship.\nConflicts of interest\nThe authors disclose no conflicts.\nSupplementary Material\nNote: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and \nHepatology at www.cghjournal.org, and at https://doi.org/10.1016/jxgh.2019.11.030.\nHHS Public Access\nAuthor manuscript\nClin Gastroenterol Hepatol. Author manuscript; available in PMC 2020 November 01.\nPublished in final edited form as:\nClin Gastroenterol Hepatol. 2020 November ; 18(12): 2701\u20132709.e3. doi:10.1016/j.cgh.2019.11.030.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 8
encoding: FLOAT32
metadata:
{"title": "\u008dDepressed\u008e caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson's disease", "chroma:document": "Contents lists available at ScienceDirect\nNeurobiology of Disease\njournal homepage: www.elsevier.com/locate/ynbdi\n\u201cDepressed\u201d caudate and ventral striatum dopamine transporter availability\nin de novo Depressed Parkinson's disease\nSang-Won Yooa, Yoon-Sang Oha, Eo-Jin Hwanga,b, Dong-Woo Ryua, Kwang-Soo Leea,\nChul Hyoung Lyooc, Joong-Seok Kima,\u204e\na Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea\nb Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea\nc Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea\nA R T I C L E I N F O\nKeywords:\nParkinson's disease\nDepression\nDopamine transporter uptake\nMontgomery\u2013Asberg depression rating scale\nCaudate\nVentral striatum\nA B S T R A C T\nDepression can occur before the onset of motor symptoms in Parkinson's disease (PD) patients. The pathophy-\nsiology of depression in PD involves various brain regions and relevant functional circuits. This study in-\nvestigated whether there exist distinctive patterns of presynaptic monoamine transporter densities in the basal\nganglia depending on the degree of depression in patients with PD. A total of 123 early and drug-na\u00efve PD\npatients were enrolled. Their a\ufb00ective status was evaluated by the Montgomery\u2013Asberg Depression Rating Scale\n(MADRS), and subjects were subgrouped into one of the following three groups according to their MADRS\nscores: no depression, mild depression, and moderate-to-severe depression. All patients underwent positron\nemission tomography (PET)\nusing\n18F-N-(3-\ufb02uoropropyl)-2beta-carbon\nethoxy-3beta-(4-iodophenyl)\nnor-\ntropane. The PET images were normalized, and di\ufb00erences in the regional standardized uptake value ratios\n(SUVRs) for each side of the caudate, putamen, globus pallidus, thalamus, and ventral striatum were analyzed\nand compared between the three groups. A trend analysis was performed across the groups to discern any"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 9
encoding: FLOAT32
metadata:
{"title": "\u008dDepressed\u008e caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson's disease", "chroma:document": "associations between SUVR values of the basal ganglia and depression severity. The SUVR values of the caudate,\nanterior caudate nuclei, and ventral striatum declined as MADRS increased. The SUVR values of the striatum\nshowed an inverse dose-dependent trend of antero- and ventroposterior gradient across the groups. This result\nindirectly revealed the involvement of the associative and limbic circuitry of the brain that are modulated by\nmonoamines in early PD with depression. This might suggest an in vivo causal relationship between the ventral\nstriatum, caudate and depression.\n1. Introduction\nMood disturbances, such as depression, are known to occur even\nbefore the onset of motor symptoms in patients with Parkinson's disease\n(PD) (Pont-Sunyer et al., 2015). The prevalence of depression in PD is\nestimated to be 30\u201335%; the mild depressive mood often persists during\ndisease progression and is a risk factor for moderate to severe depres-\nsion (Aarsland et al., 2011).\nDepression involves di\ufb00erent sets of regional brain circuitry, such as\nthe limbic and associative loops, and information processing through\nthese circuits is mediated by distinctive monoamines, such as dopa-\nmine, serotonin, and noradrenaline, relevant to the particular brain\nareas (Aarsland et al., 2011; Stahl, 2013; Tremblay et al., 2015). When\nthese connections are disrupted, depression occurs. It has been known\nthat PD pathology encroaches upon these circuits, evoking mood dis-\norders (Aarsland et al., 2011; Frisina et al., 2009).\n18F-N-(3-\ufb02uoropropyl)-2beta-carbon\nethoxy-3beta-(4-iodophenyl)\nnortropane (18F-FP-CIT) and positron emission tomography (PET) can\nassess the functional integrity of the presynaptic nigrostriatal system. It\nhas now become an important, albeit not essential, tool in diagnosing\nidiopathic PD (K\u00e4gi et al., 2010; Postuma et al., 2015). Not only does it\nre\ufb02ect PD severity, it also implicates the interactions of di\ufb00erent\nmonoaminergic systems, such as the dopaminergic, noradrenergic, and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 10
encoding: FLOAT32
metadata:
{"title": "\u008dDepressed\u008e caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson's disease", "chroma:document": "serotonergic systems (Hesse et al., 2009; Remy et al., 2005).\nIn PD, the posterior and dorsal striatum (sensorimotor territory) is\nmore a\ufb00ected than the anterior and ventral parts of the striatum (as-\nsociative and limbic territories) (Tremblay et al., 2015). Depending on\nthe distinctive brain circuits, a di\ufb00erent threshold of dopaminergic\nhttps://doi.org/10.1016/j.nbd.2019.104563\nReceived 19 June 2019; Received in revised form 26 July 2019; Accepted 31 July 2019\n\u204e Corresponding author at: Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, 222, Banpo-daero, Seocho-\ngu, Seoul 06591, Republic of Korea.\nE-mail address: neuronet@catholic.ac.kr (J.-S. Kim).\nNeurobiology of Disease 132 (2019) 104563\nAvailable online 01 August 2019\n0969-9961/ \u00a9\n 2019 Elsevier Inc. All rights reserved.\nT"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 11
encoding: FLOAT32
metadata:
{"title": "Experimental and Statistical Considerations to Avoid False Conclusions in Proteomics Studies Using Differential In-gel Electrophoresis*", "chroma:document": "Experimental and Statistical Considerations to\nAvoid False Conclusions in Proteomics Studies\nUsing Differential In-gel Electrophoresis*\u25a1\nS\nNatasha A. Karp\u2021\u00a7, Paul S. McCormick\u00b6\u0001, Matthew R. Russell\u2021**,\nand Kathryn S. Lilley\u2021 \u2021\u2021\nIn quantitative proteomics, the false discovery rate (FDR)\ncan be defined as the number of false positives within\nstatistically significant changes in expression. False posi-\ntives accumulate during the simultaneous testing of expres-\nsion changes across hundreds or thousands of protein or\npeptide species when univariate tests such as the Student\u2019s\nt test are used. Currently most researchers rely solely on\nthe estimation of p values and a significance threshold, but\nthis approach may result in false positives because it does\nnot account for the multiple testing effect. For each spe-\ncies, a measure of significance in terms of the FDR can be\ncalculated, producing individual q values. The q value main-\ntains power by allowing the investigator to achieve an ac-\nceptable level of true or false positives within the calls of\nsignificance. The q value approach relies on the use of the\ncorrect statistical test for the experimental design. In this\nsituation, a uniform p value frequency distribution when\nthere are no differences in expression between two sam-\nples should be obtained. Here we report a bias in p value\ndistribution in the case of a three-dye DIGE experiment\nwhere no changes in expression are occurring. The bias\nwas shown to arise from correlation in the data from the use\nof a common internal standard. With a two-dye schema,\nwhere each sample has its own internal standard, such bias\nwas removed, enabling the application of the q value to two\ndifferent proteomics studies. In the case of the first study,\nwe demonstrate that 80% of calls of significance by the\nmore traditional method are false positives. In the second,\nwe show that calculating the q value gives the user control\nover the FDR. These studies demonstrate the power and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 12
encoding: FLOAT32
metadata:
{"title": "Experimental and Statistical Considerations to Avoid False Conclusions in Proteomics Studies Using Differential In-gel Electrophoresis*", "chroma:document": "ease of use of the q value in correcting for multiple testing.\nThis work also highlights the need for robust experimental\ndesign that includes the appropriate application of statisti-\ncal\nprocedures.\nMolecular\n&\nCellular\nProteomics\n6:\n1354\u20131364, 2007.\nQuantitative proteomics, the study of global changes in\nprotein expression, is a rapidly growing field where two-di-\nmensional (2D)1 gel electrophoresis (1, 2), differential labeling\nof protein and peptides with stable isotopes (3), and label-free\nmass spectrometric peak intensity measurements (4) are piv-\notal approaches to measuring changes in the expression level\nof proteins. The output of large scale genomic sequencing\nand gene expression studies have driven the need to globally\nassess protein behavior, which is central to our understanding\nof cellular function and disease processes. In quantitative\nstudies, the quantitation of the protein or peptide signal allows\nthe comparison of protein levels from one state with another.\nRegardless of the technique used, the data generated can be\nanalyzed with a variety of statistical approaches. In a simple\ncomparison of two samples, changes in protein expression\nare considered to be significant when above a specified\nthreshold (5). More rigorous studies incorporating replicates\nuse univariate (1, 6) or multivariate statistical methods (1, 7) to\nanalyze the data. Univariate methods, such as the Student\u2019s t\ntest, analyze the data from each individual protein species to\ndetermine whether the differences between the samples are\nsignificant. In multivariate methods, such as principle compo-\nnent analysis, all the data are simultaneously analyzed to look\nfor patterns in expression. Each of these statistical methods\ninvolves a number of mathematical assumptions; however,\nthese assumptions are often ignored, potentially leading to\nerroneous results (8). Regardless of the analytical method\nused to collect the proteomics data, subtle issues with sta-\ntistical analysis must be overcome to ensure that valid con-\nclusions are made."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 13
encoding: FLOAT32
metadata:
{"title": "Experimental and Statistical Considerations to Avoid False Conclusions in Proteomics Studies Using Differential In-gel Electrophoresis*", "chroma:document": "To date, the majority of published quantitative proteomics\nstudies have used the established 2D gel electrophoresis\napproach for quantitation and applied a univariate test to\nidentify protein species with significant changes in expression\n(8), although an increased number of studies are now using\nnon-gel-based approaches. These tests calculate the proba-\nbility (p) of observing a test statistic more extreme than the\none calculated from the data given that the samples are from\nthe same population (i.e. that any apparent change in expres-\nsion occurs by chance alone). Typically an expression change\nFrom the \u2021Department of Biochemistry, University of Cambridge,\nBuilding O, Downing Site, Cambridge CB2 1QW, United Kingdom and\n\u00b6Department of Chemistry, University Chemical Laboratory, Lensfield\nRoad, Cambridge CB2 1EW, United Kingdom\nReceived, July 26, 2006, and in revised form, May 14, 2007\nPublished, MCP Papers in Press, May 17, 2007, DOI 10.1074/\nmcp.M600274-MCP200\n1 The abbreviations used are: 2D, two-dimensional; FDR, false\ndiscovery rate; SA, standardized abundance; ECA, E. carotovora;\nPCER, per comparison error rate; FWER, familywise error rate; Q,\nquantile.\nResearch\n\u00a9 2007 by The American Society for Biochemistry and Molecular Biology, Inc.\n1354\nMolecular & Cellular Proteomics 6.8\nThis paper is available on line at http://www.mcponline.org\nThis is an Open Access article under the CC BY license."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 14
encoding: FLOAT32
metadata:
{"title": "A comprehensive transcriptional map of primate brain development", "chroma:document": "0 0  M O N T H  2 0 1 6  |  V O L  0 0 0  |  N A T U R E  |  1\nARTICLE\ndoi:10.1038/nature18637\nA comprehensive transcriptional map of \nprimate brain development\nTrygve E. Bakken1*, Jeremy A. Miller1*, Song-Lin Ding1*, Susan M. Sunkin1, Kimberly A. Smith1, Lydia Ng1, Aaron Szafer1, \nRachel A. Dalley1, Joshua J. Royall1, Tracy Lemon1, Sheila Shapouri1, Kaylynn Aiona1, James Arnold1, Jeffrey L. Bennett2, \nDarren Bertagnolli1, Kristopher Bickley1, Andrew Boe1, Krissy Brouner1, Stephanie Butler1, Emi Byrnes1, Shiella Caldejon1, \nAnita Carey1, Shelby Cate1, Mike Chapin1, Jefferey Chen1, Nick Dee1, Tsega Desta1, Tim A. Dolbeare1, Nadia Dotson1, \nAmanda Ebbert1, Erich Fulfs1, Garrett Gee1, Terri L. Gilbert1, Jeff Goldy1, Lindsey Gourley1, Ben Gregor1, Guangyu Gu1, Jon Hall1, \nZeb Haradon1, David R. Haynor3, Nika Hejazinia1, Anna Hoerder-Suabedissen4, Robert Howard1, Jay Jochim1, Marty Kinnunen1, \nAli Kriedberg1, Chihchau L. Kuan1, Christopher Lau1, Chang-Kyu Lee1, Felix Lee1, Lon Luong1, Naveed Mastan1, Ryan May1, \nJose Melchor1, Nerick Mosqueda1, Erika Mott1, Kiet Ngo1, Julie Nyhus1, Aaron Oldre1, Eric Olson1, Jody Parente1, \nPatrick D. Parker1, Sheana Parry1, Julie Pendergraft1, Lydia Potekhina1, Melissa Reding1, Zackery L. Riley1, Tyson Roberts1, \nBrandon Rogers1, Kate Roll1, David Rosen1, David Sandman1, Melaine Sarreal1, Nadiya Shapovalova1, Shu Shi1, Nathan Sjoquist1, \nAndy J. Sodt1, Robbie Townsend1, Lissette Velasquez1, Udi Wagley1, Wayne B. Wakeman1, Cassandra White1, Crissa Bennett1, \nJennifer Wu1, Rob Young1, Brian L. Youngstrom1, Paul Wohnoutka1, Richard A. Gibbs5, Jeffrey Rogers5, John G. Hohmann1, \nMichael J. Hawrylycz1, Robert F. Hevner6, Zolt\u00e1n Moln\u00e1r4, John W. Phillips1, Chinh Dang1, Allan R. Jones1, David G. Amaral2, \nAmy Bernard1 & Ed S. Lein1\nThe primate brain develops through a series of stereotyped processes \nthat are conserved across mammals1, including the specification, \nmigration, and maturation of diverse cell types and the formation and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 15
encoding: FLOAT32
metadata:
{"title": "A comprehensive transcriptional map of primate brain development", "chroma:document": "refinement of functional neuronal circuits. There are also primate- \nspecific features of brain development that increase anatomical2, \ncognitive3, and behavioural complexity4, and may explain why many \nhuman neurological and neuropsychiatric diseases are inadequately \nmodelled in rodents5. These features include a larger cortical progen-\nitor pool in the outer subventricular zone not present in rodents2 and \nprotracted myelination6, synapse production7, and pruning8. Rhesus \nmonkeys and humans share a greatly expanded neocortex and special-\nization of areas (most notably primary visual cortex2), compared to \nmouse brains, reflecting the more recent common ancestor of humans \nand rhesus monkeys (25\u00a0million years ago) than humans and mice \n(70\u00a0million years ago)9. Likewise, the rhesus monkey and human \nbrain10 share more similar patterns of gene expression than do mouse \nand human brains11. The rhesus monkey thus provides a valuable proxy \nfor human brain development, particularly during prenatal and early \npostnatal development stages that are difficult to sample in humans, \nand also provides a comparator to study human-specific features such \nas prolonged maturation or neoteny6,12,13.\nMolecular programs responsible for brain development remain \nincompletely understood in any species, due to the spatiotemporal \ncomplexity of these processes and the resource intensity of methods \nneeded to probe them. Transcriptome-based approaches have accel-\nerated understanding of variation in gene expression programs related \nto brain structure and function in adult and developing humans14\u201317 \nand rhesus monkeys10,18, albeit with limited anatomical resolution and \ndevelopmental coverage. Recent studies in adult mice19,20 and humans21 \nhave profiled individual cortical cells and demonstrated robust tran-\nscriptional differences between neuronal and non-neuronal cell types \nand large-scale changes over the course of development. Although \nthese approaches offer cellular resolution in targeted domains, a global"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 16
encoding: FLOAT32
metadata:
{"title": "A comprehensive transcriptional map of primate brain development", "chroma:document": "picture of gene expression changes over development across the com-\nplete cellular milieu has been lacking.\nThis project had the aim of creating a transcriptional atlas of non- \nhuman primate brain, combining fine anatomical precision with \ndense temporal coverage across prenatal and postnatal development \nThe transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely \nrelated non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) \nbrain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical \ndivision of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes \nmore rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like \nmolecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental \ntiming of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including \ncell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, \nautism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment \nwithin developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, \nalthough approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny \ncompared to monkey.\n1Allen Institute for Brain Science, Seattle, Washington 98109, USA. 2Department of Psychiatry and Behavioral Science, California National Primate Research Center, The M.I.N.D. Institute, \nUniversity of California, Davis, Sacramento, California 95817, USA. 3Department of Radiology, University of Washington, Seattle, Washington 98195, USA. 4Department of Physiology, Anatomy"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 17
encoding: FLOAT32
metadata:
{"title": "A comprehensive transcriptional map of primate brain development", "chroma:document": "and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. 5Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, \nHouston, Texas 77030, USA. 6Center for Integrative Brain Research, Seattle Children\u2019s Research Institute, Seattle, Washington 98101, USA.\n*These authors contributed equally to this work.\n\u00a9 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 18
encoding: FLOAT32
metadata:
{"title": "A current view on Tau protein phosphorylation in Alzheimer's disease", "chroma:document": "A current view on Tau protein phosphorylation in\nAlzheimer\u2019s disease\nSusanne Wegmann1, Jacek Biernat2 and\nEckhard Mandelkow2\nAbstract\nThe functions of the neuronal microtubule-associated protein\nTau in the central nervous system are regulated by manifold\nposttranslational modifications at more than 50 sites. Tau in\nhealthy neurons carries multiple phosphate groups, mostly in\nits microtubule assembly domain. Elevated phosphorylation\nand aggregation of Tau are widely considered pathological\nhallmarks in Alzheimer\u2019s disease (AD) and other tauopathies,\ntriggering the quest for Tau posttranslational modifications in\nthe disease context. However, the phosphorylation patterns of\nphysiological and pathological Tau are surprisingly similar and\nheterogenous, making it difficult to identify specific modifica-\ntions as therapeutic targets and biomarkers for AD. We present\na concise summary of - and view on - important previous and\nrecent advances in Tau phosphorylation analysis in the context\nof AD.\nAddresses\n1 German Center for Neurodegenerative Diseases (DZNE), Berlin,\nGermany\n2 German Center for Neurodegenerative Diseases (DZNE) & CAESAR\nResearch Center, Bonn, Germany\nCorresponding author: Wegmann, Susanne (susanne.wegmann@\ndzne.de)\nCurrent Opinion in Neurobiology 2021, 69:131\u2013138\nThis review comes from a themed issue on Molecular Neuroscience\nEdited by Frank Bradke and Yukiko Goda\nFor a complete overview see the Issue and the Editorial\nhttps://doi.org/10.1016/j.conb.2021.03.003\n0959-4388/\u00a9 2021 The Authors. Published by Elsevier Ltd. This is an\nopen access article under the CC BY-NC-ND license (http://\ncreativecommons.org/licenses/by-nc-nd/4.0/).\nAbbreviations\nSer, serine; Thr, threonine; Tyr, tyrosine; Lys, lysine; Arg, arginine; Leu,\nLeucine; G, Gly; TBS, tris-buffered saline; GG, glycine\u2013glycine; LRGG,\nLeu\u2013Arg\u2013Gly\u2013Gly; AD, Alzheimer\u2019s disease; CSF, cerebrospinal fluid;\nMAP, microtubule-associated protein; MAPT, Tau gene; MT, microtu-\nbule; MS, mass spectrometry; NFTs, neurofibrillary tangles; PTM, post-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 19
encoding: FLOAT32
metadata:
{"title": "A current view on Tau protein phosphorylation in Alzheimer's disease", "chroma:document": "translational modification; Pi, phosphate group; PRR, proline-rich region\n(of Tau protein); RD, repeat domain (of Tau protein); Rg, radius of\ngyration.\nIntroduction\nThe microtubule-associated protein Tau contributes to\nthe stability of axonal microtubules (MTs) in the brain\nand, in this role, is involved in the regulation of axon\noutgrowth and axonal transport. The binding of Tau to\nMTs is regulated by post-translational modi\ufb01cations\n(PTMs), mostly phosphorylation [14], which also con-\ntrols various other less characterized functions of Tau\n[51]. Tau was initially discovered by Kirschner and col-\nleagues, in a search for MT-associated proteins (MAPs)\nthat enhance MTself-assembly [61]. From a biomedical\nperspective, the interest in Tau rose sharply when Tau\nwas identi\ufb01ed as a principal component of neuro\ufb01bril-\nlary tangles (NFTs), a pathological hallmark found in the\nbrains of Alzheimer\u2019s disease (AD) [27]. By implication,\nthe progressive pathological accumulation of phosphor-\nylated and aggregated Tau has since been used for the\nstaging of AD and other tauopathies [10,33]. However,\nthe causal relationship between phosphorylation and\naggregation is still a matter of debate. Interestingly, fetal\nTau and Tau from AD brain appear to have a similar high\nTau phosphorylation levels, despite the absence of ag-\ngregation of fetal Tau during neuronal development\n[12,38,63].\nTau\nis\na\nhighly\nsoluble\nintrinsically\ndisordered\nprotein that occurs in six main isoforms in the human\ncentral nervous system [25]. The isoforms differ in their\ncontent of three alternatively spliced exons, producing\nTau isoforms with 0, 1, or 2 inserts in the N-terminal\nprojection domain (N1 and N2 isoforms), and 3 or 4\npseudo-repeats (3R and 4R isoforms) in the Tau repeat\ndomain (RD), which covers most of the MT-assembly\ndomain1\nand\nis\nresponsible\nfor\nTau\naggregation\n(Figure 1). Along the amino acid (aa) sequence of Tau,\nw85 putative phosphorylation sites (p-sites) have been\npredicted (Ser, Thr, Tyr), of which >50 are found to be"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 20
encoding: FLOAT32
metadata:
{"title": "A current view on Tau protein phosphorylation in Alzheimer's disease", "chroma:document": "modi\ufb01ed in Tau ([21,42]; Tau phosphorylation site\ntable: https://www.kcl.ac.uk/people/diane-hanger). The\ndistribution of p-sites in the Tau sequence is asym-\nmetric, such that most of the nonmodi\ufb01ed sites are\nlocated in the acidic N-terminal half (up to residue\n1 The RD (Figure 1) is often described in the literature as \u2018microtubule-binding\ndomain\u2019 (MTBD). This term is misleading, as the RD alone has only a weak af\ufb01nity for\nmicrotubules. Ef\ufb01cient binding and assembly of microtubules is achieved by the RD\nplus the \ufb02anking domains, herein denoted as \u2018MT assembly domain\u2019 (Figure 1).\nAvailable online at www.sciencedirect.com\nScienceDirect\nCurrent Opinion in\nNeurobiology\nwww.sciencedirect.com\nCurrent Opinion in Neurobiology 2021, 69:131\u2013138"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 21
encoding: FLOAT32
metadata:
{"title": "A deep proteome and transcriptome abundance atlas of 29 healthy human tissues", "chroma:document": "Article\nA deep proteome and transcriptome abundance\natlas of 29 healthy human tissues\nDongxue Wang1,\u2020\n, Basak Eraslan2,3,\u2020, Thomas Wieland4, Bj\u00f6rn Hallstr\u00f6m5, Thomas Hopf4,\nDaniel Paul Zolg1, Jana Zecha1, Anna Asplund6, Li-hua Li1, Chen Meng1, Martin Frejno1\n,\nTobias Schmidt1, Karsten Schnatbaum7, Mathias Wilhelm1, Frederik Ponten6\n, Mathias Uhlen5,\nJulien Gagneur2,*\n, Hannes Hahne4,**\n& Bernhard Kuster1,8,***\nAbstract\nGenome-,\ntranscriptome-\nand\nproteome-wide\nmeasurements\nprovide\ninsights\ninto\nhow\nbiological\nsystems\nare\nregulated.\nHowever, fundamental aspects relating to which human proteins\nexist, where they are expressed and in which quantities are not\nfully understood. Therefore, we generated a quantitative proteome\nand transcriptome abundance atlas of 29 paired healthy human\ntissues from the Human Protein Atlas project representing human\ngenes by 18,072 transcripts and 13,640 proteins including 37 with-\nout\nprior\nprotein-level\nevidence.\nThe\nanalysis\nrevealed\nthat\nhundreds of proteins, particularly in testis, could not be detected\neven for highly expressed mRNAs, that few proteins show tissue-\nspecific expression, that strong differences between mRNA and\nprotein quantities within and across tissues exist and that protein\nexpression is often more stable across tissues than that of tran-\nscripts. Only 238 of 9,848 amino acid variants found by exome\nsequencing could be confidently detected at the protein level\nshowing that proteogenomics remains challenging, needs better\ncomputational methods and requires rigorous validation. Many\nuses of this resource can be envisaged including the study of gene/\nprotein expression regulation and biomarker specificity evaluation.\nKeywords human proteome; human transcriptome; proteogenomics;\nquantitative mass spectrometry; RNA-Seq\nSubject Categories Genome-Scale & Integrative Biology; Methods &\nResources\nDOI 10.15252/msb.20188503 | Received 20 June 2018 | Revised 1 January\n2019 | Accepted 8 January 2019\nMol Syst Biol. (2019) 15: e8503\nSee also: B Eraslan et al (February 2019)"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 22
encoding: FLOAT32
metadata:
{"title": "A deep proteome and transcriptome abundance atlas of 29 healthy human tissues", "chroma:document": "Introduction\nDelineating the factors that govern protein expression and activity\nin cells is among the most fundamental research topics in biology.\nAlthough the number of potential protein-coding genes in the\nhuman genome is stabilizing at about 20,000, high-quality evidence\nfor their physical existence has not yet been found for all and\nintense efforts are ongoing to identify these currently ~13% \u201cmiss-\ning proteins\u201d (Omenn et al, 2017). While it is also generally\naccepted that the quantities of proteins vary greatly within and\nacross different cell types, tissues and body fluids (Kim et al, 2014;\nWilhelm et al, 2014), this has not been analysed systematically for\nmany human tissues. Furthermore, it is not very clear yet how the\nmany anabolic and catabolic processes are coordinated to give rise\nto the often vast differences in the levels of proteins. Messenger\nRNA levels are important determinants for protein abundance\n(Vogel et al, 2010; Schwanha\u00a8usser et al, 2011), and extensive\nmRNA expression maps of human cell types and tissues have been\ngenerated as proxies for estimating protein abundance (GTEx\nConsortium, 2013; Uhle\u00b4n et al, 2015; Thul et al, 2017). However,\nother studies have also highlighted the much higher dynamic range\nof protein than transcript abundance as well as a rather poor\ncorrelation of mRNA and protein levels suggesting that further and\npossibly\ndiverse\nregulatory\nelements\nplay\nimportant\nroles\n(Schwanha\u00a8usser et al, 2011; Liu et al, 2016; Franks et al, 2017).\nDecades of careful research revealed numerous mRNA elements\naffecting translation or mRNA stability such as codon usage, start\n1\nChair of Proteomics and Bioanalytics, Technische Universit\u00e4t M\u00fcnchen, Freising, Germany\n2\nComputational Biology, Department of Informatics, Technical University of Munich, Garching bei M\u00fcnchen, Germany\n3\nDepartment of Biochemistry, Quantitative Biosciences Munich, Gene Center, Ludwig Maximilian Universit\u00e4t, M\u00fcnchen, Germany\n4 OmicScouts GmbH, Freising, Germany\n5"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 23
encoding: FLOAT32
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{"title": "A deep proteome and transcriptome abundance atlas of 29 healthy human tissues", "chroma:document": "5\nScience for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden\n6\nScience for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden\n7\nJPT Peptide Technologies GmbH, Berlin, Germany\n8\nCenter for Integrated Protein Science Munich (CIPSM), Munich, Germany\n*Corresponding author. Tel: +49 89 289 19411; E-mail: gagneur@in.tum.de\n**Corresponding author. Tel: +49 8161 976289 0; Fax: +49 8161 976289 1; E-mail: hannes.hahne@omicscouts.com\n***Corresponding author. Tel: +49 8161 71 5696; Fax: +49 8161 71 5931; E-mail: kuster@tum.de\n\u2020These authors contributed equally to this work\n\u00aa 2019 The Authors. Published under the terms of the CC BY 4.0 license\nMolecular Systems Biology\n15: e8503 | 2019\n1 of 16"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 24
encoding: FLOAT32
metadata:
{"title": "A Draft Map of Rhesus Monkey Tissue Proteome for Biomedical Research", "chroma:document": "RESEARCH ARTICLE\nA Draft Map of Rhesus Monkey Tissue\nProteome for Biomedical Research\nJin-Gyun Lee1, Kimberly Q. McKinney1, Yong-Yook Lee1, Hae-Na Chung1, Antonis\nJ. Pavlopoulos1, Kook Y. Jung1, Woong-Ki Kim2, Marcelo J. Kuroda3, David K. Han4,\nSunil Hwang1*\n1 Proteomics Laboratory for Clinical and Translational Research, Carolinas HealthCare System, Charlotte,\nNorth Carolina, United States of America, 2 Department of Microbiology and Molecular Cell Biology, Eastern\nVirginia Medical School, Norfolk, Virginia, United States of America, 3 Tulane National Primate Research\nCenter, Tulane University, Covington, Louisiana, United States of America, 4 Department of Cell Biology and\nCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut, United States\nof America\n* sunil.hwang@carolinas.org\nAbstract\nThough the rhesus monkey is one of the most valuable non-human primate animal models\nfor various human diseases because of its manageable size and genetic and proteomic\nsimilarities with humans, proteomic research using rhesus monkeys still remains challeng-\ning due to the lack of a complete protein sequence database and effective strategy. To in-\nvestigate the most effective and high-throughput proteomic strategy, comparative data\nanalysis was performed employing various protein databases and search engines. The Uni-\nProt databases of monkey, human, bovine, rat and mouse were used for the comparative\nanalysis and also a universal database with all protein sequences from all available species\nwas tested. At the same time, de novo sequencing was compared to the SEQUEST search\nalgorithm to identify an optimal work flow for monkey proteomics. Employing the most effec-\ntive strategy, proteomic profiling of monkey organs identified 3,481 proteins at 0.5% FDR\nfrom 9 male and 10 female tissues in an automated, high-throughput manner. Data are\navailable via ProteomeXchange with identifier PXD001972. Based on the success of this al-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 25
encoding: FLOAT32
metadata:
{"title": "A Draft Map of Rhesus Monkey Tissue Proteome for Biomedical Research", "chroma:document": "ternative interpretation of MS data, the list of proteins identified from 12 organs of male and\nfemale subjects will benefit future rhesus monkey proteome research.\nIntroduction\nSince the human genome project was completed in 2003, proteomics has become a powerful\ntool for understanding the large and global characteristics of proteins within a broad range of\nbiomedical research platforms [1\u20133]. To achieve automated peptide sequencing using tandem\nmass spectrometry (MS/MS), development of database search algorithms such as SEQUEST,\nMascot and X!Tandem, have been geared toward the few species with well-annotated protein\ndatabases[4\u20137]. However, automated and high-throughput peptide sequencing with mass spec-\ntrometry analysis has been hindered for research in species with incomplete or uncertain\nPLOS ONE | DOI:10.1371/journal.pone.0126243\nMay 14, 2015\n1 / 18\nOPEN ACCESS\nCitation: Lee J-G, McKinney KQ, Lee Y-Y, Chung H-\nN, Pavlopoulos AJ, Jung KY, et al. (2015) A Draft\nMap of Rhesus Monkey Tissue Proteome for\nBiomedical Research. PLoS ONE 10(5): e0126243.\ndoi:10.1371/journal.pone.0126243\nAcademic Editor: Xuejiang Guo, Nanjing Medical\nUniversity, CHINA\nReceived: October 7, 2014\nAccepted: March 28, 2015\nPublished: May 14, 2015\nCopyright: \u00a9 2015 Lee et al. This is an open access\narticle distributed under the terms of the Creative\nCommons Attribution License, which permits\nunrestricted use, distribution, and reproduction in any\nmedium, provided the original author and source are\ncredited.\nData Availability Statement: These raw data are\navailable from http://proteomecentral.\nproteomexchange.org/cgi/GetDataset?ID=\nPXD001972.\nFunding: This research was supported by a\nCarolinas HealthCare System Cannon Research\nGrant (CRG 08-026). The funders had no role in\nstudy design, data collection and analysis, decision to\npublish, or preparation of the manuscript.\nCompeting Interests: The authors have declared\nthat no competing interests exist."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 26
encoding: FLOAT32
metadata:
{"title": "A draft map of the human proteome", "chroma:document": "ARTICLE\ndoi:10.1038/nature13302\nA draft map of the human proteome\nMin-Sik Kim1,2, Sneha M. Pinto3, Derese Getnet1,4, Raja Sekhar Nirujogi3, Srikanth S. Manda3, Raghothama Chaerkady1,2,\nAnil K. Madugundu3, Dhanashree S. Kelkar3, Ruth Isserlin5, Shobhit Jain5, Joji K. Thomas3, Babylakshmi Muthusamy3,\nPamela Leal-Rojas1,6, Praveen Kumar3, Nandini A. Sahasrabuddhe3, Lavanya Balakrishnan3, Jayshree Advani3, Bijesh George3,\nSantosh Renuse3, Lakshmi Dhevi N. Selvan3, Arun H. Patil3, Vishalakshi Nanjappa3, Aneesha Radhakrishnan3, Samarjeet Prasad1,\nTejaswini Subbannayya3, Rajesh Raju3, Manish Kumar3, Sreelakshmi K. Sreenivasamurthy3, Arivusudar Marimuthu3,\nGajanan J. Sathe3, Sandip Chavan3, Keshava K. Datta3, Yashwanth Subbannayya3, Apeksha Sahu3, Soujanya D. Yelamanchi3,\nSavita Jayaram3, Pavithra Rajagopalan3, Jyoti Sharma3, Krishna R. Murthy3, Nazia Syed3, Renu Goel3, Aafaque A. Khan3,\nSartaj Ahmad3, Gourav Dey3, Keshav Mudgal7, Aditi Chatterjee3, Tai-Chung Huang1, Jun Zhong1, Xinyan Wu1,2, Patrick G. Shaw1,\nDonald Freed1, Muhammad S. Zahari2, Kanchan K. Mukherjee8, Subramanian Shankar9, Anita Mahadevan10,11, Henry Lam12,\nChristopher J. Mitchell1, Susarla Krishna Shankar10,11, Parthasarathy Satishchandra13, John T. Schroeder14, Ravi Sirdeshmukh3,\nAnirban Maitra15,16, Steven D. Leach1,17, Charles G. Drake16,18, Marc K. Halushka15, T. S. Keshava Prasad3, Ralph H. Hruban15,16,\nCandace L. Kerr19{, Gary D. Bader5, Christine A. Iacobuzio-Donahue15,16,17, Harsha Gowda3 & Akhilesh Pandey1,2,3,4,15,16,20\nTheavailabilityofhumangenomesequencehastransformedbiomedicalresearchoverthepastdecade.However,anequiv-\nalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present\na draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic\nprofiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary hae-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 27
encoding: FLOAT32
metadata:
{"title": "A draft map of the human proteome", "chroma:document": "matopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting forapproximately 84% of the\ntotal annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis\nenabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding\nRNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based\nresource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to\naccelerate biomedical research in health and disease.\nAnalysis of the complete human genome sequence has thus far led to\ntheidentificationofapproximately20,687protein-codinggenes1,although\nthe annotation still continues to be refined. Mass spectrometryhas rev-\nolutionized proteomics studies in a manner analogous to the impact of\nnext-generationsequencingongenomicsandtranscriptomics2\u20134.Several\ngroups, including ours, have used mass spectrometry to catalogue com-\nplete proteomes of unicellular organisms5\u20137 and to explore proteomes\nofhigherorganisms,includingmouse8andhuman9,10.Todevelopadraft\nmapofthehumanproteomebysystematicallyidentifyingandannotat-\ning protein-coding genes in the human genome, we carried out prote-\nomic profiling of 30 histologically normal human tissues and primary\ncells using high-resolution mass spectrometry. We generated tandem\nmassspectracorrespondingtoproteinsencodedby17,294genes,account-\ning for approximately 84% of the annotated protein-coding genes in\nthehumangenome\u2014toourknowledgethelargestcoverageofthehuman\nproteomereportedsofar.Thisincludesmassspectrometricevidencefor\nproteins encoded by2,535genes that havenot been previously observed\nasevidencedbytheirabsenceinlarge community-based proteomic data\nsets\u2014PeptideAtlas11, GPMDB12 and neXtProt13 (which includes anno-\ntations from the Human Protein Atlas14).\nA general limitation of current proteomics methods is their depen-"}


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id: 28
encoding: FLOAT32
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{"title": "A draft map of the human proteome", "chroma:document": "dence on predefined protein sequence databases for identifying pro-\nteins. To overcome this, we also used a comprehensive proteogenomic\nanalysis strategy to identify novel peptides/proteins that are currently\nnot part of annotated protein databases. This approach revealed novel\nprotein-coding genes in the human genome that are missing from cur-\nrent genome annotations in addition to evidence of translation of several\nannotatedpseudogenesaswellasnon-codingRNAs.Asdiscussedbelow,\nwe provide evidence for revisinghundreds ofentries in protein databases\nbased on our data. This includes novel translationstart sites, gene/exon\nextensions and novel coding exons for annotated genes in the human\ngenome.\nGenerating a high-quality mass spectrometry data set\nTo generate a baseline proteomic profile in humans, we studied 30 his-\ntologicallynormalhumancellandtissuetypes,including17adulttissues,\n1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. 2Department of Biological Chemistry, Johns Hopkins University School of\nMedicine, Baltimore, Maryland 21205, USA. 3Institute of Bioinformatics, International Tech Park, Bangalore 560066, India. 4Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana\n70130, USA. 5The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. 6Department of Pathology, Universidad de La Frontera,Center of Genetic and Immunological Studies-Scientific\nand Technological Bioresource Nucleus, Temuco 4811230, Chile. 7School of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. 8Department of Neurosurgery,\nPostgraduate Institute of Medical Education & Research, Chandigarh 160012, India. 9Department of Internal Medicine Armed Forces Medical College, Pune 411040, India. 10Department of\nNeuropathology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India. 11Human Brain Tissue Repository, Neurobiology Research Centre, National Institute of Mental Health and"}


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id: 29
encoding: FLOAT32
metadata:
{"title": "A draft map of the human proteome", "chroma:document": "Neurosciences, Bangalore 560029, India. 12Department of Chemical and Biomolecular Engineering and Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear\nWater Bay, Hong Kong. 13Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India. 14Department of Medicine, Johns Hopkins University School of\nMedicine, Baltimore, Maryland 21224, USA. 15The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231,\nUSA. 16Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. 17Department of Surgery, Johns Hopkins University School of Medicine, Baltimore,\nMaryland 21231, USA. 18Departments of Immunology and Urology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.\n19Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine Baltimore, Maryland 21205, USA. 20Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana\n70130, USA. {Present address: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.\n2 9\nM A Y 2 0 1 4\n| V O L 5 0 9 |\nN A T U R E\n| 5 7 5\n\u00a92014 Macmillan Publishers Limited. All rights reserved"}


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id: 30
encoding: FLOAT32
metadata:
{"title": "A proteomic atlas of the legume, M. truncatula, and its nitrogen fixing endosymbiont, S. meliloti", "chroma:document": "A proteomic atlas of the legume, M. truncatula, and its nitrogen \nfixing endosymbiont, S. meliloti\nCatherine E. Minogue1,2, Harald Marx1,2, Dhileepkumar Jayaraman3, Alicia L. Richards2, \nNicholas W. Kwiecien2, Alireza F. Sihapirani4, Shanmugam Rajasekar3, Junko Maeda5, \nKevin Garcia5, Angel R. Del Valle-Echevarria5, Jeremy Volkening6, Michael S. Westphall2, \nSushmita Roy7,8, Michael R. Sussman6, Jean-Michel An\u00e93,5, Joshua J. Coon2,9,*\n1Co-first author\n2Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA\n3Department of Agronomy, University of Wisconsin-Madison, Madison, WI 53706, USA\n4Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA\n5Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA\n6Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA\n7Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, \nWI 53706, USA\n8Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA\n9Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, \nUSA\nAbstract\nLeguminous plants \u2018fix\u2019 atmospheric nitrogen through complex symbiotic relationships with \nrhizobial soil bacteria. These plants play a key role in agricultural sustainability because, unlike \nother major crops (e.g., corn, wheat and rice), they require no expensive and environmentally \ndeleterious fertilizer. Much like the fundamental and unique insights obtained from the study of \nplant pathogens, research on symbiotic bacteria and their host plants is providing new mechanistic \ninformation on plant growth and development. In this resource we describe a large-scale, \nquantitative proteomic study, which includes key post-translational modifications, to establish the \nfirst global proteomic blueprint of a legume and its rhizobial endosymbiont. By quantifying over \n*Corresponding author. jcoon@chem.wisc.edu.\nAuthor contributions"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 31
encoding: FLOAT32
metadata:
{"title": "A proteomic atlas of the legume, M. truncatula, and its nitrogen fixing endosymbiont, S. meliloti", "chroma:document": "H.M., C.E.M, D.J., J.M.A. and J.J.C. conceived and designed the study. D.J., S.R., J.M., provided the plant material. C.E.M, A.L.R. \nand M.S.W. performed the proteomics experiments. H.M. and C.E.M. analyzed the data. H.M., C.E.M., D.J., K.G. and A.R.D.E. \ninterpreted the data. N.W.K. and H.M. and built the website. A.F.S., J.V. and S.R. generated the regulatory network. The paper was \nwritten by C.E.M., H.M., D.J., M.R.S., K.G., A.R.D.E, J.M.A. and J.J.C. and was edited by all authors.\nAccession codes\nThe raw mass spectrometry data was submitted via ProteomeXchange (Vizca{\\\u2019{\\i}}no, J. A. et al., 2014) to the PRIDE repository \n(PXD002692) (Vizca{\\\u2019{\\i}}no, et al., 2013).\nSupplementary information\nSupplemental information includes seven figures and four tables and can be found with this article online.\nHHS Public Access\nAuthor manuscript\nNat Biotechnol. Author manuscript; available in PMC 2021 October 31.\nPublished in final edited form as:\nNat Biotechnol. 2016 November ; 34(11): 1198\u20131205. doi:10.1038/nbt.3681.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 32
encoding: FLOAT32
metadata:
{"title": "A Quantitative Proteome Map of the Human Body", "chroma:document": "A Quantitative Proteome Map of the Human Body\nLihua Jiang1,3, Meng Wang1,3, Shin Lin2, Ruiqi Jian1, Xiao Li1, Joanne Chan1, Guanlan \nDong1, Huaying Fang1, Aaron E. Robinson1, GTEx Consortium, Michael P. Snyder1,4,*\n1Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA\n2Division of Cardiology, University of Washington, Seattle, WA 98195, USA\n3These authors contributed equally\n4Lead Contact\nSUMMARY\nDetermining protein levels in each tissue and how they compare with RNA levels is important for \nunderstanding human biology and disease as well as regulatory processes that control protein \nlevels. We quantified the relative protein levels from over 12,000 genes across 32 normal human \ntissues. Tissue-specific or tissue-enriched proteins were identified and compared to transcriptome \ndata. Many ubiquitous transcripts are found to encode tissue-specific proteins. Discordance of \nRNA and protein enrichment revealed potential sites of synthesis and action of secreted proteins. \nThe tissue-specific distribution of proteins also provides an in-depth view of complex biological \nevents that require the interplay of multiple tissues. Most importantly, our study demonstrated that \nprotein tissue-enrichment information can explain phenotypes of genetic diseases, which cannot be \nobtained by transcript information alone. Overall, our results demonstrate how understanding \nprotein levels can provide insights into regulation, secretome, metabolism, and human diseases.\nGraphical Abstract\n*Correspondence: mpsnyder@stanford.edu.\nAUTHOR CONTRIBUTIONS\nL.J. led this project in generating proteomics data, data analysis, and manuscript preparation. M.W. developed statistical methods for \nproteomics data analysis and integration. S.L. performed the initial data analysis and SNP database construction. R.J. and J.C. did \nproteomics sample preparation and mass spectrometry data acquisition and contributed to making figures. X.L. did the analysis on the"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 33
encoding: FLOAT32
metadata:
{"title": "A Quantitative Proteome Map of the Human Body", "chroma:document": "association of tissue-enriched proteins to diseases. H.F. contributed to the discussion of data analysis. G.D. contributed to SNP and \nisoform early data analysis. A.R. did SNP peptide spectra library search. M.P.S. contributed to project supervision and manuscript \nreview and revision. All the authors contributed to manuscript revision.\nSUPPLEMENTAL INFORMATION\nSupplemental Information can be found online at https://doi.org/10.1016/j.cell.2020.08.036.\nDECLARATION OF INTERESTS\nM.P.S. is a cofounder and is on the scientific advisory board of Personalis, Filtircine, SensOmics, Qbio, January, Mirvie, Oralome, and \nProteus. He is also on the scientific advisory board (SAB) of Genapsys and Jupiter. The other authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nCell. Author manuscript; available in PMC 2021 October 01.\nPublished in final edited form as:\nCell. 2020 October 01; 183(1): 269\u2013283.e19. doi:10.1016/j.cell.2020.08.036.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 34
encoding: FLOAT32
metadata:
{"title": "A quest into the human brain", "chroma:document": "IMAGES: THE KAROLINSKA INSTITUTE WITH THE ALLEN INSTITUTE FOR BRAIN SCIENCE\nSPECIAL SECTION\nO\nur brain is composed of 86 billion neurons and a similar number \nof non-neuronal cells. The National Institute of Health\u2019s Brain Re-\nsearch through Advancing Innovative Neurotechnologies (BRAIN) \nInitiative - Cell Census Network (BICCN), which was \ufb01 rst launched \nin 2017, is a consortium of centers distributed in the United States \nand Europe that work together toward the goal of characterizing \ncell types and their functions in the brains of humans, nonhuman \nprimates (NHPs), and rodents.\nIn Science, Science Advances, and Science Translational Medi-\ncine, we present the results of this monumental eff ort. By leveraging the \nmost-advanced technologies, which, until now, were mostly applied to ani-\nmal models, the studies examine the cellular composition of the adult and \ndeveloping human brain at the transcriptional, epigenetic, and functional \nlevels. The studies are organized around \ufb01 ve main themes: (i) adult hu-\nman single-cell atlasing, including studies using single-cell transcriptomic \nand epigenomic analyses to characterize the human brain; (ii) adult NHP \nsingle-cell atlasing, which focuses on similar single-cell analyses in marmo-\nset and macaque brain; (iii) comparative single-cell analyses that compare \ncellular composition in human versus NHP brain; (iv) human and NHP \nbrain development single-cell analyses that focus on the characterization \nof developmental dynamics in developing human and NHP brain; and (iv) \nhuman neuronal cell-type functional and anatomical analysis and model-\ning, which includes the physiological and anatomical characterization of \ncellular properties in living human tissues, and the modeling of cell types \nand specialized cellular properties in humans versus rodent models.\nThe data collected by the BICCN will now allow researchers to tackle fun-\ndamental scienti\ufb01 c questions about the human brain and its genetic orga-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 35
encoding: FLOAT32
metadata:
{"title": "A quest into the human brain", "chroma:document": "nization. The era of cellular human brain research is knocking at our door! \n10.1126/science.adl0913\nThe background depicts three-\ndimensional renderings of \nreconstructed neurons obtained from \nliving brain slices. The diversity in \ncolor and shape represents the wide \nvariety of neuronal subtypes that \nmake up the human brain.\nBy Mattia Maroso\nPERSPECTIVE\nA family portrait of human brain cells  \np. 168\nRESEARCH ARTICLES\nInterindividual variation in human \ncortical cell type abundance and \nexpression  p. 170\nMolecular programs of regional \nspecifi cation and neural stem cell fate \nprogression in macaque telencephalon  \np. 171\nComprehensive cell atlas of the \nfi rst-trimester developing human brain  \np. 172\nSingle-cell analysis of prenatal and \npostnatal human cortical development  \np. 173\nSingle-cell DNA methylation and 3D \ngenome architecture in the human \nbrain  p. 174\nTranscriptomic diversity of cell types \nacross the adult human brain  \np. 175\nTranscriptomic cytoarchitecture \nreveals principles of human neocortex \norganization  p. 176\nSignature morphoelectric properties of \ndiverse GABAergic interneurons in the \nhuman neocortex  p. 177\nMorphoelectric and transcriptomic \ndivergence of the layer 1 interneuron \nrepertoire in human versus mouse \nneocortex  p. 178\nComparative transcriptomics reveals \nhuman-specifi c cortical features  \np. 179\nA comparative atlas of single-cell \nchromatin accessibility in the human \nbrain  p. 180\nSpatiotemporal molecular dynamics \nof the developing human thalamus  \np. 181\nRELATED ITEMS\nSCIENCE ADVANCES BRAIN CELL \nCENSUS SECTION \n10.1126/SCIADV.ADL0650\nSCIENCE TRANSLATIONAL MEDICINE \nRESEARCH ARTICLE BY AMENT ET AL. \n10.1126/SCITRANSLMED.ADE1283\nSCIENCE.ORG/COLLECTIONS/\nBRAIN-CELL-CENSUS\nA QUEST INTO THE  \nHUMAN BRAIN\n166    13 OCTOBER 2023 \u2022 VOL 382 ISSUE 6667\nscience.org  SCIENCE\nDownloaded from https://www.science.org on October 13, 2023"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 36
encoding: FLOAT32
metadata:
{"title": "Differential Changes in Functional Connectivity of Striatum-Prefrontal and Striatum-Motor Circuits in Premanifest Huntington\u0090s Disease", "chroma:document": "Research Article\nNeurodegener Dis\nDifferential Changes in Functional Connectivity \nof Striatum-Prefrontal and Striatum-Motor \nCircuits in Premanifest Huntington\u2019s Disease\nMartin Kronenbuerger a, b    Jun Hua c, d    Jee Y.A. Bang a, e    Kia E. Ultz a    Xinyuan Miao c, d    \nXiaoyu Zhang c, d    James J. Pekar c, d    Peter C.M. van Zijl c, d    Wenzhen Duan e, f    \nRussell L. Margolis e\u2013g    Christopher A. Ross e\u2013g    \na\n Division of Movement Disorders, Department of Neurology, Johns Hopkins University School of Medicine, \nBaltimore, MD, USA; b\n Department of Neurology, University Medicine Greifswald, Greifswald, Germany; c\n Department \nof Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; d\n F.M. Kirby Research Center for \nFunctional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; e\n Department of Psychiatry and Behavioral \nSciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; f\n Department of Neuroscience and \nPharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; g\n Department of Neurology,  \nJohns Hopkins University School of Medicine, Baltimore, MD, USA\nReceived: June 13, 2019\nAccepted: June 19, 2019\nPublished online: August 14, 2019\nMartin Kronenbuerger\nDepartment of Neurology, University of Greifswald\nFerdinand-Sauerbruch-Strasse\nDE\u201317475 Greifswald (Germany)\nE-Mail martin.kronenbuerger @ med.uni-greifswald.de\n\u00a9 2019 S. Karger AG, Basel\nE-Mail karger@karger.com\nwww.karger.com/ndd\nDOI: 10.1159/000501616\nKeywords\nFunctional connectivity \u00b7 Prefrontal cortex \u00b7 Chorea \u00b7 \nPremanifest period \u00b7 Magnetic resonance imaging, 7 T\nAbstract\nBackground: Huntington\u2019s disease (HD) is a progressive neu-\nrodegenerative disorder. The striatum is one of the first brain \nregions that show detectable atrophy in HD. Previous studies \nusing functional magnetic resonance imaging (fMRI) at 3 tes-\nla (3 T) revealed reduced functional connectivity between stri-\natum and motor cortex in the prodromal period of HD. Neu-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 37
encoding: FLOAT32
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{"title": "Differential Changes in Functional Connectivity of Striatum-Prefrontal and Striatum-Motor Circuits in Premanifest Huntington\u0090s Disease", "chroma:document": "roanatomical and neurophysiological studies have suggested \nsegregated corticostriatal pathways with distinct loops in-\nvolving different cortical regions, which may be investigated \nusing fMRI at an ultra-high field (7 T) with enhanced sensitiv-\nity compared to lower fields. Objectives: We performed fMRI \nat 7 T to assess functional connectivity between the striatum \nand several chosen cortical areas including the motor and \nprefrontal cortex, in order to better understand brain changes \nin the striatum-cortical pathways. Method: 13 manifest sub-\njects (age 51 \u00b1 13 years, cytosine-adenine-guanine [CAG]  \nrepeat 45 \u00b1 5, Unified Huntington\u2019s Disease Rating Scale  \n[UHDRS] motor score 32 \u00b1 17), 8 subjects in the close-to-onset \npremanifest period (age 38 \u00b1 10 years, CAG repeat 44 \u00b1 2, \nUHDRS motor score 8 \u00b1 2), 11 subjects in the far-from-onset \npremanifest period (age 38 \u00b1 11 years, CAG repeat 42 \u00b1 2,  \nUHDRS motor score 1 \u00b1 2), and 16 healthy controls (age 44 \u00b1 \n15 years) were studied. The functional connectivity between \nthe striatum and several cortical areas was measured by rest-\ning state fMRI at 7 T and analyzed in all participants. Results: \nCompared to controls, functional connectivity between stria-\ntum and premotor area, supplementary motor area, inferior \nfrontal as well as middle frontal regions was altered in HD (all \np values < 0.001). Specifically, decreased striatum-motor con-\nnectivity but increased striatum-prefrontal connectivity were \nfound in premanifest HD subjects. Altered functional connec-\nM.K. and J.H. contributed equally to this paper.\nDownloaded by: \nEast Carolina University - Laupus Library              \n150.216.68.200 - 8/19/2019 8:41:03 PM"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 38
encoding: FLOAT32
metadata:
{"title": "Immunocytological studies of lymph nodes in rheumatoid arthritis and malignant lymphoma", "chroma:document": "Annals of the Rheumatic Diseases, 1980, 39, 147-151\nImmunocytological studies of lymph nodes in\nrheumatoid arthritis and malignant lymphoma\nR. F. WILLKENS, GILBERT F. ROTH, GUNNAR HUSBY, AND\nR. C. WILLIAMS, JR.\nFrom the Department ofMedicine, Division ofArthritis, Harborview Medical Center, University of Washington\nSchool of Medicine, Seattle, Washington, USA, and the Department of Medicine, Bernalillo County Medical\nCenter, University ofNew Mexico School ofMedicine, Albuquerque, New Mexico 87131, Mexico\nSLTmmARY\nLymph nodes obtained from 9 patients with active rheumatoid arthritis were stained\nby immunological techniques permitting identification of B and T cell areas within the nodes. The\nlymph nodes were also compared with those obtained from patients with lymphoma. The rheumatoid\nlymph nodes showed prominent B cell staining in the follicular centres by the EAC and fluores-\nceinated immunoglobulin techniques. Interfollicular areas were intensely stained with anti-theta\nglobulin. In contrast, lymphoma nodes stained less intensely with fluoresceinated immunoglobulins\nbut stained like benign nodes with EAC. The difference in staining may reflect the degree of dis-\norganisation of the neoplastic follicle and/or the different sensitivity of these 2 methods in the\ndetection of B cells. The differences in staining are helpful in distinguishing the benign changes\nassociated with chronic inflammation from neoplastic B cell proliferative changes seen in lymph\nnodes.\nSome patients with rheumatoid arthritis (RA) have\nlymphadenopathy, and several histological studies\nhave been published on the lymph nodes from such\npatients.' 5 The histological similarity of nodes\nfrom rheumatoid arthritis and nodular lymphoma\nhas\noccasionally led\nto incorrect\ndiagnosis and\ninappropriate therapy.2 4 The present study com-\npared lymph nodes, and in some instances splenic\ntissues, from patients with RA and from patients\nwith malignant lymphoma, as well as normal lymph\nnodes. Particular attention was directed at identi-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 39
encoding: FLOAT32
metadata:
{"title": "Immunocytological studies of lymph nodes in rheumatoid arthritis and malignant lymphoma", "chroma:document": "fication of relative patterns of lymph node archi-\ntecture as well as the types of lymphoid cells present\nas identified by immunological techniques developed\nfor use with frozen tissue sections.6 7\nMaterials and methods\nPATIENTS STUDIED\nAxillary lymph nodes were obtained from 9 patients\nwith\nactive rheumatoid\narthritis.\nPatients\nwere\nclassified as definite or classical RA on the basis of\nAccepted for publication 23 August 1978\nCorrespondence to Robert F. Willkens, MD, Harborview\nMedical Center, 325 Ninth Avenue, Seattle, Washington\n98104, USA.\nTable 1\nCharacterisation ofpatients with rheumatoid\narthritis\nPatient\nDuration of ESR\nRF\nANA\nTherapy\ndisease\n(mm/h)\n(years)\n1\n20\n17\n1:64\npi\nGold2\n2\n5\n76\n1:5120\nN\nSteroids\n3\n21\n17\n1:320\nP\nGold\n4\n21\n6\n1:2080\nP\nGold,\nsteroids\n5\n13\n46\n1:1280\nN\nCytoxan\n6\n3\n62\nN\nN\n-\n7\n5\n11\nN\nP\nGold\n8\n7\n18\n1:512\nP\nGold\n9\n7\n16\n1:5120\nP\nGold,\nsteroids\niP-positive, N-negative.\n2A11 patients were on salicylates or another nonsteroidal anti-inflam-\nmatory drug in addition to drug(s) listed.\nARA criteria.8 An outline of age, sex, and clinical\nstatus of all studied patients is given in Table 1.\nFor comparison lymph nodes or spleen were\nobtained from 3 patients with lymphoma, and nor-\nmal lymph nodes were obtained from 3 subjects\nduring surgical procedures for nonmalignant con-\nditions. Mediastinal thymoma was obtained from 1\npatient for study.\n-47"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 40
encoding: FLOAT32
metadata:
{"title": "Adult hippocampal neurogenesis and its role in Alzheimer's disease", "chroma:document": "REVIEW\nOpen Access\nAdult hippocampal neurogenesis and its role in\nAlzheimer\u2019s disease\nYangling Mu* and Fred H Gage\nAbstract\nThe hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage at early stages\nof Alzheimer\u2019s disease (AD). Emerging evidence has indicated that altered neurogenesis in the adult hippocampus\nrepresents an early critical event in the course of AD. Although causal links have not been established, a variety of\nkey molecules involved in AD pathogenesis have been shown to impact new neuron generation, either positively\nor negatively. From a functional point of view, hippocampal neurogenesis plays an important role in structural\nplasticity and network maintenance. Therefore, dysfunctional neurogenesis resulting from early subtle disease\nmanifestations may in turn exacerbate neuronal vulnerability to AD and contribute to memory impairment,\nwhereas enhanced neurogenesis may be a compensatory response and represent an endogenous brain repair\nmechanism. Here we review recent findings on alterations of neurogenesis associated with pathogenesis of AD,\nand we discuss the potential of neurogenesis-based diagnostics and therapeutic strategies for AD.\nKeywords: Alzheimer\u2019s disease, adult neurogenesis, hippocampus, neural stem cell\nIntroduction\nAlzheimer\u2019s disease (AD), first described by the German\nneuropathologist Alois Alzheimer as Dementia Praecox\nin 1907, is an age-related neurodegenerative disease\ncharacterized by progressive loss of memory and dete-\nrioration of cognitive functions. Individuals with the dis-\norder usually experience difficulties in learning,\nperformance speed, recall accuracy and/or problem sol-\nving [1]. The gradual intraneuronal accumulation of\nneurofibrillary tangles formed as a result of abnormal\nhyperphosphorylation of cytoskeletal tau protein, extra-\ncellular deposition of amyloid-b (Ab) protein as senile\nplaques, and massive neuronal death represent impor-\ntant neuropathological hallmarks of AD [2]. These"}


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id: 41
encoding: FLOAT32
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{"title": "Adult hippocampal neurogenesis and its role in Alzheimer's disease", "chroma:document": "pathologies are evident in specific, vulnerable brain\nareas and the hippocampus is one of the earliest to be\naffected [3]. The hippocampus is a mammalian brain\nstructure that lies under the medial temporal lobe, with\none on each side of the brain. Although there is a lack\nof consensus relating to terms describing the hippocam-\npus and its adjacent cortex, the term hippocampus or\nhippocampal formation generally applies to the dentate\ngyrus (DG), the hippocampus proper - composed of\nCA1, CA2 and CA3 fields - and the subiculum. The\norganization of the hippocampal circuitry has been tra-\nditionally characterized as a unidirectional, trisynaptic\nexcitatory pathway (reviewed in [4]). Briefly, the entorh-\ninal cortex (EC) provides the main source of input to\nthe hippocampus through connections to the DG. Infor-\nmation flow then proceeds from DG to CA3 to CA1. In\nturn, CA1 projects to the subiculum and sends the hip-\npocampal output back to the deep layers of EC. Beha-\nvioral studies have long suggested that the hippocampus\nplays a critical role in learning and memory [5], which\ndepend on functional and structural changes occurring\nin the hippocampus, such as long-term potentiation\n(LTP) and synaptic remodeling [6,7]. The discovery of a\nde novo production of neurons in the adult DG has\nintroduced the possibility of a new form of plasticity\nthat could sustain memory processes. A growing body\nof evidence supports the view that promotion of adult\nhippocampal neurogenesis improves pattern separation\nand spatial memory [8,9]. In contrast, a decline in neu-\nrogenesis may underlie cognitive impairments associated\nwith aging and disorders such as AD [10,11]. Interest-\ningly, increasing evidence shows that central molecular\nplayers in AD influence the generation of new\n* Correspondence: ymu@salk.edu\nLaboratory of Genetics, the Salk Institute for Biological Studies, La Jolla, CA\n92037, USA\nMu and Gage Molecular Neurodegeneration 2011, 6:85\nhttp://www.molecularneurodegeneration.com/content/6/1/85"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 42
encoding: FLOAT32
metadata:
{"title": "Adult hippocampal neurogenesis and its role in Alzheimer's disease", "chroma:document": "\u00a9 2011 Mu and Gage; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative\nCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and\nreproduction in any medium, provided the original work is properly cited."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 43
encoding: FLOAT32
metadata:
{"title": "Marcaje colin\u00e9rgico en la corteza cerebral y el hipocampo en algunas especies animales y su relaci\u00f3n con la enfermedad de Alzheimer", "chroma:document": "C\u00f3mo\n citar\n este\n art\u00edculo:\n Orta-Salazar\n E,  et\n al.\n Marcaje\n colin\u00e9rgico\n en\n la\n corteza\n cerebral\n y  el\n hipocampo\n en\n algunas\nespecies\n animales\n y  su\n relaci\u00f3n\n con\n la\n enfermedad\n de\n Alzheimer.\n Neurolog\u00eda.\n 2014.\n doi:10.1016/j.nrl.2012.10.007\nARTICLE IN PRESS\n+Model\nNRL-432;\n \nNo.\n of\n Pages\n 7\nNeurolog\u00eda.\n 2014;xxx(xx):xxx\u2014xxx\nNEUROLOG\u00cdA\nwww.elsevier.es/neurologia\nREVISI\u00d3N\nMarcaje\n colin\u00e9rgico\n en  la  corteza\n cerebral\n y  el  hipocampo\n en\nalgunas\n especies\n animales\n y su  relaci\u00f3n  con  la enfermedad\nde\n Alzheimer\nE.\n Orta-Salazar a, C.A.\n Cuellar-Lemus a, S. D\u00edaz-Cintra b y\n A.I.\n Feria-Velasco a,\u2217\na Centro\n Universitario\n de\n Ciencias\n Biol\u00f3gicas\n y\n Agropecuarias\n (CUCBA),\n Universidad\n de\n Guadalajara,\n Zapopan,\n M\u00e9xico\nb Instituto\n de\n Neurobiolog\u00eda\n (INB),\n Campus\n UNAM-Juriquilla,\n Juriquilla,\n Quer\u00e9taro,\n M\u00e9xico\nRecibido\n el\n 24\n de\n septiembre\n de\n 2012;\n aceptado\n el\n 4\n de\n octubre\n de\n 2012\nPALABRAS\n CLAVE\nInervaci\u00f3n\ncolin\u00e9rgica;\nColina\nacetiltransferasa;\nAcetilcolinesterasa;\nCorteza\n cerebral;\nHipocampo;\nEnfermedad\n de\nAlzheimer\nResumen\nIntroducci\u00f3n:\n El\n sistema\n colin\u00e9rgico\n incluye\n neuronas\n localizadas\n en\n el\n cerebro\n basal\n anterior\ny\n sus\n axones\n largos\n proyectan\n a\n la\n corteza\n cerebral\n e\n hipocampo.\n Este\n sistema\n modula\n la\n funci\u00f3n\ncognitiva.\n En\n la\n enfermedad\n de\n Alzheimer\n (EA)\n y  en\n el\n proceso\n de\n envejecimiento\n la\n disfunci\u00f3n\ncolin\u00e9rgica\n hay\n una\n asociaci\u00f3n\n entre\n el\n deterioro\n cognitivo\n y\n el\n da\u02dcno\n progresivo\n de\n las\n \ufb01bras\ncolin\u00e9rgicas,\n lo\n que\n conduce\n al\n postulado\n de\n la\n hip\u00f3tesis\n colin\u00e9rgica.\nDesarrollo:\n En\n la\n EA\n se\n producen\n alteraciones\n en\n la\n expresi\u00f3n\n y\n en\n la\n actividad\n de\n la\n colina\nacetiltransferasa\n (ChAT)\n y\n la\n acetilcolinesterasa\n (AChE),\n enzimas\n espec\u00ed\ufb01cas\n relacionadas\n con\n la\nfunci\u00f3n\n del\n SC.\n Ambas\n prote\u00ednas\n juegan\n un\n papel\n importante\n en\n la\n transmisi\u00f3n\n colin\u00e9rgica\n mos-\ntrando\n variaciones\n en\n la\n corteza\n cerebral\n y  en\n el\n hipocampo,\n tanto\n por\n el\n envejecimiento,\n como\npor\n la\n EA."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 44
encoding: FLOAT32
metadata:
{"title": "Marcaje colin\u00e9rgico en la corteza cerebral y el hipocampo en algunas especies animales y su relaci\u00f3n con la enfermedad de Alzheimer", "chroma:document": "la\n EA.\n En\n ambas\n estructuras,\n los\n des\u00f3rdenes\n demenciales\n est\u00e1n\n asociados\n a\n la\n destrucci\u00f3n\nsevera\n y\n desorganizaci\u00f3n\n de\n las\n proyecciones\n colin\u00e9rgicas\n que\n se\n encuentran\n afectadas.\n Para\nel\n estudio\n de\n este\n sistema\n se\n han\n usado\n marcadores\n espec\u00ed\ufb01cos\n como\n los\n anticuerpos\n contra\nChAT\n y\n AChE\n que\n han\n sido\n empleados\n en\n las\n t\u00e9cnicas\n de\n inmuhistoqu\u00edmica\n de\n luz\n y\n micro-\nscopia\n electr\u00f3nica\n en\n algunas\n especies\n animales.\nConclusiones:\n En\n este\n trabajo\n se\n hace\n una\n revisi\u00f3n\n de\n los\n principales\n estudios\n inmunomorfo-\nl\u00f3gicos\n de\n la\n corteza\n cerebral\n e\n hipocampo\n de\n varias\n especies\n animales\n con\n \u00e9nfasis\n en\n el\n SC\n y\nsu\n relaci\u00f3n\n con\n la\n EA.\n\u00a9\n 2012\n Sociedad\n Espa\u02dcnola\n de\n Neurolog\u00eda.\n Publicado\n por\n Elsevier\n Espa\u00f1a,\n S.L.\n Todos\n los\n derechos\nreservados.\nKEYWORDS\nCholinergic\ninnervation;\nCholinergic\n markers\n in\n the\n cortex\n and\n hippocampus\n of  some\n animal\n species\n and\n their\ncorrelation\n to\n Alzheimer\u2019s\n disease\nAbstract\nIntroduction:\n The\n cholinergic\n system\n includes\n neurons\n located\n in\n the\n basal\n forebrain\n and\ntheir\n long\n axons\n that\n reach\n the\n cerebral\n cortex\n and\n the\n hippocampus.\n This\n system\n modulates\n\u2217 Autor\n para\n correspondencia.\nCorreo\n electr\u00f3nico:\n alfredoferia1340@hotmail.com\n (A.I.\n Feria-Velasco).\n0213-4853/$\n \u2013  see\n front\n matter\n \u00a9\n 2012\n Sociedad\n Espa\u02dcnola\n de\n Neurolog\u00eda.\n Publicado\n por\n Elsevier\n Espa\u00f1a,\n S.L.\n Todos\n los\n derechos\n reservados.\ndoi:10.1016/j.nrl.2012.10.007"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 45
encoding: FLOAT32
metadata:
{"title": "Comprehensive identification of peptides in tandem mass spectra using an efficient open search engine", "chroma:document": "nature biotechnology   advance online publication \n1\nb r i e f  c o m m u n i c at i o n s\n1Key Laboratory of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing, China. 2University \nof Chinese Academy of Sciences, Beijing, China. 3National Institute of Biological Sciences, Beijing, Beijing, China. 4State Key Laboratory of Proteomics, Beijing \nProteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China. 5State Key Laboratory of Biocontrol and \nGuangdong Provincial Key Laboratory of Plant Resources, College of Ecology and Evolution, Sun Yat-Sen University, Guangzhou, China. 6These authors contributed \nequally to this work. Correspondence should be addressed to S.-M.H. (smhe@ict.ac.cn) or H.C. (chihao@ict.ac.cn).\nReceived 3 December 2017; accepted 3 August 2018; published online 8 October 2018; doi:10.1038/nbt.4236\nMatching tandem mass (MS/MS) spectra to peptide sequences  \ncontained in databases has long been the dominant approach for \nshotgun proteomics. However, >50% of spectra go unmatched1. One \nreason for this is that the current restricted search engines cannot \nidentify peptides with unexpected modifications2\u20135. Another is that \nsemi- and nonspecific digestion, in-source fragmentation, and cof-\nragmentation of coeluting peptides6,7, collectively referred to as the \n\u2018dark matter\u2019 of shotgun proteomics8,9, hinder peptide identification. \nOpen search engines enlarge the search space with more types of \nmodifications to retrieve more peptide candidates, but these are very \ntime consuming, and it is still difficult to reliably identify >50% of \nthe spectra1,9.\nWe developed a computationally efficient search engine, Open-\npFind, that improves peptide and protein identification by matching \nMS/MS spectra to a substantially expanded search space. Open-\npFind consists of two search steps: one open and one restricted \n(Supplementary Fig. 1). First, a sequence-tag-based strategy is used"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 46
encoding: FLOAT32
metadata:
{"title": "Comprehensive identification of peptides in tandem mass spectra using an efficient open search engine", "chroma:document": "to match spectra to a much larger set of possible peptide sequences \nin the open search (Fig. 1a). Based on these open search results, a \nrestricted search is then performed in which several key parameters, \nincluding modification types and protein sequence entries, are auto-\nmatically set by semi-supervised machine learning.\ncomprehensive identification \nof peptides in tandem mass \nspectra using an efficient open \nsearch engine\nHao Chi1,2,6 , Chao Liu1,2,6, Hao Yang1,2,6, Wen-Feng Zeng1,2, \nLong Wu1,2, Wen-Jing Zhou1,2, Rui-Min Wang1,2,  \nXiu-Nan Niu1,2, Yue-He Ding3, Yao Zhang4,5, \nZhao-Wei Wang1,2, Zhen-Lin Chen1,2, Rui-Xiang Sun1,2, \nTao Liu1, Guang-Ming Tan1, Meng-Qiu Dong3 ,  \nPing Xu4, Pei-Heng Zhang1 & Si-Min He1,2\nWe present a sequence-tag-based search engine, Open-pFind, \nto identify peptides in an ultra-large search space that includes \ncoeluting peptides, unexpected modifications and digestions. \nOur method detects peptides with higher precision and speed \nthan seven other search engines. Open-pFind identified  \n70\u201385% of the tandem mass spectra in four large-scale \ndatasets and 14,064 proteins, each supported by at least two \nprotein-unique peptides, in a human proteome dataset. \nWe compared the performance of Open-pFind with that of seven \nother search engines using a 15N/13C metabolically labeled dataset \n(Dong-Ecoli-QE; Supplementary Tables 1 and 2 and Supplementary \nFig. 2). Open-pFind identified 50.5% more peptide-spectrum matches \n(PSMs), 11.3% more distinct peptides and 6.9% more distinct peptide \nsequences than the second-best search engine (Fig. 1b) at a peptide-\nlevel false discovery rate (FDR) of 1%. Here, a distinct peptide is \ndefined by its amino acid sequence and all of its modifications, and a \ndistinct peptide sequence is defined by just its amino acid sequence. \nOf the PSMs identified by Open-pFind, 54.9% were obtained from \nthe restricted search space (Fig. 1c), whereas 45.1% were obtained \nfrom the extended search space produced by semi-tryptic/nonspecific"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 47
encoding: FLOAT32
metadata:
{"title": "Comprehensive identification of peptides in tandem mass spectra using an efficient open search engine", "chroma:document": "digestions, unexpected modifications (including mutations), coelut-\ning peptides and the combination of these factors.\nThe Dong-Ecoli-QE dataset was mainly used to evaluate search \nengine precision (Supplementary Fig. 3), which was measured by the \nfraction of correct results among all of the results reported. Given the \ndesign of this dataset, if a PSM identification is estimated to be correct \nfor an unlabeled peptide, the corresponding precursor ions with 15N \nor 13C labeling should generally be observed in full mass scans and \nvalid quantitation ratios should be obtained. For an unlabeled peptide, \nif the corresponding labeled precursor ion is not observed, which \nresults in an invalid or not-a-number quantitation ratio (reported \nas the NaN ratio by pQuant10), then the corresponding PSM is more \nlikely to be incorrect. Generally, a smaller percentage of NaN ratio \nresults indicates higher precision, and precision can be estimated \nindependently of the target-decoy approach via the percentage of \nNan ratio results (Supplementary Note 1).\nWe started with PSMs assigned to either unmodified peptides or \npeptides with four common modifications (cysteine carbamidometh-\nylation, methionine oxidation, N-terminal glutamine-to-pyroglutamic \nacid conversion and protein N-terminal acetylation; Supplementary \nTable 3 and Supplementary Fig. 4). The percentage of NaN ratio \nresults was <1% for PSMs consistently identified by both Open-pFind \nand every other search engine in the paired comparison (Fig. 1d). \nThis confirms that the PSMs identified consistently by different search \nengines are more credible. For PSMs uniquely identified by Open-\npFind, the percentage with a NaN ratio remained at ~1%, whereas this \npercentage rose to >10% for the majority of PSMs uniquely identified \nby other search engines. Similar results were obtained when the same \nanalysis was performed on another metabolically labeled dataset (Xu-\nYeast-QEHF; Supplementary Fig. 5). We then examined all of the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 48
encoding: FLOAT32
metadata:
{"title": "Comprehensive identification of peptides in tandem mass spectra using an efficient open search engine", "chroma:document": "PSMs, without excluding any modifications. The percentage of PSMs \nwith NaN ratio results increased substantially for open search engines \n(Supplementary Fig. 6). Even in this context, the Open-pFind results \nhad the second smallest percentage of NaN ratio PSMs, second only \nto pFind, indicating that the PSMs from the extended search space of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 49
encoding: FLOAT32
metadata:
{"title": "Cytology, architecture, development, and connections of the primate striatum: Hints for human pathology", "chroma:document": "Neurobiology of Disease 176 (2023) 105945\nAvailable online 5 December 2022\n0969-9961/\u00a9 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).\nCytology, architecture, development, and connections of the primate \nstriatum: Hints for human pathology \nNatalia L\u00b4opez-Gonz\u00b4alez del Rey a,b, Miguel \u00b4Angel Garc\u00eda-Cabezas a,c,* \na PhD Program in Neuroscience UAM-Cajal; Madrid, Spain \nb HM CINAC (Centro Integral de Neurociencias Abarca Campal). Hospital Universitario HM Puerta del Sur. HM Hospitales. Madrid, Spain \nc Departamento de Anatom\u00eda, Histolog\u00eda y Neurociencia, Facultad de Medicina, Universidad Aut\u00b4onoma de Madrid; Madrid, Spain   \nA R T I C L E  I N F O   \nKeywords: \nStriatum \nBasal ganglia \nNucleus accumbens \nCaudate \nPutamen \nCerebral cortex \nCortical type \nMyelin \nPlasticity \nNeurodegeneration \nA B S T R A C T   \nDegeneration of neurons and circuits across the striatum shows stereotyped time-course and spatial topography \npatterns that are distinct for Huntington\u2019s disease, Parkinson\u2019s disease, or the Tauopathies. These patterns of \nneurodegeneration in humans have not yet been systematically related to developmental, connectional, cellular, \nand chemical factors studied in human and non-human primates, that may underlie potential differences in \nselective vulnerability across striatal sectors. Relating primate anatomy to human pathology could provide new \nvenues for identifying molecular, cellular, and connectional factors linked to the degeneration of striatal neurons \nand circuits. This review describes and summarizes several developmental, cellular, structural, and connectional \nfeatures of the primate striatum in relation to patterns of neurodegeneration in the striatum of humans and of \nnon-human primate models. We review (1) the types of neurons in the primate striatum, (2) the cyto-, myelo-, \nand chemoarchitecture of the primate striatum, (3) the developmental origin of the striatum in light of modern"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 50
encoding: FLOAT32
metadata:
{"title": "Cytology, architecture, development, and connections of the primate striatum: Hints for human pathology", "chroma:document": "patterning studies, (4) the organization of corticostriatal projections in relation to cortical types, and (5) the \ntopography and time-course of neuron loss, glial reaction, and protein aggregation induced by neurodegenerative \ndiseases in humans and in non-human primate models across striatal sectors and their corresponding cortical \nareas. We summarize current knowledge about key aspects of primate striatal anatomy and human pathology and \nindicate knowledge gaps that should be addressed in future studies. We aim to identify factors for selective \nvulnerability to neurodegeneration of striatal neurons and circuits and obtain hints that could help elucidate \nstriatal pathology in humans.   \n1. Introduction \nStriatal neurons and their circuits are involved in several neurode-\ngenerative diseases, chiefly Parkinson\u2019s and Huntington\u2019s diseases (Rub \net al., 2016; Singh et al., 2016), but also Alzheimer\u2019s disease, fronto-\ntemporal dementia, and tangle-predominant dementia (Suenaga et al., \n1990; Halabi et al., 2013; Kawakami et al., 2014). Degeneration of \nneurons and circuits across the striatum is not random; on the contrary, \nit shows stereotyped time-course and spatial topography patterns that \nare distinct for each neurodegenerative disease. In spite of such distinct \npatterns of degeneration, the cytological, connectional, developmental, \nand chemical factors that may underlie potential differences of selective \nvulnerability have not been systematically described across striatal \nsectors in relation to spatial topography and time-course of \nneurodegenerative pathology. This approach would provide new venues \nfor identifying molecular, cellular, and connectional factors linked to the \nselective degeneration of striatal neurons and circuits. \nIn this review we describe and summarize several developmental, \ncellular, structural, and connectional features of the primate striatum in \nrelation to patterns of neurodegeneration across striatal sectors in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 51
encoding: FLOAT32
metadata:
{"title": "Cytology, architecture, development, and connections of the primate striatum: Hints for human pathology", "chroma:document": "humans with neurodegenerative diseases and in non-human primate \nmodels of neurodegeneration. We review (1) the types of neurons that \npopulate the primate striatum and their participation in basal ganglia \ncircuits, (2) the cyto-, myelo-, and chemoarchitecture of the primate \nstriatum, (3) the embryonic development of the striatum in light of \nmodern studies of subpallial patterning, neurogenesis, and morpho-\ngenesis, (4) the organization of corticostriatal projections in relation to \ncortical types revealed by synaptic tract-tracing studies in non-human \n* Corresponding author at: Departamento de Anatom\u00eda, Histolog\u00eda y Neurociencia, Facultad de Medicina, Universidad Aut\u00b4onoma de Madrid, Calle Arzobispo \nMorcillo 4, 28029 Madrid, Spain. \nE-mail address: garcia.cabezas@uam.es (M.\u00b4A. Garc\u00eda-Cabezas).  \nContents lists available at ScienceDirect \nNeurobiology of Disease \njournal homepage: www.elsevier.com/locate/ynbdi \nhttps://doi.org/10.1016/j.nbd.2022.105945 \nReceived 4 May 2022; Received in revised form 19 November 2022; Accepted 3 December 2022"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 52
encoding: FLOAT32
metadata:
{"title": "Design and Analysis Issues in Quantitative Proteomics Studies", "chroma:document": "Statistical Tools \n42\nPractical Proteomics 1/2007\n\u00a9 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim \nwww.practical.proteomics-journal.com\nDesign and Analysis Issues \nin Quantitative Proteomics \nStudies\nNatasha A. Karp and \nKathryn S. Lilley\nIntroduction\nProteomics is the study of \u2018the entire protein complement \nexpressed by a genome in a cell or tissue type\u2019, and is a ma-\njor tool in the post-genomics era [1]. Quantitative proteomics \nis the comparison of distinct proteomes (e.g. control versus \ntreatment or control versus disease) to identify protein spe-\ncies with changes in expression or post-translational state.  \nThere are now numerous different methods to interrogate \nthe proteome in a quantitative manner. Simplistically, these \nfall into two major categories; methods based around 2D gel \nelectrophoresis (2-DE) with post staining [2, 3] or pre-label-\nling [4, 5], or methodologies where quanti\ufb01 cation occurs us-\ning mass spectrometric measurement, for example stable \nisotope labelling, both in vitro [6\u20138] or in vivo [9], and label-\nfree approaches [10, 11].  Whichever method is employed, \nafter de\ufb01 ning the biological question to be answered by the \nstudy under consideration, an experimental design is then \nformulated. This design will include the methodologies to \nDOI 10.1002/pmic.200700683\n  Department of Biochemistry, \n Cambridge University, Cambridge, UK\n Dr. Kathryn Lilley\n University of Cambridge,\n Department of Biochemistry,\n Cambridge System Biology Centre,\n Tennis Court Road,\n Cambridge CB2 1QR, UK\n Fax: +44-1223-760255\n k.s.lilley@bioc.cam.ac.uk\nAbbreviations:\nFDR, false discovery rate\nFWER, family wise error rate\nPCER, per comparison error rate\nQuantitative proteomics is the comparison of \ndistinct proteomes which enables the iden-\nti\ufb01 cation of protein species which exhibit \nchanges in expression or post-translational \nstate in response to a given stimulus. Many \ndifferent quantitative techniques are being \nutilized and generate large datasets. Inde-\npendent of the technique used, these large"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 53
encoding: FLOAT32
metadata:
{"title": "Design and Analysis Issues in Quantitative Proteomics Studies", "chroma:document": "datasets need robust data analysis to ensure \nvalid conclusions are drawn from such stud-\nies.  Approaches to address the problems that \narise with large datasets are discussed to give \ninsight into the types of statistical analyses of \ndata appropriate for the various experimental \nstrategies that can be employed by quantita-\ntive proteomic studies.  This review also high-\nlights the importance of employing a robust \nexperimental design and highlights various is-\nsues surrounding the design of experiments. \nThe concepts and examples discussed within \nwill show how robust design and analysis \nwill lead to con\ufb01 dent results that will ensure \nquantitative proteomics delivers."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 54
encoding: FLOAT32
metadata:
{"title": "Amyloid in osteoarthritic hip joints: deposits in relation to chonodromatosis, pyrophosphate, and inflammatory cell infiltrate in the synovial membrane and fibrous capsule", "chroma:document": "Annals ofthe Rheumatic Diseases, 1983, 42, 659-664\nAmyloid in osteoarthritic hip joints: deposits in\nrelation to chondromatosis, pyrophosphate, and\ninflammatory cell infiltrate in the synovial membrane\nand fibrous capsule\nCHR. LADEFOGED\nFrom the Institute ofPathology, Odense University Hospital, Odense, Denmark\nSUMMARY\nThe relationship between osteoarthritic change and amyloid degeneration was studied\nin 116 joint capsules from osteoarthritic hip joints. Twenty-seven (23%) contained amyloid\ndeposits. Twenty-eight joint capsules showed chondroid metaplasia in the fibrous part. Signifi-\ncantly more amyloid degeneration was found among these. Six joint capsules contained pyro-\nphosphate crystals. Five of these were positive for amyloid. Chronic inflammation of the joint\ncapsule was found in 80 % of the cases and was negatively correlated with amyloid degeneration,\nwhich is in good agreement with the biphasic theory for the pathogenesis of amyloid. Further\ninvestigation is necessary to decide how chondroid metaplasia takes part in the production of\namyloid.\nIn 1972 Christensen and S0rensen' published 17\ncases of amyloid degeneration in hip joint capsules.\nThe cases were from an unselected series consisting\nof 43 patients operated on for severe osteoarthritis\ncoxae (46 capsules). This seems to be the first histo-\nlogical\ninvestigation\nof the\ncorrelation\nbetween\namyloidosis and osteoarthritis.\nThis paper describes amyloid deposits in the fi-\nbrous part of the capsule from osteoarthritic hip\njoints\nin\nrelation\nto secondary\nchondromatosis,\npyrophosphate\ndeposits,\nand\ninflammatory\ncell\ninfiltration.\nMaterial and methods\nThe\nmaterial\nfor\nlight\nmicroscopy\ncomprised\napproximately 5 x 3 x 2 cm pieces of tissue from the\nsynovial membrane and the fibrous capsule. They\nwere removed at each of 1 16 consecutive operations\nfor osteoarthritis coxae. Four patients had their hips\nresected bilaterally.\nThe average age of the patients was 61 years (range\n32-74), and 47 of them were women. None had"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 55
encoding: FLOAT32
metadata:
{"title": "Amyloid in osteoarthritic hip joints: deposits in relation to chonodromatosis, pyrophosphate, and inflammatory cell infiltrate in the synovial membrane and fibrous capsule", "chroma:document": "clinical signs of primary amyloidosis, myelomatosis,\nor\ntuberculosis.\nOne\npatient\nhad\nconcurrent\nAccepted for publication 9 November 1982.\nCorrespondence\nto Dr C. Ladefoged,\nInstitute\nof Pathology,\nSonderborg Hospital, 6400 Sonderborg, Denmark.\nrheumatoid arthritis. The operations were carried\nout according to the method of Chamley at the\ndepartment\nof Orthopaedic\nSurgery\n0,\nof\nthe\nOdense University Hospital.\nThe control material consisted of tissue from 25\nautopsy hip joint capsules without osteoarthritic\nchanges such as hyaline degeneration, vascular pro-\nliferation with perivascular fibrosis, inflammatory\ncell infiltration, chondroid metaplasia, or calcifica-\ntion. No macroscopic signs of osteoarthritis were\nseen on the femoral heads. The average age of the\npatients was 67 years, and 13 capsules were from\nwomen.\nNo\ncases\nof\ngeneralised\namyloidosis,\nrheumatoid arthritis, tuberculosis, or myelomatosis\nwere found in the control material.\nThe tissue was immediately fixed in 10% formalin\nand kept in it for approximately 24 hours. Thereafter\nrepresentative pieces were removed from both the\nsynovial membrane and the fibrous capsule and\nembedded in paraffin after dehydration in ethanol\nand xylene. Sections 6 gm thick were then stained\nwith haematoxylin and eosin, alcian blue 8GX,\nalkaline Congo red, and,\nin selected cases, van\nGieson's connective tissue stain. Amyloid was con-\nsidered to be specifically demonstrated when the\nyellowish-red colour of the alkaline Congo red stain-\ning showed green dichroism on polansation micros-\ncopy.3\nElectron microscopy was performed only on the\n659"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 56
encoding: FLOAT32
metadata:
{"title": "Cell transcriptomic atlas of the non-human primate Macaca fascicularis", "chroma:document": "Nature | Vol 604 | 28 April 2022 | 723\nArticle\nCell transcriptomic atlas of the non-human \nprimate Macaca fascicularis\nLei Han1,2,3,36, Xiaoyu Wei1,4,36, Chuanyu Liu1,2,3,36, Giacomo Volpe5,36, Zhenkun Zhuang1,6,36, \nXuanxuan Zou1,4,36, Zhifeng Wang1,2,36, Taotao Pan1,2, Yue Yuan1,4, Xiao Zhang7, Peng Fan7, \nPengcheng Guo7, Yiwei Lai8, Ying Lei1,2,3, Xingyuan Liu7, Feng Yu8, Shuncheng Shangguan9, \nGuangyao Lai9, Qiuting Deng1,4, Ya Liu1,2, Liang Wu1,2,4, Quan Shi1,10, Hao Yu1, Yunting Huang1,11, \nMengnan Cheng1,4, Jiangshan Xu1,4, Yang Liu1,4, Mingyue Wang1, Chunqing Wang1,4, \nYuanhang Zhang1,4, Duo Xie1,4, Yunzhi Yang12, Yeya Yu12, Huiwen Zheng12, Yanrong Wei12, \nFubaoqian Huang1,6, Junjie Lei1,4, Waidong Huang1,4, Zhiyong Zhu1,4, Haorong Lu1,11, Bo Wang1,11, \nXiaofeng Wei1,11, Fengzhen Chen1,11, Tao Yang1,11, Wensi Du1,11, Jing Chen1,11, Shibo Xu13, \nJuan An8,14, Carl Ward8, Zongren Wang15, Zhong Pei16, Chi-Wai Wong17, Xiaolei Liu7, \nHuafeng Zhang18, Mingyuan Liu7, Baoming Qin19, Axel Schambach20,21, Joan Isern22, \nLiqiang Feng23, Yan Liu13, Xiangyu Guo24,25, Zhen Liu26, Qiang Sun26, Patrick H. Maxwell27, \nNick Barker28, Pura Mu\u00f1oz-C\u00e1noves29, Ying Gu1, Jan Mulder30,31, Mathias Uhlen30,31, Tao Tan32, \nShiping Liu1,2,3, Huanming Yang1,33, Jian Wang1,33, Yong Hou1,2,3,12\u2009\u2709, Xun Xu1,2,12,34\u2009\u2709, \nMiguel A. Esteban7,8,35\u2009\u2709 & Longqi Liu1,2,3,12\u2009\u2709\nStudying tissue composition and function in non-human primates (NHPs) is crucial to \nunderstand the nature of our own species. Here we present a large-scale cell \ntranscriptomic atlas\u00a0that encompasses over 1 million cells from 45 tissues of the adult \nNHP Macaca fascicularis. This dataset provides a vast annotated resource to study a \nspecies phylogenetically close to humans. To demonstrate the utility of the atlas, we \nhave reconstructed the cell\u2013cell interaction networks that drive Wnt signalling across \nthe body, mapped the distribution of receptors and co-receptors for viruses causing \nhuman infectious diseases, and intersected our data with human genetic disease"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 57
encoding: FLOAT32
metadata:
{"title": "Cell transcriptomic atlas of the non-human primate Macaca fascicularis", "chroma:document": "orthologues to establish potential clinical associations. Our M.\u2009fascicularis cell atlas \nconstitutes an essential reference for future studies in humans and NHPs.\nA major obstacle to building a comprehensive human cell atlas1 is \nobtaining a full range of \u2018high-quality\u2019 samples of sufficient size. Given \ntheir evolutionary proximity, non-human primates (NHPs) represent \nthe nearest-to-human alternative. Generating an NHP cell atlas (NHPCA) \nwould produce a catalogue of features that could be used to study \nhuman physiology, disease and ageing. It would also provide insights \ninto the evolutionary mechanisms underlying different body function \nbetween NHPs and humans.\nNHPs comprise a large and diverse group of species with major \necological, dietary, locomotor and behavioural differences2. Because \nof their characteristics, including a more frequent reproductive \ncycle and wide availability, macaques, in particular Macaca fas-\ncicularis (also known as cynomolgus, crab-eating or long-tailed \nmonkey), are now used for research purposes worldwide3. Here we \nused adult M.\u2009fascicularis tissues to generate the largest NHP cell \ntranscriptomic dataset thus far. To facilitate exploration of this \nhttps://doi.org/10.1038/s41586-022-04587-3\nReceived: 11 March 2021\nAccepted: 23 February 2022\nPublished online: 13 April 2022\n Check for updates\n1BGI-Shenzhen, Shenzhen, China. 2BGI-Beijing, Beijing, China. 3Shenzhen Bay Laboratory, Shenzhen, China. 4College of Life Sciences, University of Chinese Academy of Sciences, Beijing, \nChina. 5Hematology and Cell Therapy Unit, IRCCS\u2013Istituto Tumori \u2018Giovanni Paolo II\u2019, Bari, Italy. 6School of Biology and Biological Engineering, South China University of Technology, \nGuangzhou, China. 7State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 58
encoding: FLOAT32
metadata:
{"title": "Cell transcriptomic atlas of the non-human primate Macaca fascicularis", "chroma:document": "University, Changchun, China. 8Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. 9Joint School of Life \nSciences, Guangzhou Institutes of Biomedicine and Health and Guangzhou Medical University, Guangzhou, China. 10Department of Biology, University of Copenhagen, Copenhagen, Denmark. \n11China National GeneBank, BGI-Shenzhen, Shenzhen, China. 12BGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China. 13Institute \nfor Stem Cells and Neural Regeneration, School of Pharmacy, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. 14University of Science and \nTechnology of China, Hefei, China. 15Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 16Department of Neurology, First Affiliated Hospital, Sun Yat-sen \nUniversity, Guangzhou, China. 17Huazhen Biosciences, Guangzhou, China. 18Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. 19Laboratory of Metabolism \nand Cell Fate, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. 20Institute of Experimental Hematology, Hannover Medical School, \nHannover, Germany. 21Division of Hematology/Oncology, Harvard Medical School, MA, Boston, USA. 22Spanish National Center for Cardiovascular Research (CNIC), Madrid, Spain. 23State Key \nLaboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. 24Jinan University, Guangzhou, China. 25Hubei Topgene \nBiotechnology Co., Ltd, Wuhan, China. 26Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain \nScience and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. 27Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 59
encoding: FLOAT32
metadata:
{"title": "Cell transcriptomic atlas of the non-human primate Macaca fascicularis", "chroma:document": "Cambridge, UK. 28A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore. 29Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), ICREA and \nCIBERNED, Barcelona, Spain. 30Department of Protein Science, Science for Life Laboratory, KTH\u2013Royal Institute of Technology, Stockholm, Sweden. 31Department of Neuroscience, Karolinska \nInstitute, Stockholm, Sweden. 32State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, \nChina. 33James D. Watson Institute of Genome Sciences, Hangzhou, China. 34Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, China. 35Institute of Stem Cells and \nRegeneration, Chinese Academy of Sciences, Beijing, China. 36These authors contributed equally: Lei Han, Xiaoyu Wei, Chuanyu Liu, Giacomo Volpe, Zhenkun Zhuang, Xuanxuan Zou,  \nZhifeng Wang. \u2709e-mail: houyong@genomics.cn; xuxun@genomics.cn; miguel@gibh.ac.cn; liulongqi@genomics.cn"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 60
encoding: FLOAT32
metadata:
{"title": "Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor", "chroma:document": "ARTICLE\nOPEN\nPrenatal stress modulates HPA axis homeostasis of offspring\nthrough dentate TERT independently of glucocorticoids\nreceptor\nMeng-Ying Liu1,2,8, Lu-Lu Wei1,8, Xian-Hui Zhu1,3,8, Hua-Chen Ding\n4,8, Xiang-Hu Liu1, Huan Li5,6, Yuan-Yuan Li3, Zhou Han1,2,\nLian-Di Li1, Zi-Wei Du1, Ya-Ping Zhou1, Jing Zhang1, Fan Meng1, Yu-Lin Tang3, Xiao Liu6\u2709, Chun Wang4\u2709 and Qi-Gang Zhou\n1,3,4,7\u2709\n\u00a9 The Author(s) 2022\nIn response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are\nreleased by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in\nthe hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the\nhomeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in\nadulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without\nhippocampal GR de\ufb01ciency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the\ndevelopmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability\nof the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of\nglucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the \ufb01rst exon of mouse Tert gene accounted for TERT\nde\ufb01ciency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism\nunderlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for\nmaintaining HPA axis homeostasis.\nMolecular Psychiatry (2023) 28:1383\u20131395; https://doi.org/10.1038/s41380-022-01898-9\nINTRODUCTION\nMaternal exposure to stresses during pregnancy reprograms the"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 61
encoding: FLOAT32
metadata:
{"title": "Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor", "chroma:document": "hypothalamic\u2013pituitary\u2013adrenal (HPA) axis of the offspring [1, 2].\nThe HPA axis is a critical adaptive system of the body for facing\nwith urgently physical and psychological challenges [3]. Although\nacute or short-term activation of the HPA axis is bene\ufb01cial for\nreacting to stimuli, chronic or long-term activation causes harmful\neffects [4]. It has been well-documented over the last 40 years that\nhyperactivity of the HPA axis is highly associated with the\npathology of adolescents\u2019 depression [4]. Maternal stress-induced\nexcessive glucocorticoids cross the placenta, impairing fetal HPA\ndevelopment and changing the HPA axis activity balance in the\noffspring [5\u20139]. However, the molecular mechanism underlying\nthe gestational stress-induced fetal HPA axis dysfunction remains\nlargely unknown.\nThe hippocampus is a major component exerting inhibitory\nmodulation of the activity of the paraventricular nucleus (PVN) in\nthe hypothalamus, playing an important role in maintaining the\nhomeostasis of the HPA axis [10\u201312]. The endogenous receptor for\nglucocorticoids, glucocorticoid receptor (GR), is a widely expressed\nnuclear hormone receptor in the brain, with the highest density in\nthe hippocampus [13, 14]. Activation of hippocampal GR exerts\nnegative feedback modulation of the HPA axis activity by inhibiting\nthe expression of corticotropinreleasing factor or hormone (CRF or\nCRH) in the PVN region, consequently causing decreased secretion\nof glucocorticoids from the adrenal cortex [11]. Decreased number\nand/or impaired function of the GR have been reported in patients\nwith depression in clinic [15, 16]. Preclinical studies suggest that the\ndysfunction of GR in the PFC and hippocampus are involved in the\nchronic stress-induced attenuation of the negative feedback\n[17, 18]. The decreased expression and impaired function of GR\nare also implicated in the prenatal stress-caused elevated HPA\naxis reactivity in the offspring [7, 19, 20]. Accumulating evidences\nsupport the hypothesis that the impairment of the central stress"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 62
encoding: FLOAT32
metadata:
{"title": "Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor", "chroma:document": "hormone negative regulation system is causally involved in the\ndevelopment of depression [21]. However, a challenging question is\nwhether there is a mechanism beyond GR for maintaining the\nhomeostasis of the HPA axis in depression?\nTelomerase are composed of the highly conserved catalytic\ntelomerase reverse transcriptase (TERT), the telomerase RNA\nReceived: 24 May 2020 Accepted: 18 November 2022\nPublished online: 8 December 2022\n1State Key Laboratory of Reproductive Medicine, Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China. 2Department of\nPharmacy, The Af\ufb01liated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. 3Department of Clinical Pharmacy, Sir Run Run Hospital, Nanjing Medical\nUniversity, Nanjing, China. 4Department of Psychiatry, Af\ufb01liated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China. 5School of Applied Science, Temasek\nPolytechnic, Singapore, Singapore. 6College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China. 7The Key Center of Gene Technology Drugs of Jiangsu Province,\nNanjing Medical University, Nanjing, China. 8These authors contributed equally: Meng-Ying Liu, Lu-Lu Wei, Xian-Hui Zhu, Hua-Chen Ding. \u2709email: liuxiao04_0@163.com;\nfm51109@163.com; qigangzhou@njmu.edu.cn\nwww.nature.com/mp\nMolecular Psychiatry\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 63
encoding: FLOAT32
metadata:
{"title": "Circulating Levels of Sex Steroid Hormones and Gastric Cancer", "chroma:document": "ARTICLE IN PRESS \nJID: ARCMED \n[mNS; March 26, 2021;21:0 ] \nArchives of Medical Research xxx (xxxx) xxx \nCirculating Levels of Sex Steroid Hormones and Gastric Cancer \nYelda A. Leal, a , \u2217 Minkyo Song, b Jovanny Zabaleta, c Gilberto Medina-Escobedo, d Patrick Caron, e \nAurelio Lopez-Colombo, f Chantal Guillemette, e and M. Constanza Camargo b \na Centro Institucional de Capacitaci\u00f3n y Registro de C\u00e1ncer, Unidad M\u00e9dica de Alta Especialidad (UMAE), Centro M\u00e9dico Nacional \"Ignacio Garc\u00eda \nT\u00e9llez,\u201d Instituto Mexicano de Seguro Social (IMSS), M\u00e9rida, Yucat\u00e1n, M\u00e9xico \nb Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA \nc Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA \nd Departamento de Patolog\u00eda, UMAE, Centro M\u00e9dico Nacional \"Ignacio Garc\u00eda T\u00e9llez,\" IMSS, M\u00e9rida, Yucat\u00e1n, M\u00e9xico \ne Pharmacogenomics Laboratory, Centre Hospitalier de l\u2019Universite Laval de Quebec, Research Center and Faculty of Pharmacy, Laval University, \nQuebec City, Quebec, Canada \nf UMAE, Centro M\u00e9dico Nacional \u201cManuel \u00c1vila Camacho,\u201d IMSS, Puebla, Puebla, M\u00e9xico \nReceived for publication August 26, 2020; accepted March 4, 2021 (ARCMED_2021_2647). \nAbstract \nBackground and Aims. Men develop gastric cancer more frequently than women, yet \nlittle is known about the mechanisms underlying this sex difference. Sex steroid hor- \nmones may in\ufb02uence gastric cancer risk. We therefore assessed whether major circulat- \ning adrenal precursors, androgens and estrogens were associated with gastric cancer in \na high-risk Mexican population. \nMethods. Blood samples were collected at time of diagnosis from 50 noncardia gastric \ncancer patients and 50 histologically con\ufb01rmed non-atrophic gastritis controls. Serum \nlevels of estradiol, testosterone and dehydroepiandrosterone (DHEA) measured with a \nvalidated mass spectrometry method were categorized in tertiles as low (T1), middle"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 64
encoding: FLOAT32
metadata:
{"title": "Circulating Levels of Sex Steroid Hormones and Gastric Cancer", "chroma:document": "(T2), and high (T3). Unconditional logistic regression models were used to calculate \nodds ratios (ORs) and 95% con\ufb01dence intervals (CI), adjusting for age, sex, and edu- \ncation. \nResults. Levels of DHEA were inversely associated with gastric cancer ( p -trend per \ntertile increase: < 0.0001), with adjusted ORs (95% CI) of T2 and T3 (vs. T1) of 0.25 \n(0.09\u20130.70) and 0.10 (0.03\u20130.34), respectively. Levels of estradiol and testosterone were \nnot signi\ufb01cantly associated with gastric cancer. \nConclusions. Our study provides evidence that higher concentration of circulating DHEA \nmay be associated with lower risk of noncardia gastric cancer. Longitudinal studies are \nneeded to evaluate the temporality of this association and investigate mechanisms of \ndisease pathogenesis. \u00a9 2021 Instituto Mexicano del Seguro Social (IMSS). Published \nby Elsevier Inc. All rights reserved. \nKey Words: Androgens, Dehydroepiandrosterone, DHEA, Gastric cancer, Estrogens, Estradiol, \nTestosterone. \nAddress reprint requests to: Yelda A. Leal, Centro Institucional de \nCapacitaci\u00f3n y Registro de C\u00e1ncer, Unidad M\u00e9dica de Alta Especiali- \ndad, Centro M\u00e9dico Nacional \u201cIgnacio Garc\u00eda T\u00e9llez\u201d, Instituto Mexicano \nde Seguro Social, M\u00e9rida, Yucat\u00e1n, M\u00e9xico. Tel: + 52 999-285-69-71; \nE-mail: yelda_leal03@yahoo.com.mx or yelda.leal@imss.gob.mx \nIntroduction \nGastric cancer is the third most common cause of death \nfrom cancer globally ( 1 ). Noncardia gastric cancer arises \nthrough a multistep process of chronic in\ufb02ammation initi- \nated by Helicobacter pylori infection: non-atrophic gastri- \ntis, multifocal atrophic gastritis, intestinal metaplasia, dys- \nplasia, and invasive adenocarcinoma ( 2 ). Notably, for most \n0188-4409/$ - see front matter. Copyright \u00a9 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved. \nhttps://doi.org/10.1016/j.arcmed.2021.03.001"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 65
encoding: FLOAT32
metadata:
{"title": "Circulating Levels of Sex Steroid Hormones and Gastric Cancer", "chroma:document": "Please cite this article as: Leal et al. , Circulating Levels of Sex Steroid Hormones and Gastric Cancer, Archives of Medical Research, https://doi.org/ \n10.1016/j.arcmed.2021.03.001"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 66
encoding: FLOAT32
metadata:
{"title": "Environmental enteric dysfunction: gut and microbiota adaptation in pregnancy and infancy", "chroma:document": "Environmental enteric dysfunction: gut and microbiota \nadaptation in pregnancy and infancy\nCarrie A. Cowardin1, Sana Syed1,2, Najeeha Iqbal2, Zehra Jamil2, Kamran Sadiq2, Junaid \nIqbal2, Syed Asad Ali2, Sean R. Moore1\n1Division of Paediatric Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, \nChild Health Research Center, University of Virginia, Charlottesville, VA, USA.\n2Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.\nAbstract\nEnvironmental enteric dysfunction (EED) is a subclinical syndrome of intestinal inflammation, \nmalabsorption and barrier disruption that is highly prevalent in low- and middle-income countries \nin which poverty, food insecurity and frequent exposure to enteric pathogens impair growth, \nimmunity and neurodevelopment in children. In this Review, we discuss advances in our \nunderstanding of EED, intestinal adaptation and the gut microbiome over the \u2018first 1,000 days\u2019 \nof life, spanning pregnancy and early childhood. Data on maternal EED are emerging, and they \nmirror earlier findings of increased risks for preterm birth and fetal growth restriction in mothers \nwith either active inflammatory bowel disease or coeliac disease. The intense metabolic demands \nof pregnancy and lactation drive gut adaptation, including dramatic changes in the composition, \nfunction and mother-to-child transmission of the gut microbiota. We urgently need to elucidate \nthe mechanisms by which EED undermines these critical processes so that we can improve global \nstrategies to prevent and reverse intergenerational cycles of undernutrition.\nIntroduction\nIn low- and middle-income countries (LMICs), maternal stunting is a risk factor for \nlow birthweight and subsequent childhood stunting, thereby perpetuating a vicious \nintergenerational cycle of undernutrition. This cycle has adverse consequences for children\u2019s \nsurvival, growth and neurodevelopment1. Maternal gut function during pregnancy is critical"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 67
encoding: FLOAT32
metadata:
{"title": "Environmental enteric dysfunction: gut and microbiota adaptation in pregnancy and infancy", "chroma:document": "to healthy fetal and child development2, asdemonstrated by studies of other enteropathies \nsuch as coeliac disease and inflammatory bowel disease. Environmental enteric dysfunction \nReprints and permissions information is available at www.nature.com/reprints.\nCorrespondence should be addressed to Sean R. Moore. sean.moore@virginia.edu.\nAuthor contributions\nS.R.M. and C.A.C. researched data for the article, made a substantial contribution to discussion of content, wrote the article, and \nreviewed/edited the manuscript before submission. S.S., N.I., Z.J. and J.I. researched data for the article, wrote the article, and \nreviewed/edited the manuscript before submission. K.S. wrote the article and reviewed/edited the manuscript before submission. \nS.A.A. researched data for the article, made a substantial contribution to discussion of content, and reviewed/edited the manuscript \nbefore submission.\nCompeting interests\nS.R.M. was a paid consultant for Takeda on paediatric short bowel syndrome in 2020. S.R.M. receives royalties from UpToDate for a \nchapter entitled \u201cPersistent diarrhoea in children in resource-limited countries\u201d. The other authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nNat Rev Gastroenterol Hepatol. Author manuscript; available in PMC 2023 October 01.\nPublished in final edited form as:\nNat Rev Gastroenterol Hepatol. 2023 April ; 20(4): 223\u2013237. doi:10.1038/s41575-022-00714-7.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 68
encoding: FLOAT32
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{"title": "Conservation, acquisition, and functional impact of sex-biased gene expression in mammals", "chroma:document": "Conservation, acquisition, and functional impact of sex-biased \ngene expression in mammals\nSahin Naqvi1,2, Alexander K. Godfrey1,2, Jennifer F. Hughes1, Mary L. Goodheart1,3, \nRichard N. Mitchell4, David C. Page1,2,3,*\n1Whitehead Institute, Cambridge MA 02142\n2Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139\n3Howard Hughes Medical Institute, Whitehead Institute, Cambridge MA 02142\n4Brigham and Women\u2019s Hospital, Harvard Medical School, Boston MA 02115\nAbstract\nSex differences abound in human health and disease, as in other mammals employed as models. \nUnknown is the extent to which sex differences are conserved at the molecular level across species \nand tissues. We surveyed sex differences in gene expression in human, macaque, mouse, rat, and \ndog, across 12 tissues. In each tissue, we identified hundreds of genes with conserved sex-biased \nexpression \u2013 findings that, combined with genomic analyses of human height, explain ~12% of the \ndifference in height between females and males. We surmise that conserved sex biases in \nexpression of genes otherwise operating equivalently in females and males contribute to sex \ndifferences in traits. However, most sex-biased expression arose during the mammalian radiation, \nsuggesting careful attention to interspecies divergence when modeling human sex differences.\nOne sentence summary:\nRNA sequencing of twelve tissues in five species reveals conservation, acquisition, and the \nfunctional impact of sex-biased gene expression.\nMales and females exhibit differences across a wide range of biological processes. Studies in \nhumans have documented sex differences in anthropometric traits (1), energy metabolism \n(2), brain morphology (3), and immune (4) and cardiac (5) function. Sex differences are also \nevident in the incidence, prevalence, and mortality across diseases, including autoimmune \ndisorders (6), cardiovascular diseases (7), and autism (8). Beyond humans, sex differences"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
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{"title": "Conservation, acquisition, and functional impact of sex-biased gene expression in mammals", "chroma:document": "are common in other mammals, many of which are models of sex-biased human traits and \ndiseases (9). For example, males are larger than females in most mammalian species (10), \n*Correspondence to: dcpage@wi.mit.edu.\nAuthor contributions: S.N., A.K.G, J.F.H., and D.C.P. designed the study. J.F.H. procured cyno tissue samples. M.L.G. procured \nmouse and rat tissue samples, with assistance from S.N. S.N. processed tissue samples and performed computational analyses, with \nassistance from A.K.G. R.N.M. performed histological evaluations on human tissue sections. D.C.P. supervised work. S.N. and D.C.P. \nwrote the paper.\nData and code availability: Raw RNA sequencing data (.fastq files) have been deposited in the Gene Expression Omnibus (accession \nnumber GSE125483). Processed data (expression count/TPM matrices and sample metadata) and code required to reproduce the \nanalyses are available at http://pagelab.wi.mit.edu/page/papers/Naqvi_et_al_2019 and at Zenodo (doi: 10.5281/zenodo.2658829).\nHHS Public Access\nAuthor manuscript\nScience. Author manuscript; available in PMC 2019 December 06.\nPublished in final edited form as:\nScience. 2019 July 19; 365(6450): . doi:10.1126/science.aaw7317.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 70
encoding: FLOAT32
metadata:
{"title": "Construction of a human cell landscape at single-cell level", "chroma:document": "Nature | www.nature.com | 1\nArticle\nConstruction of a human cell landscape at \nsingle-cell level\nXiaoping Han1,2,19\u2009\u2709, Ziming Zhou1,19, Lijiang Fei1,19, Huiyu Sun1,19, Renying Wang1,19, Yao Chen3,19, \nHaide Chen1,4,19, Jingjing Wang1,4,19, Huanna Tang5, Wenhao Ge6, Yincong Zhou7, Fang Ye1, \nMengmeng Jiang1, Junqing Wu1, Yanyu Xiao1, Xiaoning Jia8, Tingyue Zhang1, Xiaojie Ma9,  \nQi Zhang10, Xueli Bai10, Shujing Lai1, Chengxuan Yu1, Lijun Zhu6, Rui Lin11, Yuchi Gao12,  \nMin Wang13, Yiqing Wu3, Jianming Zhang14, Renya Zhan15, Saiyong Zhu9, Hailan Hu8, \nChangchun Wang16, Ming Chen7, He Huang2,17,18, Tingbo Liang10, Jianghua Chen5,  \nWeilin Wang6, Dan Zhang3 & Guoji Guo1,2,4,17,18\u2009\u2709\nSingle-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex \nsystems1. However, a comprehensive single-cell atlas has not been achieved for \nhumans. Here we use single-cell mRNA sequencing to determine the cell-type \ncomposition of all major human organs and construct a scheme for the human cell \nlandscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have \nnot been well characterized. We established a \u2018single-cell HCL analysis\u2019 pipeline that \nhelps to define human cell identity. Finally, we performed a single-cell comparative \nanalysis of landscapes from human and mouse to identify conserved genetic \nnetworks. We found that stem and progenitor cells exhibit strong transcriptomic \nstochasticity, whereas differentiated cells are more distinct. Our results provide a \nuseful resource for the study of human biology.\nIndividual cells are fundamental units of life. Breakthroughs in \nsingle-cell mRNA sequencing have greatly enhanced our ability \nto identify the transcriptomes of individual types of cell2\u20135. Using \nhigh-throughput barcoding strategies, it is now possible to profile thou-\nsands of single cells at the same time6,7. These methods have allowed \nthe mapping of cell atlases for whole organisms8\u201315. For example, cell \natlases for the mammalian system have been generated by analysing"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 71
encoding: FLOAT32
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{"title": "Construction of a human cell landscape at single-cell level", "chroma:document": "both fetal and adult mouse tissues16\u201319. Despite extensive efforts in \ndissecting the cellular compositions of various human tissues20\u201332, to \nour knowledge a comprehensive cell landscape for humans has not \nbeen achieved.\nConstructing an HCL using microwell-seq\nMicrowell-seq is a cost-effective single-cell mRNA sequencing technol-\nogy that offers advantages over existing technologies in doublet rate \nand cell-type compatibility16. Sequencing titration experiments and \ncross-platform comparison suggest that this method can robustly \ndetect rare populations even at low sequencing depth (Supplementary \nTable\u00a01, Extended Data Fig.\u00a01a). Using microwell-seq, we embarked \nupon the creation of a basic landscape of major human cell types using \nsamples from a Chinese Han population. Donated tissues were per-\nfused or washed and prepared as single-cell suspensions using specific \nprotocols (Supplementary Table\u00a01). Our analyses included samples of \nboth fetal and adult tissue and covered 60 human tissue types (two to \nfour replicates per tissue type in general; Extended Data Fig.\u00a01b). We \nalso analysed seven types of cell culture, including induced pluripotent \nstem (iPS) cells, embryoid body cells, haematopoietic cells derived from \nco-cultures of human H9 and mouse OP9 cells33, and pancreatic beta \ncells derived from H9 cells using a seven-stage protocol34(Extended \nData Fig.\u00a01b). Single cells were processed using microwell-seq16 and \nsequenced at around 3,000 reads per cell; data were then processed \nusing published pipelines35 (Fig.\u00a01a). Altogether, 702,968 single cells \npassed our quality control tests (Supplementary Table\u00a01).\nIn a global view, the complete human tissue data set is grouped into \n102 major clusters (Fig.\u00a01b; Supplementary Table\u00a02). Multiple tissues, \nincluding artery, trachea, pleura, omentum, oesophagus and fallopian \ntube, contributed to the defined adult stromal/mesenchymal cells, \nsuch as cluster 4 (C4), C18, C27, and C70. Other clusters with substantial"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 72
encoding: FLOAT32
metadata:
{"title": "Construction of a human cell landscape at single-cell level", "chroma:document": "multi-tissue contributions correspond to fetal stromal cells (C7, C10, \nC17, C19, C21, C64, and C72), endothelial cells (C8, C20, C29, and C66), \nmacrophages (C2, C51, C69, and C78), and fetal epithelial cells (C1) \nhttps://doi.org/10.1038/s41586-020-2157-4\nReceived: 23 October 2018\nAccepted: 12 March 2020\nPublished online: 25 March 2020\n Check for updates\n1Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China. 2Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang \nUniversity School of Medicine, Hangzhou, China. 3Department of Reproductive Endocrinology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, China. 4Zhejiang \nProvincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr.\u00a0Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Hangzhou, China. 5Kidney Disease Center, \nThe First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 6Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University \nSchool of Medicine, Hangzhou, China. 7College of Life Sciences, Zhejiang University, Hangzhou, China. 8Center for Neuroscience, Zhejiang University School of Medicine, Hangzhou, China. \n9Life Sciences Institute, Zhejiang University, Hangzhou, China. 10Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, \nHangzhou, China. 11Hangzhou Repugene Technology, Hangzhou, China. 12Annoroad Gene Technology, Beijing, China. 13Veritas Genetics Asia, Hangzhou, China. 14Department of Neurosurgery, \nThe Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 15Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, \nHangzhou, China. 16Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 73
encoding: FLOAT32
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{"title": "Construction of a human cell landscape at single-cell level", "chroma:document": "Hospital, Hangzhou, China. 17Institute of Hematology, Zhejiang University, Hangzhou, China. 18Stem Cell Institute, Zhejiang University, Hangzhou, China. 19These authors contributed equally: \nXiaoping Han, Ziming Zhou, Lijiang Fei, Huiyu Sun, Renying Wang, Yao Chen, Haide Chen, Jingjing Wang. \u2709e-mail: xhan@zju.edu.cn; ggj@zju.edu.cn"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 74
encoding: FLOAT32
metadata:
{"title": "The potential role of opioid vaccines and monoclonal antibodies in the opioid overdose crisis", "chroma:document": "The potential role of opioid vaccines and monoclonal antibodies \nin the opioid overdose crisis\nSuky Martineza, Hannah Harrisa, Thomas Chaob, Rachel Lubaa, Marco Pravetonic, Sandra \nD Comera, Jermaine D Jonesa\naDivision on Substance Use Disorders, Columbia University Irving Medical Center & New York \nState Psychiatric Institute, New York, NY, USA\nbBehavioural Reward Affect + Impulsivity Neuroscience Lab, Faculty of Medicine, the University of \nBritish Columbia, Vancouver, Bc, Canada\ncDepartment of Psychiatry and Behavioral Sciences, University of Washington School of \nMedicine, Seattle, WA, USA\nKeywords\nOpioids; overdose; opioid vaccines; monoclonal antibodies; immunotherapies\n1. The need for continued development of medications to treat opioid \noverdose\nSince the late 1990s, the U.S. has experienced an exponential increase in opioid-related \noverdose deaths and made substantial economic expenditures to address the harms \nassociated with opioid use disorder (OUD) [1,2]. As the epidemic has evolved, we have \nobserved a substantial increase in the detection of potent, illicitly manufactured fentanyls \nin opioid drug supplies as well as in cocaine and methamphetamine drug supplies, and \nwithin counterfeit pills sold as oxycodone, benzodiazepines, and other prescription drugs. \nThis has led to increases in the rates of opioid-related overdose among those with OUD and \namong those who are not traditionally at risk such as psychostimulant users and recreational \nCONTACT Suky Martinez, suky.martinez@nyspi.columbia.edu, Division on Substance Use Disorders, Columbia University Irving \nMedical Center, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. \nDeclaration of interests\nWithin the past three years, JD Jones received compensation (in the form of partial salary support) and has served as a paid \nconsultant to Alkermes and the World Health Organization. Within the past three years, SD Comer has received research funding from"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 75
encoding: FLOAT32
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{"title": "The potential role of opioid vaccines and monoclonal antibodies in the opioid overdose crisis", "chroma:document": "Alkermes, BioXcel Therapeutics, Corbus, Go Medical, Intra-cellular Therapies, Janssen, and Lyndra. SD Comer has also consulted \nfor: Alkermes, Clinilabs, Opiant, and Otsuka, and she has received honoraria from the World Health Organization. SD. Comer is \nalso the recipient of NIH funding to study opioid vaccines and monoclonal antibodies. M Pravetoni has filed patents disclosing the \ncomposition and methods of use of vaccines and monoclonal antibodies for substance use disorders. Dr. Pravetoni is also the recipient \nof NIH funding to study opioid vaccines and monoclonal antibodies.\nThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or \nfinancial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.\nReviewer disclosures\nPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.\nHHS Public Access\nAuthor manuscript\nExpert Opin Investig Drugs. Author manuscript; available in PMC 2023 June 06.\nPublished in final edited form as:\nExpert Opin Investig Drugs. 2023 March ; 32(3): 181\u2013185. doi:10.1080/13543784.2023.2187286.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 76
encoding: FLOAT32
metadata:
{"title": "Deciphering the human phosphoproteome", "chroma:document": "news & views\nPROTEOMICS\nDeciphering the human phosphoproteome\nMachine learning provides a functional score for ~120,000 human phosphorylation sites.\nGiulia Franciosa, Ana Martinez-Val and Jesper V. Olsen\nS\nite-specific protein phosphorylation \nis one of the most important post-\ntranslational modifications that \ncells use to modulate their signaling \npathways. To study signaling networks \nat a systems-wide scale, the method of \nchoice is mass spectrometry (MS)-based \nphosphoproteomics1. Tens of thousands \nof phosphorylation sites can be routinely \nidentified in a single experiment, but \nfunctional interpretation of these sites \nremains challenging2. In this issue, Ochoa \net\u00a0al.3 apply a machine learning approach to \npublic datasets and construct a functional \nlandscape of the human phosphoproteome. \nTheir results will help phosphoproteomics \nresearchers to prioritize phosphorylation \nsites from large-scale datasets according to \nbiological relevance.\nA few minutes after a cell receives a \nsignaling cue, such as stimulation by a \ngrowth factor, thousands of phosphosites \non its signaling proteins are phosphorylated \nor dephosphorylated, altering the \nproteins\u2019 activity, subcellular localization, \nprotein\u2013protein interactions or stability1. \nPhosphorylation is added by protein kinases \nand removed by phosphatases.  \nThis interplay is tightly controlled in healthy \ncells, and its breakdown is associated with \ndiseases such as cancer and metabolic \ndisorders, making kinases prominent drug \ntargets for the pharmaceutical industry4.\nIn MS-based phosphoproteomics, \nproteins are first digested into peptides. As \nphosphorylation is a low-stoichiometric \nmodification, phosphopeptides in the \nsample are first enriched, and then analyzed \nby liquid chromatography and tandem mass \nspectrometry (LC-MS/MS). Improvements \nover the past decade in sample preparation, \nmass spectrometers and the associated \ncomputational proteomics tools have led to \nan exponential increase in the amount of \nphosphoproteomics data. PhosphoSitePlus,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 77
encoding: FLOAT32
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{"title": "Deciphering the human phosphoproteome", "chroma:document": "the largest database of post-translational \nmodifications5, contains >200,000  \nannotated phosphosites. But, for more \nthan 95% of these, the biological function \nor upstream kinase are unknown2. The \nproteomics field still lacks tools to identify \nfunctional phosphosites in an unbiased, \nlarge-scale manner.\nCurrent methods for bioinformatics \nanalysis of phosphoproteomics datasets \ntypically focus on the most highly regulated \nphosphosites using gene ontology, protein \nnetwork and pathway analysis tools. Yet \nmost of these tools treat phosphosite \nregulation as changes in protein expression, \nand they collapse information from multiple \nphosphosites in a protein. By contrast, \nactivated kinases are usually identified \nthrough bulk analysis of phosphosites using \nkinase\u2013substrate enrichment methods. \nThese tools often rely on known kinase\u2013\nsubstrate relationships and/or enrichment \nof predicted kinase recognition motifs6. \nThis information is often integrated with a \nfunctional kinase network6 and/or with the \nphosphosites identified in the kinase itself7.\nThese strategies have been used \nsuccessfully to extract important biological \ninformation from phosphoproteomics \ndatasets, but they often neglect the unique \ninformation encoded in individual \nphosphosites, which can provide deeper \ninsight into biological phenotypes8. \nHowever, systematic analysis of individual \nphosphosites is currently not feasible. \nInstead, phosphosites on relevant proteins \nin a signaling pathway of interest are often \nselected manually for functional validation \nand follow up.\nP-site functional score\n1\n0.5\n0\nFOXO3-S253\nMYC-S62\nMAPK1-T185\nKMT2A-S1850\nNCOR2-SS2245\nSRRM2-S2142\nMaxQuant\nFDR 1%\nPRIDE database\n~ 7,000 experiments\n119,809\nhuman phosphosites\nCCD86-S255\nCFL1-Y89\nATG4B-Y8\nm/z\nV A L S P K\nb1 b2\nb3\nb4\nb5\ny5\ny4\ny3\ny2\ny1\nA1\nA3 A2\nA4\nB1 B2 B3 B4\nC1 C2 C3\nD1\nD3 D2\nD4\nE2 E3 E1\nE4\nF1 F2 F3 F4\nC4\nPhosphoproteomics analysis\nUnraveling phosphorylation\nfunctionality\nP\nP\nP\nP\nMS evidence\nStructure\nConservation\nRegulation"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 78
encoding: FLOAT32
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{"title": "Deciphering the human phosphoproteome", "chroma:document": "Fig. 1 | Reanalysis of phosphoproteomics datasets in the PRIDE database provides functional scores for individual phosphosites. To rank phosphosites by \ntheir functional importance, Ochoa et\u00a0al.3 used a machine-learning approach that integrates information about the phosphosites\u2019 regulation, structure and \nconservation, as well as MS-based evidence. The resulting functional score ranks the sites according to their biological significance, which can be used to \nprioritize candidates for subsequent detailed investigation.\nNatuRE BIotEchNology | www.nature.com/naturebiotechnology"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 79
encoding: FLOAT32
metadata:
{"title": "Decoding Sex-Biased Gene Expression Patterns in Heart Disease", "chroma:document": "Decoding Sex-Biased Gene Expression\nPatterns in Heart Disease\nS\nex, a biological determinant of a person\u2019s\nanatomy and physiology, has vital impli-\ncations on disease incidence and preva-\nlence,\nand\nultimately\nclinical\noutcome.1\nRecognized across reproductive and nonrepro-\nductive organs, distinct phenotypes differen-\ntiate women from men not only during the\nreproductive years but also throughout all of\nlife. Sexually dimorphic expression of sex-\nlinked genes, however, does not account for\nall sex differences.2 Rather, the complexity of\nsex differences in health and disease goes\nbeyond\na sex chromosomeedirected\nand\nhormone-centric axis. Indeed, most autosomal\ngenes with sex-biased expression lack androgen\nor estrogen response elements.3 In this context,\nsex-biased gene expression could engender\n(patho)phenotypic sex differences whereby\nautosomal genes, operating identically in males\nand females to in\ufb02uence a trait, are expressed\nmore or less abundantly in one vs the other sex.\nAn integrative foundation on which to ascertain\nsex differences is emerging through large-scale\ndata sets, typically sourced from healthy tis-\nsues and organs containing multiple cell types.\nAlthough a systems-level genetic architecture is\nthereby increasingly delineated, less is known\nregarding the recondite sex-segregated differ-\nentiators of disease vulnerability.\nThis issue of Mayo Clinic Proceedings\nfeatures a cell-speci\ufb01c deciphering of gene\nexpression patterns underpinning sex-biased\ndysregulation in cardiomyopathy.4 Using\npatient-derived cardiomyocytes, Gaignebet\net al4 report linkage of an in\ufb02ammation-\nrelated gene signature with poor organ\nfunction in males but not in females. In this\nway, this innovative work ushers in an era of\nsex-related pathophysiology decoded at a\ncell-autonomous, molecular level.\nSex in Cardiology\nHalf of the adult population in the United\nStatesd51.2% of men and 44.7% of womend\nlives with a cardiovascular condition, under-\nscoring the effect on public health.5 Notably,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 80
encoding: FLOAT32
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{"title": "Decoding Sex-Biased Gene Expression Patterns in Heart Disease", "chroma:document": "males and females demonstrate distinct sus-\nceptibilities for cardiovascular disorders. For\nexample, premenopausal women, compared\nwith age-matched men, are at reduced risk\nfor coronary heart disease, whereas post-\nmenopausal status is linked with aggravated\ncardiovascularmorbidityandmortality.6Aslife\nexpectancy in men and women is continuously\nincreasingly, with that of women to exceed 90\nyears of age in this decade, there is an increased\nemphasis on safeguarding the vulnerable heart.\nDecoding diverse disease trajectories and car-\ndioprotective patterns naturally occurring in a\nsex-biased or age-dependent manner would\ninform a path toward more personalized care.\nSex-Biased Gene Pro\ufb01ling\nA contributor to poor prognosis in heart dis-\nease is maladaptive myocardial remodeling,\nknown to adopt sex-distinctive features.\nMales are particularly susceptible and prone\nto cardiomegaly in the setting of hemody-\nnamic stress. A case in point is advanced left\nventricular\nhypertrophy\ndeveloping\nin\nresponse to pressure overload imposed by\naortic stenosis,7 a clinical condition studied\nby Gaignebet et al.4 Of note, degenerative\naortic stenosis in the elderly is the major eti-\nology of nonrheumatic valvular heart disease\nthat accounts for 25,000 deaths annually in\nthis country. Despite a similar extent of\nout\ufb02ow obstruction in patients undergoing\naortic valve replacement, the left ventricle in\nmales demonstrated structural and functional\nmaladaptation, characterized by an exagger-\nated increase in chamber size, wall thickness,\nand mass index and an aggravated decline in\ncontractility. In a sex-biased genomic pro\ufb01le,\n2 discrete in\ufb02ammatory genes, CCN2 and\nNFKB1, were recognized by high expression\nin cardiomyocytes obtained from male pa-\ntients and remarkably correlated negatively\nSee also page 688\nEDITORIAL\n636\nMayo Clin Proc. n April 2020;95(4):636-638 n https://doi.org/10.1016/j.mayocp.2020.02.013\nwww.mayoclinicproceedings.org n \u00aa 2020 Mayo Foundation for Medical Education and Research"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 81
encoding: FLOAT32
metadata:
{"title": "Organ Weights in Relation to Age and Sex in Cynomolgus Monkeys \\(Macaca fascicularis\\", "chroma:document": "Organ Weights in Relation to Age and Sex in Cynomolgus \nMonkeys (Macaca fascicularis)\nRachel Amato1, Jean F. Gardin2, Janet A. Tooze2, J. Mark Cline2\n1University of Georgia, Athens, Georgia, USA\n2Wake Forest School of Medicine, Winston-Salem, North Carolina, USA\nAbstract\nLaboratory animal research is an important contributor to both human and animal medicine. \nCurrently, there is extensive use of cynomolgus monkeys (Macaca fascicularis) in pathology and \ntoxicology research. The purpose of this study was to define reference values for absolute and \npercentage organ weights in M fascicularis of different ages and sex. Organ weights were obtained \nfrom necropsies of 1022 cynomolgus monkeys at the Wake Forest School of Medicine from 1997 \nto 2018. Distributions of absolute and percentage weights for each organ were described; sex and \nage groups were compared using analysis of variance. Age effects on percentage of body weights \nfor each organ were analyzed within each sex. Diet effects were also analyzed. This evaluation \nshowed that male body weights and absolute organ weights were greater for all age groups; \nhowever, female organ to body weight percentages were greater for most organs. Percentage of \norgan weight to body weight declined for the adrenals, brain, lung, thyroid and thymus during \nmaturation, whereas percentage weight of pancreas, prostate, testes, and uterus increased. Animals \nconsuming a high-fat, Western-type diet had a lower body weight than animals consuming a \ncarbohydrate-rich chow diet. This information will be useful for further toxicology and pathology \nstudies concerning cynomolgus monkeys.\nKeywords\norgan weights; nonhuman primate; cynomolgus; pathology; sex differences; development\nIntroduction\nDue to the genetic and physiologic similarity among primates, nonhuman primates are \noften used in a laboratory research setting as models.1 Currently, there is extensive use \nof cynomolgus monkeys (Macaca fascicularis) in research.2,3 So far, these monkeys have"}


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id: 82
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{"title": "Organ Weights in Relation to Age and Sex in Cynomolgus Monkeys \\(Macaca fascicularis\\", "chroma:document": "Corresponding Author: J. Mark Cline, Department of Pathology, Section on Comparative Medicine, Wake Forest School of \nMedicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. jmcline@wakehealth.edu.\nAuthor Contributions\nAuthors contributed to conception or design (RA, JG, JC); data acquisition, analysis, or interpretation (RA, JG, JT, JC); drafting \nthe manuscript (RA, JG, JC); and critically revising the manuscript (RA, JG, JT, JC). All authors gave final approval and agreed to \nbe accountable for all aspects of work in ensuring that questions relating to the accuracy or integrity of any part of the work are \nappropriately investigated and resolved.\nDeclaration of Conflicting Interests\nThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\nHHS Public Access\nAuthor manuscript\nToxicol Pathol. Author manuscript; available in PMC 2022 July 24.\nPublished in final edited form as:\nToxicol Pathol. 2022 July ; 50(5): 574\u2013590. doi:10.1177/01926233221088283.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 83
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{"title": "Behavioral context affects social signal representations within single primate prefrontal cortex neurons", "chroma:document": "Behavioral context affects social signal representations within \nsingle primate prefrontal cortex neurons\nVladimir Jovanovic1,2, Adam Ryan Fishbein1, Lisa de la Mothe3, Kuo-Fen Lee4, Cory \nThomas Miller1,2,*\n1Cortical Systems and Behavior Laboratory, University of California, San Diego, La Jolla, CA \n92093, USA\n2Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA\n3Department of Psychology, Tennessee State University, Nashville, TN 37209, USA\n4Laboratory for Peptide Biology, Salk Institute, La Jolla, CA 92093, USA\nSummary.\nWe tested whether social signal processing in more traditional, head-restrained contexts is \nrepresentative of the putative natural analog \u2013 social communication \u2013 by comparing responses \nto vocalizations within individual neurons in marmoset prefrontal cortex (PFC) across a series \nof behavioral contexts ranging from traditional to naturalistic. Although vocalization responsive \nneurons were evident in all contexts, cross-context consistency was notably limited. A response to \nthese social signals when subjects were head-restrained was not predictive of a comparable neural \nresponse to the identical vocalizations during natural communication. This pattern was evident \nboth within individual neurons and at a population level, as PFC activity could be reliably decoded \nfor the behavioral context in which vocalizations were heard. These results suggests that neural \nrepresentations of social signals in primate PFC are not static, but highly flexible and likely reflect \nhow nuances of the dynamic behavioral contexts affect the perception of these signals and what \nthey communicate.\neTOC.\n*Lead Contact: corymiller@ucsd.edu.\nAuthor Contributions\nVJ designed the experiment, conducted the experiment, analyzed the data and wrote the paper\nARF analyzed the neurophysiology data and wrote the paper\nLDM analyzed the anatomy data\nKFL analyzed the anatomy data\nCTM designed the experiment, supervised the experiment and wrote the paper\nInclusion and Diversity"}


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{"title": "Behavioral context affects social signal representations within single primate prefrontal cortex neurons", "chroma:document": "One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community.\nDeclaration of Interests\nThe authors declare no competing interests\nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our \ncustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review \nof the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered \nwhich could affect the content, and all legal disclaimers that apply to the journal pertain.\nHHS Public Access\nAuthor manuscript\nNeuron. Author manuscript; available in PMC 2023 April 20.\nPublished in final edited form as:\nNeuron. 2022 April 20; 110(8): 1318\u20131326.e4. doi:10.1016/j.neuron.2022.01.020.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 85
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{"title": "Eur J Clin Investigation - 2022 - Yerly", "chroma:document": "Eur J Clin Invest. 2023;53:e13885. \n \n  | 1 of 13\nhttps://doi.org/10.1111/eci.13885\nwileyonlinelibrary.com/journal/eci\nReceived: 1 July 2022 | Accepted: 4 October 2022\nDOI: 10.1111/eci.13885  \nN A R R AT I V E  R E V I E W\nSex- specific and hormone- related differences in vascular \nremodelling in atherosclerosis\nAna\u00efs\u00a0Yerly1,2,3 |   Emiel P. C.\u00a0van der Vorst4,5,6\n |   Iris\u00a0Baumgartner1,2 |   \nSarah\u00a0Maike\u00a0Bernhard1,2 |   Marc\u00a0Schindewolf1,2 |   Yvonne\u00a0D\u00f6ring1,2,4,5\n1Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland\n2Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland\n3Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland\n4Institute for Cardiovascular Prevention (IPEK), Ludwig- Maximilians- University Munich (LMU), Munich, Germany\n5DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany\n6Institute for Molecular Cardiovascular Research (IMCAR) and Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, \nAachen, Germany\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided \nthe original work is properly cited.\n\u00a9 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation \nJournal Foundation.\nCorrespondence\nYvonne D\u00f6ring, Division of Angiology, \nSwiss Cardiovascular Center, \nInselspital, Bern University Hospital, \nUniversity of Bern, Bern, Switzerland.\nEmail: yvonne.doering@insel.ch\nFunding information\nAard- en Levenswetenschappen, \nNederlandse Organisatie voor \nWetenschappelijk Onderzoek, \nGrant/Award Number: 91619053; \nSchweizerischer Nationalfonds zur \nF\u00f6rderung der Wissenschaftlichen \nForschung, Grant/Award Number: \n310030_197655, 4078P0_198297 and \nCRSII5_193694\nAbstract"}


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{"title": "Eur J Clin Investigation - 2022 - Yerly", "chroma:document": "Abstract\nAtherosclerosis, a lipid- driven inflammatory disease, is the main underlying \ncause of cardiovascular diseases (CVDs) both in men and women. Sex- related \ndimorphisms regarding CVDs and atherosclerosis were observed since more than \na decade ago. Inflammatory mediators such as cytokines, but also endothelial \ndysfunction, vascular smooth muscle cell migration and proliferation lead to vas-\ncular remodelling but are differentially affected by sex. Each year a greater num-\nber of men die of CVDs compared with women and are also affected by CVDs \nat an earlier age (40\u2013 70 years old) while women develop atherosclerosis- related \ncomplications mainly after menopause (60+ years). The exact biological reasons \nbehind this discrepancy are still not well- understood. From the numerous animal \nstudies on atherosclerosis, only a few include both sexes and even less investigate \nand highlight the sex- specific differences that may arise. Endogenous sex hor-\nmones such as testosterone and oestrogen modulate the atherosclerotic plaque \ncomposition and the frequency of such plaques. In men, testosterone seems to \nact like a double- edged sword as its decrease with ageing correlates with an in-\ncreased risk of atherosclerotic CVDs, while testosterone is also reported to pro-\nmote inflammatory immune cell recruitment into the atherosclerotic plaque. In \npremenopausal women, oestrogen exerts anti- atherosclerotic effects, which de-\ncline together with its level after menopause resulting in increased CVD risk in \nageing women. However, the interplay of sex hormones, sex- specific immune re-\nsponses and other sex- related factors is still incompletely understood. This review"}


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id: 87
encoding: FLOAT32
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{"title": "Dopaminergic modulation of striatal function and Parkinson\\220s disease", "chroma:document": "Dopaminergic modulation of striatal function and Parkinson\u2019s \ndisease\nShenyu Zhai1, Weixing Shen1, Steven M Graves2, and D James Surmeier1\n1Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL \n60611, USA\n2Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, \nUSA\nAbstract\nThe striatum is richly innervated by mesencephalic dopaminergic neurons that modulate a diverse \narray of cellular and synaptic functions that control goal-directed actions and habits. The loss of \nthis innervation has long been thought to be the principal cause of the cardinal motor symptoms of \nParkinson\u2019s disease (PD). Moreover, chronic, pharmacological overstimulation of striatal \ndopamine (DA) receptors is generally viewed as the trigger for levodopa-induced dyskinesia (LID) \nin late-stage PD patients. Here, we discuss recent advances in our understanding of the \nrelationship between the striatum and DA, particularly as it relates to PD and LID. First, it has \nbecome clear that chronic perturbations of DA levels in PD and LID bring about cell type-specific, \nhomeostatic changes in spiny projection neurons (SPNs) that tend to normalize striatal activity. \nSecond, perturbations in DA signaling also bring about non-homeostatic aberrations in synaptic \nplasticity that contribute to disease symptoms. Third, it has become evident that striatal \ninterneurons are major determinants of network activity and behavior in PD and LID. Finally, \nrecent work examining the activity of SPNs in freely moving animals has revealed that the \npathophysiology induced by altered DA signaling is not limited to imbalance in the average \nspiking in direct and indirect pathways, but involves more nuanced disruptions of neuronal \nensemble activity.\nKeywords\nParkinson\u2019s disease; levodopa-induced dyskinesia; striatum; dopamine; synaptic plasticity; \ninterneurons\nIntroduction\nThe cardinal motor symptoms of Parkinson\u2019s disease (PD) are caused by progressive"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
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{"title": "Dopaminergic modulation of striatal function and Parkinson\\220s disease", "chroma:document": "degeneration of dopaminergic neurons in the substantia nigra (SN) (Surmeier et al. 2014). In \nthe early stages of the disease, these symptoms of PD are effectively alleviated by dopamine \nCorresponding author: D James Surmeier (j-surmeier@northwestern.edu). \nConflict of interest\nThe authors declare that they have no conflict of interest.\nHHS Public Access\nAuthor manuscript\nJ Neural Transm (Vienna). Author manuscript; available in PMC 2020 April 01.\nPublished in final edited form as:\nJ Neural Transm (Vienna). 2019 April ; 126(4): 411\u2013422. doi:10.1007/s00702-019-01997-y.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 89
encoding: FLOAT32
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{"title": "Episodic Recognition Memory and the Hippocampus in Parkinson\\220s disease: A Review", "chroma:document": "Episodic Recognition Memory and the Hippocampus in \nParkinson\u2019s disease: A Review\nTanusree Das, PhDa, Jaclyn Joyce Hwanga,c, and Kathleen L Poston, MD, MSa,b\naDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, \nStanford, CA, USA. tanusree@stanford.edu\nbDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.\ncDepartment of Neuroscience, University of Pittsburgh. jjh107@pitt.edu\nAbstract\nParkinson\u2019s disease is a progressive neurodegenerative disorder of aging. The hallmark \npathophysiology includes the development of neuronal Lewy bodies in the substantia nigra of the \nmidbrain with subsequent loss of dopaminergic neurons. These neuronal losses lead to the \ncharacteristic motor symptoms of bradykinesia, rigidity, and rest tremor. In addition to these \ncardinal motor symptoms patients with PD experience a wide range of non-motor symptoms, the \nmost important being cognitive impairments that in many circumstances lead to dementia. People \nwith PD experience a wide range of cognitive impairments; in this review we will focus on \nmemory impairment in PD and specifically episodic memory, which are memories of day-to-day \nevents of life. Importantly, these memory impairments severely impact the lives of patients and \ncaregivers alike.\nTraditionally episodic memory is considered to be markedly dependent on the hippocampus; \ntherefore, it is important to understand the exact nature of PD episodic memory deficits in relation \nto hippocampal function and dysfunction. In this review, we discuss an aspect of episodic memory \ncalled recognition memory and its subcomponents called recollection and familiarity. Recognition \nmemory is believed to be impaired in PD; thus, we discuss what aspects of the hippocampus are \nexpected to be deficient in function as they relate to these recognition memory impairments. In \naddition to the hippocampus as a whole, we will discuss the role of hippocampal subfields in \nrecognition memory impairments.\nKeywords"}


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id: 90
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{"title": "Episodic Recognition Memory and the Hippocampus in Parkinson\\220s disease: A Review", "chroma:document": "Keywords\nEpisodic memory; Recognition memory; Hippocampus; Parkinson\u2019s disease; Hippocampal \nsubfields\nCorresponding author Kathleen L. Poston, MD, MS, Department of Neurology and Neurological Sciences, Stanford University \nSchool of Medicine, 780 Welch Road, CJ Huang Building, Palo Alto, CA, USA 94304, klposton@stanford.edu. \nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our \ncustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of \nthe resulting proof before it is published in its final citable form. Please note that during the production process errors may be \ndiscovered which could affect the content, and all legal disclaimers that apply to the journal pertain.\nHHS Public Access\nAuthor manuscript\nCortex. Author manuscript; available in PMC 2020 April 01.\nPublished in final edited form as:\nCortex. 2019 April ; 113: 191\u2013209. doi:10.1016/j.cortex.2018.11.021.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 91
encoding: FLOAT32
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{"title": "Effects of biological sex on the pathophysiology of the heart", "chroma:document": "Themed Section: Biological Sex and Cardiovascular Pharmacology\nREVIEW\nEffects of biological sex on\nthe pathophysiology of\nthe heart\nLoubina Fazal1,2, Feriel Azibani1, Nicolas Vodovar1,\nAlain Cohen Solal1,2,3, Claude Delcayre1 and Jane-Lise Samuel1,2,3\n1UMR-S 942, Inserm, Paris, France, 2University Paris-Diderot, Paris, France, and 3AP-HP H\u00f4pital\nLariboisi\u00e8re, Paris, France\nCorrespondence\nJane-Lise Samuel, UMR-S 942\nInserm, 41 bd de la Chapelle,\n75475 Paris Cedex 10,\nFrance. E-mail:\njane-lise.samuel@inserm.fr\n----------------------------------------------------------------\nKeywords\nheart; gender; hypertrophy;\ncardiac failure\n----------------------------------------------------------------\nReceived\n18 March 2013\nRevised\n15 May 2013\nAccepted\n2 June 2013\nCardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of\nbiological sex on cardiovascular pathophysiology have long been known, the sex-speci\ufb01c mechanisms mediating these\nprocesses have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac\nstructure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the\nresponse of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that\nshould be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches.\nLINKED ARTICLES\nThis article is part of a themed section on Biological Sex and Cardiovascular Pharmacology. To view the other articles in this\nsection visit http://dx.doi.org/10.1111/bph.2014.171.issue-3\nAbbreviations\nAR, androgen receptor; CVD, cardiovascular disease; DOCA, deoxycorticosterone acetate; E-C, excitation-contraction;\nET-1, endothelin-1; ER, oestrogen receptor; HRT, hormone replacement therapy; LV, left ventricular; MI, myocardial\ninfarction; NP, natriuretic peptide; PCH, pathological cardiac hypertrophy; PR, progesterone receptor; RAAS,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 92
encoding: FLOAT32
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{"title": "Effects of biological sex on the pathophysiology of the heart", "chroma:document": "renin-angiotensin-aldosterone system; SERCA, sarco/endoplasmic reticulum Ca2+-ATPase; TAC, thoracic aorta\nconstriction; VSMC, vascular smooth muscle cell\nIntroduction\nCardiovascular diseases (CVDs) are the leading cause of death\nin men and women in industrialized countries. Over the last\ndecade, while little change was noticed on the sex ratio of\ncohorts in the majority of CVD studies (Mosca et al., 2011),\nseveral clinical trials provided evidence that sex is an impor-\ntant determinant of cardiovascular events in patients with\nvascular diseases or high-risk diabetes mellitus. Indeed,\nfemale diabetic patients had a higher risk for acute myocar-\ndial infarction compared to male diabetics (Kappert et al.,\n2012). Women also exhibited a marked increase in the inci-\ndence of left ventricular (LV) hypertrophy after the meno-\npause, when the prevalence of arterial hypertension increases\n(Lopez-Ruiz et al., 2008). Furthermore, women generally\ndisplay better cardiac function and survival in the face of\nCVD than men, although this advantage is lost when com-\nparing\npostmenopausal\nwomen\nwith\nage-matched\nmen\n(Fujimoto et al., 2013).\nThe effects of biological sex on cardiovascular physiol-\nogy or pathology have long been known, but the biological\nmechanisms responsible for sex-related differences started to\nbe unravelled over the last decades. Indeed, sex steroid hor-\nmones (oestrogens in female, testosterone in male) contrib-\nute signi\ufb01cantly to the sex-based differences in the outcome\nof cardiac diseases, although the contribution of environ-\nmental oestrogen-like molecules, such as phytoestrogens,\nmust not be neglected. Thus, hormonal therapy such as\nthe hormone replacement therapy (HRT) after menopause\nusing synthetic oestrogens and progesterone, while broadly\ndebated, may help to understand the effects of oestrogen in\ncardiac pathophysiology. In addition, some elucidation of\nthe interrelation between the sex steroid hormones and\npeptides and/or hormones directly involved in the cardiac"}


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id: 93
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{"title": "Effects of biological sex on the pathophysiology of the heart", "chroma:document": "physiopathology such as the components of the renin\nangiotensin-aldosterone system, and the natriuretic peptides\n(NPs) will be provided. At least, as adequate exercise and\nnutrition programmes were shown to improve the preven-\ntion and the treatment of CVD and metabolic disorders\n(Hagey and Warren, 2008), these lifestyle patterns are begin-\nning to be taken into account in the treatment of post-\nmenopausal women. The collection of such data will be of\ninterest to analyse the relation between exercise, sex and\nCVD.\nBJP\nBritish Journal of\nPharmacology\nDOI:10.1111/bph.12279\nwww.brjpharmacol.org\nBritish Journal of Pharmacology (2014) 171 555\u2013566\n555\n\u00a9 2013 The British Pharmacological Society"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 94
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{"title": "Elevated serotonin and reduced dopamine in subregionally divided Huntington's disease striatum", "chroma:document": "Elevated Serotonin and \nReduced Dopamine in \nSubregionall; Divided \nHunti&ton\u2019s Disease \nStriatum \nStephen J. Kish, PhD,+ Kathleen Shannak, BSc,\u201d \nand Oleh Hornykiewicz, MD*t \nWe measured the rostrocaudal distribution of serotonin, \ndopamine, and their metabolites in Huntington\u2019s disease \nstriatum (caudate and putamen). Mean levels of sero- \ntonin or 5-hydroxyindoleacetic acid were elevated in \nmost striatal subdivisions, whereas concentrations of \ndopamine or its metabolite homovanillic acid were \nslightly to markedly reduced. Dopamine and serotonin \nwere at control levels in the nucleus accumbens and \nsubstantia nigra. Whereas the above-normal serotonin \ncan most likely be accounted for by striatal atrophy, the \nreduced dopamine suggests either a marked down- \nregulation of nigrostriatal dopamine neurons or an \nactual reduction in the arborization of the striatal \ndopamine neurons. As experimental animal data sug- \ngest, the relative excess of striatal serotonin or one of its \nmetabolites may facilitate the neurodegenerative pro- \ncess in Huntington\u2019s disease striatum. \nKish SJ, Shannak K, Hornykiewicz 0: Elevated \nserotonin and reduced dopamine in subregionally \ndivided Huntington\u2019s disease striaturn. \nAnn Neurol 22:386-389, 1987 \nBiochemical analyses of postmortem brain of Hunting- \nton\u2019s disease (HD) patients have consistently shown a \nmarked decrease of neurochemical markers of the in- \ntrinsic striatal neurons containing gamma-aminobutyric \nacid (GABA) [19, 241, acetylcholine [6, 15, 241, sub- \nstance P [S, 10, 131, and increased somatostatin 12, \n181. This is in accord with the well-established neuro- \npathology of HD, which has identified a massive, but \nselective, loss of the intrinsic neuronal cell populations \nin the caudate nucleus and putamen. In contrast, litera- \nture on the neurochemistry in HD brain of the affer- \nent neuronal systems innervating striatal nuclei, espe- \ncially the dopamine and serotonin systems, remains \ncontradictory and sparse. Thus, the striatal level of"}


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{"title": "Elevated serotonin and reduced dopamine in subregionally divided Huntington's disease striatum", "chroma:document": "From the \u2018Human Brain Laboratory, Clarke Institute of Psychiatry, \nToronto, the Departments of Psychiatry and Pharmacology, Univer- \nsity of Toronto, Toronto, Ontario, Canada, and the tInstitute of \nBiochemical Pharmacology, University of Vienna, Vienna, Austria. \nReceived Dec 9, 1986, and in revised form Mar 4, 1987. Accepted \nMar 7, 1987. \nAddress correspondence to Dr Kish, Human Brain Laboratory, \nClarke Institute of Psychiatry, Toronto, Ontario, Canada, M5T lR8. \nchemical markers of dopamine neurons has been vari- \nously reported as normal, reduced, or elevated [ S ,  6, \n15, 16, 20, 241, and the level of serotonin has been \nfound to be somewhat elevated in the caudate nucleus \nand putamen (5-hydroxyindoleacetic acid I5-HIAA) \nnot examined) {51. Knowledge of the precise behavior \nof striatal dopamine and serotonin in the brain of HD \npatients is relevant, particularly because dopamine an- \ntagonists are the only clinical measure for controlling, \neven in part, the involuntary abnormal movements, \nand reduction of striatal serotonin recently has been \nfound to partially protect the striatum from the neuro- \ntoxic effect of kainic acid in a rat model of HD 141. \nIn view of the marked regional variation within HD \nstriatum and of the severity of neurodegenerative \nchange 125) as well as the neurochemical and func- \ntional heterogeneity of mammalian striatal nuclei (see \nIll), we performed a detailed subregional distribution \nstudy of both dopamine and serotonin, and their \nmetabolites homovanillic acid (HVA) and 5-HIAA, in \nfour regions of the HD basal ganglia: the caudate nu- \ncleus, the putamen, the nucleus accumbens, and the \nsubstantia nigra. \nPatients and Methods \nBrains were obtained at autopsy from 7 patients (5 males, 2 \nfemales) who died with the clinical diagnosis of HD (mean \nage k standard error of the mean [SEMI: 58 ? 4 years) and \n11 patients (8 males, 3 females) who died without any evi- \ndence of neurological or psychiatric disorder (control sub-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 96
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{"title": "Elevated serotonin and reduced dopamine in subregionally divided Huntington's disease striatum", "chroma:document": "jects) (mean age: 59 ? 4 years). Drug information could be \nobtained on 5 of the 7 patients with HD. Of these 5 patients, \nall had received long-term administration of neuroleptic \ndrugs for varying periods of time. \nAt autopsy, one half-brain was immersed in formalin fixa- \ntive for neuropathological analysis, whereas the other half- \nbrain was immediately frozen at - 80\u00b0C for biochemical ex- \namination. The mean death-to-freezing intervals for the \npatients with HD (15 ? 3 hours, mean \u2019. SEM) and the \ncontrol subjects (12 ? 2 hours) did not differ significantly \n( p  \nSerotonin, 5-HIAA, dopamine, and HVA were measured \nusing minor modifications of the high-pressure liquid chro- \nmatography-electrochemical method of Felice et a1 [I I]. \n0.05, Student\u2019s two-tailed t test). \nResults \nNeuropathological Findings \nGross and microscopic examination revealed features \ntypical of HD, consisting of severe to moderate cell \nloss and gliosis in the caudate head with less severe cell \nloss in the putamen. Cell loss and gliosis were variable \nin the globus pallidus and minimal in the nucleus ac- \ncumbens. The substantia nigra of the HD cases ap- \npeared normal histologically. \nNeurocbemical Findings \nWhen compared with the corresponding control \nmeans, serotonin levels (Table 1) were generally ele- \n386"}


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id: 97
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{"title": "Gender proteomics I. Which proteins in non-sexual organs", "chroma:document": "Contents lists available at ScienceDirect\nJournal of Proteomics\njournal homepage: www.elsevier.com/locate/jprot\nReview\nGender proteomics I. Which proteins in non-sexual organs\nElisabetta Gianazzaa,\u204e, Ingrid Millerb, Uliano Guerrinia, Luca Palazzoloa, Chiara Parravicinia,\nIvano Eberinia\na Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, I-20133 Milano, Italy\nb Institut f\u00fcr Medizinische Biochemie, Veterin\u00e4rmedizinische Universit\u00e4t Wien, Veterin\u00e4rplatz 1, A-1210 Wien, Austria\nA R T I C L E I N F O\nKeywords:\nSex\nMale\nFemale\nDi\ufb00erential proteins\nPhysiology\nPathology\nA B S T R A C T\nDi\ufb00erences related to gender have long been neglected but recent investigations show that they are widespread\nand may be recognized with all types of omics approaches, both in tissues and in biological \ufb02uids. Our review\ncompiles evidence collected with proteomics techniques in our species, mainly focusing on baseline parameters\nin non-sexual organs in healthy men and women. Data from human specimens had to be replaced with in-\nformation from other mammals every time invasive procedures of sample procurement were involved.\nSigni\ufb01cance: As our knowledge, and the methods to build it, get re\ufb01ned, gender di\ufb00erences need to receive more\nand more attention, as they in\ufb02uence the outcome of all aspects in lifestyle, including diet, exercise and en-\nvironmental factors. In turn this background modulates a di\ufb00erential susceptibility to some disease, or a di\ufb00erent\npathogenetic mechanism, depending on gender, and a di\ufb00erent response to pharmacological therapy. Preparing\nthis review we meant to raise awareness about the gender issue. We anticipate that more and more often, in the\nfuture, separate evaluations will be carried out on male and female subjects as an alternative \u2013 and an upgrade \u2013\nto the current approach of reference and test groups being \u2018matched for age and sex\u2019.\n1. Introduction\nA thorough and systematic assessment of the expression level for the"}


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{"title": "Gender proteomics I. Which proteins in non-sexual organs", "chroma:document": "product(s) of each of the protein-coding genes identi\ufb01ed in the human\ngenome is being carried out through the construction of a Human\nProtein Atlas (http://www.proteinatlas.org) as part of the HUPO en-\ndeavor (https://www.hupo.org). At the level of organ proteomes, the\nAtlas database contrasts testis and prostate to endometrium, ovary and\nplacenta. No data on the contrary are reported about the occurrence of\ndi\ufb00erential regulation of any protein at sites other than gonads and\ngenitals; sex (and age) of tissue donors together with diagnosis are only\nincluded in speci\ufb01c histological and Ref-seq data. No sex-speci\ufb01c in-\nformation is available either from the ProteomicsDB repository, which\ncollects thousands of LC-MS/MS experiments involving human tissues,\ncell lines and body \ufb02uids to provide a draft of the human proteome [1].\nOur review aims at \ufb01lling this gap by compiling evidence on gender-\nspeci\ufb01c di\ufb00erences at the proteomic level throughout organs and tis-\nsues. Such di\ufb00erences have been reported for dioichous plants and for\nmany animals in all phyla. We will focus our report on humans and, to a\nminor extent, on laboratory animals, as their specimens are analyzed\nunder a number of experimental settings as models of physiological and\npathological conditions in our species. As we have long ago seen in our\ninvestigations [2\u20134] and as we summarize in Fig. 1, the di\ufb00erences\nbetween plasma/serum and urine proteomes between males and fe-\nmales in one of these species, Rattus norvegicus, are so obvious that the\norigin of the specimens can be easily guessed from the spot pattern in a\n2-DE slab. Subtler yet signi\ufb01cant di\ufb00erences are observed in human\nbody \ufb02uids and in some human and animal tissues, as we are going to\ndetail in the following.\nOur reference list only contains a little > 100 items. Indeed, on\nmost topics, the reports pointing out gender di\ufb00erences, and proving\nsome features being dependent of sex, amount to a very small fraction\nof the total of proteomics investigations. In some more cases, mostly"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 99
encoding: FLOAT32
metadata:
{"title": "Gender proteomics I. Which proteins in non-sexual organs", "chroma:document": "dealing with the search for biomarkers of disease, the possible occur-\nrence of gender di\ufb00erences was investigated and eventually ruled out:\nseveral features were thus proven independent of sex; to keep our ac-\ncount focused, we do not review these reports but we like to stress that\nrelevance and reliability are equal between evidence in favor or in\ndisfavor of a given conclusion. In most cases, however, the investigated\nfeatures were made operationally independent of sex through com-\nparison/s between/among sex-matched experimental groups; this was\nmost often the case with di\ufb03cult to obtain clinical specimens from\nhuman patients. This amounts to disregard the in\ufb02uence of sex, if any,\nand was routine till recently. Indeed, also the endeavor of gender\nmedicine, as aiming at understanding the di\ufb00erences of patho-phy-\nsiology, clinical signs, prevention and treatment of diseases equally\nhttp://dx.doi.org/10.1016/j.jprot.2017.10.002\nReceived 19 July 2017; Received in revised form 26 September 2017; Accepted 4 October 2017\n\u204e Corresponding author.\nE-mail address: elisabetta.gianazza@unimi.it (E. Gianazza).\nJournal of Proteom\nics xxx (xxxx) xxx\u2013xxx\n1874-3919/ \u00a9\n 2017 Published by Elsevier B.V.\nPlease cite this article as: Gianazza, E., Journal of Proteom\nics (2017), http://dx.doi.org/10.1016/j.jprot.2017.10.002"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 100
encoding: FLOAT32
metadata:
{"title": "Evolutionary and biomedical insights from a marmoset diploid genome assembly", "chroma:document": "Nature | Vol 594 | 10 June 2021 | 227\nArticle\nEvolutionary and biomedical insights from a \nmarmoset diploid genome assembly\nChentao Yang1,2,19, Yang Zhou1,19, Stephanie Marcus3,19, Giulio Formenti3,4, Lucie A. Bergeron2, \nZhenzhen Song5, Xupeng Bi1, Juraj Bergman6, Marjolaine Marie C. Rousselle6, \nChengran Zhou1, Long Zhou1, Yuan Deng1,2, Miaoquan Fang1, Duo Xie1, Yuanzhen Zhu1, \nShangjin Tan1, Jacquelyn Mountcastle4, Bettina Haase4, Jennifer Balacco4, Jonathan Wood7, \nWilliam Chow7, Arang Rhie8, Martin Pippel9,10, Margaret M. Fabiszak11, Sergey Koren8, \nOlivier Fedrigo4, Winrich A. Freiwald11,12, Kerstin Howe7, Huanming Yang1,5,13,14, \nAdam M. Phillippy8, Mikkel Heide Schierup6, Erich D. Jarvis3,4,15 & Guojie Zhang2,16,17,18\u2009\u2709\nThe accurate and complete assembly of both haplotype sequences of a diploid \norganism is essential to understanding the role of variation in genome functions, \nphenotypes and diseases1. Here, using a trio-binning approach, we present a \nhigh-quality, diploid reference genome, with both haplotypes assembled \nindependently at the chromosome level, for the common marmoset (Callithrix \njacchus), an primate model system that is widely used in biomedical research2,3. The \nfull spectrum of heterozygosity between the two haplotypes involves 1.36% of the \ngenome\u2014much higher than the 0.13% indicated by the standard estimation based on \nsingle-nucleotide heterozygosity alone. The de\u00a0novo mutation rate is 0.43\u00a0\u00d7\u00a010\u22128 per \nsite per generation, and the paternal inherited genome acquired twice as many \nmutations as the maternal. Our diploid assembly enabled us to discover a recent \nexpansion of the sex-differentiation region and unique evolutionary changes in the \nmarmoset Y\u00a0chromosome. In addition, we identified many genes with signatures of \npositive selection that might have contributed to the evolution of Callithrix biological \nfeatures. Brain-related genes were highly conserved between marmosets and \nhumans, although several genes experienced lineage-specific copy number variations"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 101
encoding: FLOAT32
metadata:
{"title": "Evolutionary and biomedical insights from a marmoset diploid genome assembly", "chroma:document": "or diversifying selection, with implications for the use of marmosets as a model \nsystem.\nA diploid organism carries two haploid genomes with a range of vari-\nants, which make substantial contributions to phenotypic variation4. \nPhased haplotype assemblies can help to reveal the cis- and trans-acting \nvariants on the two homologous genomes. However, most contempo-\nrary de\u00a0novo genome-sequencing efforts produce a single mosaic refer-\nence genome derived from parts of both maternal and paternal alleles, \nwith variations between homologous chromosomes normally being \ndisregarded. As a consequence, these methods usually fail to assemble \ngenomic regions with high heterogeneity, resulting in fragmented \nsequences. A few methods have been developed to produce partial \nhaplotype-phased genome assemblies and showed power in using \nlong sequencing reads to produce long haplotigs (haplotype-specific \ncontigs)5,6. However, producing an assembly that is completely phased \nat the chromosome level for both haplotypes of a diploid genome \nremains a challenge. Here, as part of the Vertebrate Genomes Project, \nwe used a trio-binning approach7,8 to produce a chromosome-level, \nfully haplotype-resolved diploid genome assembly for the common \nmarmoset, C. jacchus. This New World primate has been established \nas an animal model for a broad range of biomedical research such as \nneuroscience, stem cell biology and regenerative medicine2,3. With \nour high-quality diploid assembly, we discovered new properties of \nheterozygosity on both autosomes and sex chromosomes of this pri-\nmate species.\nDiploid genome assembly\nWe generated 63\u00d7-coverage PacBio continuous long reads, 55\u00d7 10X \nGenomics Chromium linked-reads, 154\u00d7 Bionano optical molecules, \nhttps://doi.org/10.1038/s41586-021-03535-x\nReceived: 20 September 2020\nAccepted: 12 April 2021\nPublished online: 28 April 2021\nOpen access\n Check for updates"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 102
encoding: FLOAT32
metadata:
{"title": "Evolutionary and biomedical insights from a marmoset diploid genome assembly", "chroma:document": "1BGI-Shenzhen, Shenzhen, China. 2Villum Centre for Biodiversity Genomics, Section for Ecology and Evolution, Department of Biology, University of Copenhagen, Copenhagen, Denmark. \n3Laboratory of Neurogenetics of Language, The Rockefeller University, New York, NY, USA. 4Vertebrate Genome Laboratory, The Rockefeller University, New York, NY, USA. 5University of the \nChinese Academy of Sciences, Beijing, China. 6Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. 7Wellcome Sanger Institute, Hinxton, UK. 8Genome Informatics Section, \nComputational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. 9Max Planck Institute of Molecular Cell Biology \nand Genetics, Dresden, Germany. 10Center for Systems Biology, Dresden, Germany. 11Laboratory of Neural Systems, The Rockefeller University, New York, NY, USA. 12Center for Brains, Minds and \nMachines (CBMM), The Rockefeller University, New York, NY, USA. 13James D. Watson Institute of Genome Sciences, Hangzhou, China. 14Guangdong Provincial Academician Workstation of BGI \nSynthetic Genomics, BGI-Shenzhen, Shenzhen, China. 15Howard Hughes Medical Institute, Chevy Chase, MD, USA. 16State Key Laboratory of Genetic Resources and Evolution, Kunming \nInstitute of Zoology, Chinese Academy of Sciences, Kunming, China. 17China National GeneBank, BGI-Shenzhen, Shenzhen, China. 18Center for Excellence in Animal Evolution and Genetics, \nChinese Academy of Sciences, Kunming, China. 19These authors contributed equally: Chentao Yang, Yang Zhou, Stephanie Marcus. \u2709e-mail: guojie.zhang@bio.ku.dk"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 103
encoding: FLOAT32
metadata:
{"title": "Expression of Trk isoforms in brain regions and in the striatum of patients with Alzheimer's disease", "chroma:document": "Expression of Trk Isoforms in Brain Regions and in the Striatum\nof Patients with Alzheimer\u2019s Disease\nPierre Dubus, Baptiste Faucheux,* Florence Boissie`re,* Alexis Groppi, Claude Vital,\u2020 Anne Vital,\u2020\nYves Agid,* Etienne C. Hirsch,* and Jean Philippe Merlio\nLaboratoire d\u2019Histologie-Embryologie, EA 2406 Universite\u00b4 de Bordeaux 2, BP 8, 33076 Bordeaux Cedex, France; *INSERM U289, Ho\u02c6pital\nde la Salpe\u02c6trie`re, 75651 Paris Cedex 13, France; and \u2020Service d\u2019Anatomie Pathologique, Ho\u02c6pital Pellegrin, 33076 Bordeaux Cedex, France\nReceived November 30, 1998; accepted March 23, 2000\nThe TrkAII tyrosine kinase receptor differs from the\nTrkAI isoform by an insertion of six amino acids in the\nextracellular domain. We used RT-PCR to determine\ntheir respective distribution in rat and human brain.\nOnly trkAII transcripts were detected in 12 rat brain\nregions, while both trkAI and trkAII transcripts were\ndetected in the cerebellum and pituitary gland. In hu-\nman, both trkAI and trkAII transcripts were detected\nin the frontal, temporal, and occipital cortex and thal-\namus, while only trkAI transcripts were detected in\nthe hippocampus and cerebellum. In the caudate and\nputamen,\ntrkAII\ntranscripts\nwere\nexclusively\nde-\ntected. Thereafter, we studied the expression of TrkA\nisoforms in the striatum of \ufb01ve patients with Alzhei-\nmer\u2019s disease (AD), four patients with non-AD demen-\ntia, seven patients with Parkinson\u2019s disease, and six\npaired nondemented elderly control individuals. In\ncontrols and non-AD patients, a constant expression of\ntrkAII transcripts was detected within all striatum\nparts. In AD patients, a heterogeneous decrease in\ntrkAII expression was observed in the caudate, puta-\nmen, and ventral striatum, resulting either in a drop of\ntrkAII transcript levels or in a weak coampli\ufb01cation of\ntrkAII and trkAI transcripts. The alteration of TrkAII\ngene expression paralleled those of choline acetyl-\ntransferase. Together with previous data, this sug-\ngests that the alteration of trk gene expression could"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 104
encoding: FLOAT32
metadata:
{"title": "Expression of Trk isoforms in brain regions and in the striatum of patients with Alzheimer's disease", "chroma:document": "contribute to a decrease in NGF binding sites and its\nprotective\neffects\non\ncholinergic\nneurons\nof\nAD\npatients.\n\u00a9 2000 Academic Press\nKey Words: Trk; nerve growth factor; neurotrophin;\nstriatum; human brain; PCR; Alzheimer\u2019s disease; Par-\nkinson\u2019s disease.\nINTRODUCTION\nNerve growth factor (NGF) is critical for the devel-\nopment and maintenance of restricted neuronal popu-\nlations in the brain, which include cholinergic neurons\nof the basal forebrain and the striatum (reviewed in\n(46, 56)). These cells express high-af\ufb01nity binding sites\nfor NGF (45, 55) that require the presence of a tyrosine\nkinase receptor Trk or TrkA (26, 28). Binding of NGF\nto TrkA triggers activation of its kinase and autophos-\nphorylation, resulting in a cascade of intracellular\nevents mediating NGF neurotrophic support (reviewed\nin (3)). The accessory presence of the low-af\ufb01nity p75\nneurotrophin receptor (p75NTR) in cells expressing\nboth receptors may modulate TrkA and NGF interac-\ntions (for review see (9)).\nAll NGF-dependent neurons have been shown to ex-\npress trkA transcripts both in the developing and in the\nadult CNS (23, 24, 39). While other neurotrophins such\nas NT-3 or NT-4/5 may activate TrkA with a lower\nef\ufb01ciency than NGF (5, 15), NGF does not bind to other\nmembers of the Trk family such as TrkB or TrkC (25).\nSeveral truncated receptors lacking the kinase do-\nmain have been identi\ufb01ed for TrkB and TrkC but not\nfor TrkA (reviewed in (3)). The trkA protooncogene\nencodes two tyrosine protein kinase isoforms differing\nin a six-amino-acid residue present in the extracellular\nregion of the TrkAII isoform (4, 37, 38). Their expres-\nsion is the result of alternative splicing of a miniexon in\nthe pre-mRNA, and both receptors include the NGF-\nbinding site in their ectodomain (4). Functional studies\nhave suggested that the two isoforms have similar\nbiological properties in both \ufb01broblast cell lines and\nCOS cells expressing ectopic TrkA (4, 28, 38). However,\nin PC12-transfected cell lines, both isoforms are com-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 105
encoding: FLOAT32
metadata:
{"title": "Expression of Trk isoforms in brain regions and in the striatum of patients with Alzheimer's disease", "chroma:document": "parably activated by NGF, but the TrkAII isoform\nshowed higher activation by NT-3 than the TrkAI iso-\nform (12). In addition, the expression of each variant\nprimarily appeared to be tissue-speci\ufb01c with a predom-\ninant expression of trkAII transcripts over trkAI tran-\nscripts in neuronal cells and a unique expression of\ntrkAI in cells of nonneuronal origin (4).\nThe short nucleotide sequence speci\ufb01c to trkAII tran-\nscripts does not allow the anatomical distribution of\neach isoform to be investigated by in situ hybridization\n(ISH). Therefore, we decided to examine the expression\nof TrkA isoforms in rat and human brain regions by\nmeans of RT-PCR. Differences between rat and human\nExperimental Neurology 165, 285\u2013294 (2000)\ndoi:10.1006/exnr.2000.7447, available online at http://www.idealibrary.com on\n285\n0014-4886/00 $35.00\nCopyright \u00a9 2000 by Academic Press\nAll rights of reproduction in any form reserved."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 106
encoding: FLOAT32
metadata:
{"title": "Gender differences in autoimmune disease", "chroma:document": "Review\nGender differences in autoimmune disease\nS.T. Ngo a,b,1, F.J. Steyn a,1, P.A. McCombe b,c,\u21d1\na School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia\nb University of Queensland Centre for Clinical Research, University of Queensland, Herston, Queensland, Australia\nc Department of Neurology, Royal Brisbane & Women\u2019s Hospital, Herston, Queensland, Australia\na r t i c l e\ni n f o\nArticle history:\nAvailable online 2 May 2014\nKeywords:\nAutoimmunity\nGender\nSex differences\nImmune system\na b s t r a c t\nAutoimmune diseases are a range of diseases in which the immune response to self-antigens results in\ndamage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect speci\ufb01c organs\nor body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby\nfemales are generally more frequently affected than males. In this review, we consider gender differences\nin systemic and organ-speci\ufb01c autoimmune diseases, and we summarize human data that outlines the\nprevalence of common autoimmune diseases speci\ufb01c to adult males and females in countries commonly\nsurveyed. We discuss possible mechanisms for sex speci\ufb01c differences including gender differences in\nimmune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones,\ngenetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a\nsigni\ufb01cant in\ufb02uence on the development of autoimmune disease. Thus, considerations of gender should\nbe at the forefront of all studies that attempt to de\ufb01ne mechanisms that underpin autoimmune disease.\n\u0002 2014 Published by Elsevier Inc.\n1. Introduction\nAutoimmune disease, \ufb01rst recognized by Ian Mackay and\nMacfarlane Burnet, is characterized by the failure of an organism\nto tolerate its own cells and tissues, resulting in an aberrant\nimmune response by lymphocytes and/or antibodies (Mackay\nand Burnet, 1963). This leads to pathological changes and dysfunc-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 107
encoding: FLOAT32
metadata:
{"title": "Gender differences in autoimmune disease", "chroma:document": "tion of the tissue that is the target of the self-directed immune\nresponse. Autoimmune diseases can be systemic or can affect\nspeci\ufb01c organs or body systems including the endocrine, gastro-\nintestinal and liver, rheumatological, and neurological systems. In\nthis review, we discuss systemic and organ-speci\ufb01c autoimmune\ndiseases. In general there is a greater prevalence of autoimmune\ndisease in females than males, although there are exceptions. To\ndemonstrate sex differences in autoimmune disease, we summa-\nrize human data to provide an overview of the prevalence in males\nand females of common autoimmune diseases in countries\ncommonly surveyed. We then discuss possible mechanisms for\nsex speci\ufb01c differences.\n1.1. Autoimmunity and autoimmune disease \u2013 key considerations for\nsexual dimorphism\nAutoimmune diseases comprise a range of diseases in which the\nimmune response to self-antigens results in damage or dysfunction\nof tissues (Mackay and Burnet, 1963). Criteria have been developed\nthat allow a disease to be classi\ufb01ed as autoimmune (Rose and\nBona, 1993). These criteria include the identi\ufb01cation of a target\nantigen, the presence of antibodies and/or T cells in the target\norgan, and the transfer of disease to animals by cells or antibodies\n(Rose and Bona, 1993; Witebsky et al., 1957). The immune system\nis comprised of multiple cell types of a single lineage. Collectively,\nthese cells contribute to acquired and innate immunity. Interac-\ntions between acquired and innate immune function may aggra-\nvate autoimmune responses. A strong in\ufb02ammatory component,\nwith in\ufb01ltration of tissue with macrophages and lymphocytes, is\nassociated with many organ-speci\ufb01c autoimmune diseases, such\nas in rheumatoid arthritis (RA) and multiple sclerosis (MS). Non-\nin\ufb02ammatory conditions like myasthenia gravis (MG) are anti-\nbody-mediated, although there may be some minor lymphocyte\nin\ufb01ltration. Systemic lupus erythematosus (SLE) is another impor-\ntant antibody-mediated disease.\nThe origin of autoimmune disease is a disruption of immune"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 108
encoding: FLOAT32
metadata:
{"title": "Gender differences in autoimmune disease", "chroma:document": "tolerance of self-antigens. This is thought to occur in genetically\nsusceptible individuals after exposure to environmental triggers\n(Mackay, 2001). Autoimmune diseases are strongly associated with\nhttp://dx.doi.org/10.1016/j.yfrne.2014.04.004\n0091-3022/\u0002 2014 Published by Elsevier Inc.\n\u21d1 Corresponding author at: University of Queensland Centre for Clinical Research,\nUniversity of Queensland, Herston, Queensland, Australia. Fax: +61 7 38327447.\nE-mail address: pamela.mccombe@uq.edu.au (P.A. McCombe).\n1 Authors contributed equally.\nFrontiers in Neuroendocrinology 35 (2014) 347\u2013369\nContents lists available at ScienceDirect\nFrontiers in Neuroendocrinology\njournal homepage: www.elsevier.com/locate/yfrne\nOpen access under CC BY-NC-ND license.\nOpen access under CC BY-NC-ND license."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 109
encoding: FLOAT32
metadata:
{"title": "Hippocampal neurogenesis: learning to remember", "chroma:document": "Hippocampal neurogenesis: learning to remember\nOrly Lazarov* and Carolyn Hollands\nDepartment of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA\nAbstract\nAlzheimer\u2019s disease, the most prevalent form of dementia in the elderly, is characterized by \nprogressive memory loss and cognitive dysfunction. It has become increasingly clear that while \nneuronal cell loss in the entorhinal cortex and hippocampus occurs in Alzheimer\u2019s disease, it is \npreceded by a long period of deficits in the connectivity of the hippocampal formation that \ncontributes to the vulnerability of these circuits. Hippocampal neurogenesis plays a role in the \nmaintenance and function of the dentate gyrus and hippocampal circuitry. This review will \nexamine the evidence suggesting that hippocampal neurogenesis plays a role in cognitive function \nthat is affected in Alzheimer\u2019s disease, will discuss the cognitive assessments used for the \ndetection of Alzheimer\u2019s disease in humans and rodent models of familial Alzheimer\u2019s disease, \nand their value for unraveling the mechanism underlying the development of cognitive \nimpairments and dementia.\nGraphical Abstract\nAssociate Professor, University of Illinois at Chicago, Department of Anatomy and Cell Biology, 808 South Wood Street, CME 578, \nChicago, IL 60612, USA. Phone: 312-355-0548, fax: 312 413 0354. \nThis is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing \nthis early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it \nis published in its final citable form. Please note that during the production process errors may be discovered which could affect the \ncontent, and all legal disclaimers that apply to the journal pertain.\nConflict of interest\nThe authors declare no conflict of interest on the content of this review.\nHHS Public Access\nAuthor manuscript\nProg Neurobiol. Author manuscript; available in PMC 2017 March 01."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 110
encoding: FLOAT32
metadata:
{"title": "Hippocampal neurogenesis: learning to remember", "chroma:document": "Published in final edited form as:\nProg Neurobiol. 2016 ; 138-140: 1\u201318. doi:10.1016/j.pneurobio.2015.12.006.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 111
encoding: FLOAT32
metadata:
{"title": "Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus", "chroma:document": "Citation: Qiu, H.; Li, H.; Fan, R.;\nSong, Y.; Pan, X.; Zhang, C.; Li, J.\nGenome-Wide DNA Methylation\nPro\ufb01le Indicates Potential Epigenetic\nRegulation of Aging in the Rhesus\nMacaque Thymus. Int. J. Mol. Sci.\n2022, 23, 14984. https://doi.org/\n10.3390/ijms232314984\nAcademic Editor: Zhe Liang\nReceived: 21 October 2022\nAccepted: 24 November 2022\nPublished: 29 November 2022\nPublisher\u2019s Note: MDPI stays neutral\nwith regard to jurisdictional claims in\npublished maps and institutional af\ufb01l-\niations.\nCopyright:\n\u00a9 2022 by the authors.\nLicensee MDPI, Basel, Switzerland.\nThis article is an open access article\ndistributed\nunder\nthe\nterms\nand\nconditions of the Creative Commons\nAttribution (CC BY) license (https://\ncreativecommons.org/licenses/by/\n4.0/).\n \nInternational Journal of \nMolecular Sciences\nArticle\nGenome-Wide DNA Methylation Pro\ufb01le Indicates Potential\nEpigenetic Regulation of Aging in the Rhesus Macaque Thymus\nHong Qiu\n, Haobo Li, Ruiwen Fan, Yang Song, Xuan Pan, Chunhui Zhang and Jing Li *\nKey Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences,\nSichuan University, Chengdu 610064, China\n* Correspondence: lijingsk@scu.edu.cn\nAbstract: We analyzed whole-genome bisul\ufb01te sequencing (WGBS) and RNA sequencing data of two\nyoung (1 year old) and two adult (9 years old) rhesus macaques (Macaca mulatta) to characterize the\ngenomic DNA methylation pro\ufb01le of the thymus and explore the molecular mechanism of age-related\nchanges in the thymus. Combining the two-omics data, we identi\ufb01ed correlations between DNA\nmethylation and gene expression and found that DNA methylation played an essential role in the\nfunctional changes of the aging thymus, especially in immunity and coagulation. The hypomethyla-\ntion levels of C3 and C5AR2 and the hypermethylation level of C7 may lead to the high expressions\nof these genes in adult rhesus macaque thymuses, thus activating the classical complement path-\nway and the alternative pathway and enhancing their innate immune function. Adult thymuses"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 112
encoding: FLOAT32
metadata:
{"title": "Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus", "chroma:document": "had an enhanced coagulation pathway, which may have resulted from the hypomethylation and\nupregulated expressions of seven coagulation-promoting factor genes (F13A1, CLEC4D, CLEC4E,\nFCN3, PDGFRA, FGF2 and FGF7) and the hypomethylation and low expression of CPB2 to inhibit\nthe degradation of blood clots. Furthermore, the functional decline in differentiation, activation and\nmaturation of T cells in adult thymuses was also closely related to the changes in methylation levels\nand gene expression levels of T cell development genes (CD3G, GAD2, ADAMDEC1 and LCK) and\nthe thymogenic hormone gene TMPO. A comparison of the age-related methylated genes among\nfour mammal species revealed that most of the epigenetic clocks were species-speci\ufb01c. Furthermore,\nbased on the genomic landscape of allele-speci\ufb01c DNA methylation, we identi\ufb01ed several age-related\nclustered sequence-dependent allele-speci\ufb01c DNA methylated (cS-ASM) genes. Overall, these DNA\nmethylation patterns may also help to assist with understanding the mechanisms of the aging thymus\nwith the epigenome.\nKeywords: DNA methylation; mRNA expression; thymus; aging; ASM\n1. Introduction\nAs one of the key immunological organs, the thymus is an essential organ for the\ngeneration of the adaptive immune system and involves the differentiation and maturation\nof T lymphocytes (T cells) [1]. The thymus is also an organ of the endocrine system and by\nusing the thymic hormone and thymosin, it regulates immune function [2]. The organ and\nthymic hormone have synergistic or antagonistic actions within several endocrine glands [2].\nIn most mammals, a peculiar feature of the thymus is that it shrinks or disappears as an\nindividual gets older. The thymus starts deteriorating after birth, and thymic cells are\neventually replaced by adipocytes [3,4]. Along with the age-related decrease in size and\nactivity of the thymus comes an associated functional decline [5,6]. However, the molecular\nregulation mechanism of thymus development and aging remains unresolved."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 113
encoding: FLOAT32
metadata:
{"title": "Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus", "chroma:document": "As an important epigenetic modification, DNA methylation plays vital roles in cell\ndifferentiation, tissue-specific gene expression, genomic imprinting and X chromosome\ninactivation in both animals and plants. DNA methylation mainly regulates gene silencing\nInt. J. Mol. Sci. 2022, 23, 14984. https://doi.org/10.3390/ijms232314984\nhttps://www.mdpi.com/journal/ijms"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 114
encoding: FLOAT32
metadata:
{"title": "Human Lung Tissue Transcriptome: Influence of Sex and Age", "chroma:document": "RESEARCH ARTICLE\nHuman Lung Tissue Transcriptome: Influence\nof Sex and Age\nMatteo Dugo1\u2021, Chiara E. Cotroneo2\u00a4\u2021, Emilie Lavoie-Charland3, Matteo Incarbone4,\nLuigi Santambrogio5, Lorenzo Rosso5, Maarten van den Berge6, David Nickle7, Peter\nD. Pare\u00b48,9, Yohan Bosse\u00b43,10, Tommaso A. Dragani2*, Francesca Colombo2\n1 Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei\nTumori, Milan, Italy, 2 Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto\nNazionale dei Tumori, Milan, Italy, 3 Institut Universitaire de cardiologie et de pneumologie de Que\u00b4bec,\nQue\u00b4bec, Canada, 4 Department of Surgery, San Giuseppe Hospital\u2013MultiMedica, Milan, Italy, 5 Fondazione\nIRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy, 6 University of Groningen, University\nMedical Center Groningen, Department of Pulmonology, Groningen Research Institute for Asthma and COPD\n(GRIAC), Groningen, The Netherlands, 7 Merck & Co. Inc., Rahway, NJ, United States of America,\n8 University of British Columbia Center for Heart Lung Innovation and Institute for Heart and Lung Health,\nSt. Paul\u2019s Hospital, Vancouver, BC, Canada, 9 Respiratory Division, Department of Medicine, The University\nof British Columbia, Vancouver, BC, Canada, 10 Department of Molecular Medicine, Laval University,\nQue\u00b4bec, Canada\n\u00a4 Current address: UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield,\nDublin, Ireland.\n\u2021 These authors are co-first authors on this work.\n* tommaso.dragani@istitutotumori.mi.it\nAbstract\nBackground\nSex and age strongly influence the pathophysiology of human lungs, but scarce information\nis available about their effects on pulmonary gene expression.\nMethods\nWe followed a discovery-validation strategy to identify sex- and age-related transcriptional\ndifferences in lung.\nResults\nWe identified transcriptional profiles significantly associated with sex (215 genes; FDR <"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 115
encoding: FLOAT32
metadata:
{"title": "Human Lung Tissue Transcriptome: Influence of Sex and Age", "chroma:document": "0.05) and age at surgery (217 genes) in non-involved lung tissue resected from 284 lung\nadenocarcinoma patients. When these profiles were tested in three independent series of\nnon-tumor lung tissue from an additional 1,111 patients, we validated the association with\nsex and age for 25 and 22 genes, respectively. Among the 17 sex-biased genes mapping on\nchromosome X, 16 have been reported to escape X-chromosome inactivation in other tis-\nsues or cells, suggesting that this mechanism influences lung transcription too. Our 22 age-\nrelated genes partially overlap with genes modulated by age in other tissues, suggesting\nthat the aging process has similar consequences on gene expression in different organs.\nFinally, seven genes whose expression was modulated by sex in non-tumor lung tissue,\nbut no age-related gene, were also validated using publicly available data from 990 lung\nPLOS ONE | DOI:10.1371/journal.pone.0167460\nNovember 30, 2016\n1 / 16\na11111\nOPEN ACCESS\nCitation: Dugo M, Cotroneo CE, Lavoie-Charland E,\nIncarbone M, Santambrogio L, Rosso L, et al.\n(2016) Human Lung Tissue Transcriptome:\nInfluence of Sex and Age. PLoS ONE 11(11):\ne0167460. doi:10.1371/journal.pone.0167460\nEditor: Baochuan Lin, Defense Threat Reduction\nAgency, UNITED STATES\nReceived: September 23, 2015\nAccepted: November 15, 2016\nPublished: November 30, 2016\nCopyright: \u00a9 2016 Dugo et al. This is an open\naccess article distributed under the terms of the\nCreative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited.\nData Availability Statement: Gene expression data\nwere deposited in the Gene Expression Omnibus\ndatabase (GEO, http://www.ncbi.nlm.nih.gov/geo/)\nwith accession number GSE71181.\nFunding: This work was supported by grants from\nthe Italian Association for Cancer Research (AIRC,\ngrant no. 14714). One of the authors (D.N.) has an\naffiliation to a commercial funder of this research\n(Merck & Co. Inc.); the funder provided support in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 116
encoding: FLOAT32
metadata:
{"title": "Human Lung Tissue Transcriptome: Influence of Sex and Age", "chroma:document": "the form of salary for the author (D.N.), but did not\nhave any additional role in the study design, data\ncollection and analysis, decision to publish, or\npreparation of the manuscript. The specific roles of"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 117
encoding: FLOAT32
metadata:
{"title": "The aTSR Domain of Plasmodium Circumsporozoite Protein Bound Heparan Sulfates and Elicited High Titers of Sporozoite Binding Antibody After Displayed by Nanoparticles", "chroma:document": "O R I G I N A L  R E S E A R C H\nThe \u03b1TSR Domain of Plasmodium Circumsporozoite \nProtein Bound Heparan Sulfates and Elicited High \nTiters of Sporozoite Binding Antibody After \nDisplayed by Nanoparticles\nMing Xia1, Frank Vago2, Ling Han\n3, Pengwei Huang1, Linh Nguyen3, Geert-Jan Boons4\u20136, John S Klassen3, \nWen Jiang2, Ming Tan\n1,7\n1Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA; 2Department of Biological Sciences, Purdue \nUniversity, West Lafayette, IN, USA; 3Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; 4Complex Carbohydrate \nResearch Center, University of Georgia, Athens, GA, USA; 5Department of Chemistry, University of Georgia, Athens, GA, USA; 6Department of \nChemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, and Bijvoet Center for Biomolecular Research, Utrecht \nUniversity, Utrecht, the Netherlands; 7Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA\nCorrespondence: Ming Tan, Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, \n45229-3039, USA, Tel +1 513-636-0510, Fax +1 513-636-7655, Email ming.tan@cchmc.org \nIntroduction: Malaria is a devastating infectious illness caused by protozoan Plasmodium parasites. The circumsporozoite protein \n(CSP) on Plasmodium sporozoites binds heparan sulfate proteoglycan (HSPG) receptors for liver invasion, a critical step for \nprophylactic and therapeutic interventions.\nMethods: In this study, we characterized the \u03b1TSR domain that covers region III and the thrombospondin type-I repeat (TSR) of the \nCSP using various biochemical, glycobiological, bioengineering, and immunological approaches.\nResults: We found for the first time that the \u03b1TSR bound heparan sulfate (HS) glycans through support by a fused protein, indicating that \nthe \u03b1TSR is a key functional domain and thus a vaccine target. When the \u03b1TSR was fused to the S domain of norovirus VP1, the fusion"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 118
encoding: FLOAT32
metadata:
{"title": "The aTSR Domain of Plasmodium Circumsporozoite Protein Bound Heparan Sulfates and Elicited High Titers of Sporozoite Binding Antibody After Displayed by Nanoparticles", "chroma:document": "protein self-assembled into uniform S60-\u03b1TSR nanoparticles. Three-dimensional structure reconstruction revealed that each nanoparticle \nconsists of an S60 nanoparticle core and 60 surface displayed \u03b1TSR antigens. The nanoparticle displayed \u03b1TSRs retained the binding \nfunction to HS glycans, indicating that they maintained authentic conformations. Both tagged and tag-free S60-\u03b1TSR nanoparticles were \nproduced via the Escherichia coli system at high yield by scalable approaches. They are highly immunogenic in mice, eliciting high titers \nof \u03b1TSR-specific antibody that bound specifically to the CSPs of Plasmodium falciparum sporozoites at high titer.\nDiscussion and Conclusion: Our data demonstrated that the \u03b1TSR is an important functional domain of the CSP. The S60-\u03b1TSR \nnanoparticle displaying multiple \u03b1TSR antigens is a promising vaccine candidate potentially against attachment and infection of \nPlasmodium parasites.\nKeywords: malaria, Plasmodium, \u03b1TSR domain, receptor binding domain, S60 nanoparticle, malaria vaccine, norovirus\nIntroduction\nMalaria is a deadly, transmissible human disease caused by unicellular protozoan parasites that are members of the \nPlasmodium genus in the family Plasmodiidae. The World Health Organization (WHO) estimated that about 40% of the \nglobal population is at risk of Plasmodium infection and that Plasmodium infection resulted in approximately 241 million \nmalaria cases in 2020, claiming around 627,000 lives worldwide.1 Thus, malaria remains a major threat to global public \nhealth. Various countermeasures have been attempted to prevent malaria, including control of mosquito vectors carrying \nPlasmodium parasites, generations of antimalarial drugs, and development of vaccines.2 However, due to the resistance \nagainst insecticide by mosquitos and the diminished effects of antimalarial medicines owing to the resistance developed \nInternational Journal of Nanomedicine 2023:18 3087\u20133107                                               \n3087"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 119
encoding: FLOAT32
metadata:
{"title": "The aTSR Domain of Plasmodium Circumsporozoite Protein Bound Heparan Sulfates and Elicited High Titers of Sporozoite Binding Antibody After Displayed by Nanoparticles", "chroma:document": "3087\n\u00a9 2023 Xia et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php \nand incorporate the Creative Commons Attribution \u2013 Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work \nyou hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For \npermission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).\nInternational Journal of Nanomedicine                                                 \nDovepress\nopen access to scientific and medical research\nOpen Access Full Text Article\nReceived: 29 January 2023\nAccepted: 31 May 2023\nPublished: 8 June 2023"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 120
encoding: FLOAT32
metadata:
{"title": "Maximising sensitivity for detecting changes in protein expression: Experimental design using minimal CyDyes", "chroma:document": "REGULAR ARTICLE\nMaximising sensitivity for detecting changes in protein\nexpression: Experimental design using minimal CyDyes\nNatasha A. Karp and Kathryn S. Lilley\nDepartment of Biochemistry, Cambridge University, Cambridge, UK\nDIGE is a powerful tool for measuring changes in protein expression between samples. Here we\nassess the assumptions of normality and heterogeneity of variance that underlie the univariate\nstatistical tests routinely used to detect proteins with expression changes. Furthermore, the\ntechnical variance experienced in a multigel experiment is assessed here and found to be repro-\nducible within- and across-sample types. Utilising the technical variance measured, a power\nstudy is completed for several \u2018typical\u2019 fold changes in expression commonly used as thresholds\nby researchers. Based on this study using DeCyder, guidance is given on the number of gel\nreplicates that are needed for the experiment to have sufficient sensitivity to detect expression\nchanges. A two-dye system based on utilising just Cy3 and Cy5 was found to be more reproduci-\nble than the three-dye system. A power and cost-benefit analysis performed here suggests that\nthe traditional three-dye system would use fewer resources in studies where multiple samples\nare compared. Technical variance was shown to encompass both experimental and analytical\nnoise and thus is dependent on the analytical software utilised. Data is provided as a resource to\nthe community to assess alternative software and upgrades.\nReceived: February 15, 2005\nRevised: March 17, 2005\nAccepted: March 17, 2005\nKeywords:\nDIGE / Expression proteomics / Power / 2-DE / Variation\nProteomics 2005, 5, 3105\u20133115\n3105\n1\nIntroduction\n2-DE is a common method utilised to simultaneously sepa-\nrate and quantitate thousands of proteins to assess expres-\nsion changes in protein levels from one state to another.\nProteins are separated according to their pI and molecular\nweight. The resulting spot patterns can be visualised by pre-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 121
encoding: FLOAT32
metadata:
{"title": "Maximising sensitivity for detecting changes in protein expression: Experimental design using minimal CyDyes", "chroma:document": "labelling the sample prior to the separation, e.g. radioactivity\n[1], fluorescence [2\u20135] or post-separation with total protein\nstains such as colloidal CBB [6], SYPRO Ruby or deep purple\n[7, 8]. The gels are converted to digital images using scan-\nning devices and these images are processed to detect the\nspots, quantitate the spot volumes and match the spots pat-\nterns across different gels. Statistical methods are then\nemployed to detect protein spots with statistical significant\nchanges in expression.\nEarly comparative proteomics relied on using images\nfrom different gels. Gel-to-gel variation, however, led to\nproblematic detection and quantification of differences in\nprotein expression. A significant advancement in reproduci-\nbility was made by \u00dcnl\u00fc et al. [9] who multiplexed fluores-\ncently resolvable dyes (CyDyes) within a gel, which enabled\nthe comparison of multiple samples within the same gel. Gel\nrunning effects are thus comparable within the same gel\nallowing a more accurate comparison of spot volume. This\napproach has been commercialised by GE Healthcare (Swe-\nden) (formerly Amersham Bioscience). A multigel approach\nhas been demonstrated to significantly improve accuracy of\nquantitation by using one dye to label a standard sample that\nis present in every gel [10]. This standard sample is used to\nmatch the spot patterns across a gel series and to calculate a\nstandardised abundance (SA) value for a spot, which can\nthen be compared across many gels.\nCorrespondence: Dr. Kathryn Lilley, Department of Biochemistry,\nUniversity of Cambridge, Building O, Downing Site, Cambridge,\nCB2 1QW, UK\nE-mail: k.s.lilley@bioc.cam.ac.uk\nFax: 144-1223-333-345\nAbbreviations: ASB14, amidosulfobetaine-14; ECA, Erwinia caro-\ntovora; log10SA, log10(standardised abundance); SA, standard-\nised abundance\n\u00a9 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim\nwww.proteomics-journal.de\nDOI 10.1002/pmic.200500083"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 122
encoding: FLOAT32
metadata:
{"title": "Multi-omics analysis reveals the host\u0085microbe interactions in aged rhesus macaques", "chroma:document": "Frontiers in Microbiology\n01\nfrontiersin.org\nMulti-omics analysis reveals the \nhost\u2013microbe interactions in \naged rhesus macaques\nJue\u00a0Xu 1\u2020, Yue\u00a0Lan 2\u2020, Xinqi\u00a0Wang 2, Ke\u00a0Shang 2, Xu\u00a0Liu 3, \nJiao\u00a0Wang 2, Jing\u00a0Li 2, Bisong\u00a0Yue 3, Meiying\u00a0Shao 1* and \nZhenxin\u00a0Fan 2,3*\n1 West China School of Public Health and West China Fourth Hospital, Chengdu, Sichuan, China, \n2 Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life \nSciences, Sichuan University, Chengdu, China, 3 Sichuan Key Laboratory of Conservation Biology on \nEndangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, China\nAging is a complex multifactorial process that greatly affects animal health. \nMulti-omics analysis is widely applied in evolutionary biology and biomedical \nresearch. However, whether multi-omics can provide sufficient information to \nreveal comprehensive changes in aged non-human primates remains unclear. \nHere, we\u00a0explored changes in host\u2013microbe interactions with aging in Chinese \nrhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. \nResults showed marked changes in the oral and gut microbiomes between \nyoung and aged CRs, including significantly reduced probiotic abundance \nand increased pathogenic bacterial abundance in aged CRs. Notably, the \nabundance of Lactobacillus, which can metabolize tryptophan to produce aryl \nhydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, \nmetabolomics detected a decrease in the plasma levels of AhR ligands. In \naddition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic \nacid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, \nwhich may contribute to abnormal fatty acid metabolism and cardiovascular \ndisease. Transcriptome analysis identified changes in the expression of genes \nassociated with tryptophan metabolism and inflammation. In conclusion, \nmany potential links among different omics were found, suggesting that aged"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 123
encoding: FLOAT32
metadata:
{"title": "Multi-omics analysis reveals the host\u0085microbe interactions in aged rhesus macaques", "chroma:document": "CRs face multiple metabolic problems, immunological disorders, and oral \nand gut diseases. We\u00a0determined that tryptophan metabolism is critical for \nthe physiological health of aged CRs. Our findings demonstrate the value of \nmulti-omics analyses in revealing host\u2013microbe interactions in non-human \nprimates and suggest that similar approaches could be\u00a0applied in evolutionary \nand ecological research of other species.\nKEYWORDS\nnon-human primates, multi-omics, oral and gut microbiome, blood transcriptome \nand metabolome, aging\nTYPE Original Research\nPUBLISHED 27 September 2022\nDOI 10.3389/fmicb.2022.993879\nOPEN ACCESS\nEDITED BY\nZhigang Zhang,  \nYunnan University,  \nChina\nREVIEWED BY\nBinghua Sun,  \nAnhui University,  \nChina\nZhang Wang,  \nSouth China Normal University, China\n*CORRESPONDENCE\nMeiying Shao  \nshaomeiying2013@163.com  \nZhenxin Fan  \nzxfan@scu.edu.cn\n\u2020These authors have contributed equally to \nthis work\nSPECIALTY SECTION\nThis article was submitted to  \nEvolutionary and Genomic Microbiology,  \na section of the journal  \nFrontiers in Microbiology\nRECEIVED 14 July 2022\nACCEPTED 08 September 2022\nPUBLISHED 27 September 2022\nCITATION\nXu J, Lan Y, Wang X, Shang K, Liu X, Wang J, \nLi J, Yue B, Shao M and Fan Z (2022) Multi-\nomics analysis reveals the host\u2013microbe \ninteractions in aged rhesus macaques.\nFront. Microbiol. 13:993879.\ndoi: 10.3389/fmicb.2022.993879\nCOPYRIGHT\n\u00a9 2022 Xu, Lan, Wang, Shang, Liu, Wang, \nLi, Yue, Shao and Fan. This is an open-\naccess article distributed under the terms \nof the Creative Commons Attribution \nLicense (CC BY). The use, distribution or \nreproduction in other forums is permitted, \nprovided the original author(s) and the \ncopyright owner(s) are credited and that \nthe original publication in this journal is \ncited, in accordance with accepted \nacademic practice. No use, distribution or \nreproduction is permitted which does not \ncomply with these terms."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 124
encoding: FLOAT32
metadata:
{"title": "Influence of Sex on the Progression of Chronic Kidney Disease", "chroma:document": "In\ufb02uence of Sex on the Progression of\nChronic Kidney Disease\nJoel Neugarten, MD, and Ladan Golestaneh, MD\nCME Activity\nTarget Audience: The target audience for Mayo Clinic Proceedings is primar-\nily internal medicine physicians and other clinicians who wish to advance\ntheir current knowledge of clinical medicine and who wish to stay abreast\nof advances in medical research.\nStatement of Need: General internists and primary care physicians must\nmaintain an extensive knowledge base on a wide variety of topics covering\nall body systems as well as common and uncommon disorders. Mayo Clinic\nProceedings aims to leverage the expertise of its authors to help physicians\nunderstand best practices in diagnosis and management of conditions\nencountered in the clinical setting.\nAccreditation Statement:\nIn support of improving patient care, Mayo\nClinic College of Medicine and Science is\njointly accredited by the Accreditation Council\nfor Continuing Medical Education (ACCME),\nthe Accreditation Council for Pharmacy Educa-\ntion (ACPE), and the American Nurses Cre-\ndentialing\nCenter\n(ANCC)\nto\nprovide\ncontinuing education for the healthcare team.\nCredit Statements:\nAMA: Mayo Clinic College of Medicine and Science designates this journal-\nbased CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s).\u0001\nPhysicians should claim only the credit commensurate with the extent of\ntheir participation in the activity.\nMOC Credit Statement: Successful completion of this CME activity, which in-\ncludes participation in the evaluation component, enables the participant to\nearn up to 1 MOC point in the American Board of Internal Medicine\u2019s\n(ABIM) Maintenance of Certi\ufb01cation (MOC) program. Participants will earn\nMOC points equivalent to the amount of CME credits claimed for the activity.\nIt is the CME activity provider\u2019s responsibility to submit participant completion\ninformation to ACCME for the purpose of granting ABIM MOC credit.\nLearning Objectives: On completion of this article, you should be able to"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 125
encoding: FLOAT32
metadata:
{"title": "Influence of Sex on the Progression of Chronic Kidney Disease", "chroma:document": "(1) critically analyze the data that suggest that sex in\ufb02uences the progression\nof chronic kidney disease, (2) describe the effects of sex hormones on the\nrenin-angiotensin system, and (3) describe the effects of sex hormones on\nrenal physiology.\nDisclosures: As a provider accredited by ACCME, Mayo Clinic College of\nMedicine and Science (Mayo School of Continuous Professional Develop-\nment) must ensure balance, independence, objectivity, and scienti\ufb01c rigor\nin its educational activities. Course Director(s), Planning Committee mem-\nbers, Faculty, and all others who are in a position to control the content\nof this educational activity are required to disclose all relevant \ufb01nancial rela-\ntionships with any commercial interest related to the subject matter of the\neducational activity. Safeguards against commercial bias have been put in\nplace. Faculty also will disclose any off-label and/or investigational use of\npharmaceuticals or instruments discussed in their presentation. Disclosure\nof this information will be published in course materials so that those partic-\nipants in the activity may formulate their own judgments regarding the\npresentation.\nIn their editorial and administrative roles, Karl A. Nath, MBChB, Terry L.\nJopke, Kimberly D. Sankey, and Jenna M. Pederson, have control of the\ncontent of this program but have no relevant \ufb01nancial relationship(s)\nwith industry. Drs Neugarten and Golestaneh report no competing\ninterests.\nMethod of Participation: In order to claim credit, participants must com-\nplete the following:\n1. Read the activity.\n2. Complete the online CME Test and Evaluation. Participants must achieve\na score of 80% on the CME Test. One retake is allowed.\nVisit www.mayoclinicproceedings.org, select CME, and then select CME arti-\ncles to locate this article online to access the online process. On successful\ncompletion of the online test and evaluation, you can instantly download and\nprint your certi\ufb01cate of credit.\nEstimated Time: The estimated time to complete each article is approxi-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 126
encoding: FLOAT32
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{"title": "Influence of Sex on the Progression of Chronic Kidney Disease", "chroma:document": "mately 1 hour.\nHardware/Software: PC or MAC with Internet access.\nDate of Release: 7/1/2019\nExpiration Date: 6/30/2021 (Credit can no longer be offered after it has\npassed the expiration date.)\nPrivacy Policy: http://www.mayoclinic.org/global/privacy.html\nQuestions? Contact dletcsupport@mayo.edu.\nAbstract\nThe role that sex plays in the development and progression of chronic kidney disease remains a\nsubject of controversy. The lack of clarity in this important area re\ufb02ects complex interactions between\nbiological factors and cultural and socioeconomic in\ufb02uences that impact the relationship between sex\nand renal disease. Certainly, additional observational studies are indicated; however, innovative ap-\nproaches are required to isolate biological processes from cultural in\ufb02uences. Despite these limitations,\navailable data suggest that the progression of renal disease is slower in women than in men and that\nthis sexual dimorphism is primarily due to direct actions of sex hormones on cellular metabolism. The\nextent to which differences in lifestyle factors between the sexes in\ufb02uence sexual dimorphism in the\nprogression of chronic kidney disease remains to be elucidated.\n\u00aa 2019 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2019;94(7):1339-1356\nS\nex in\ufb02uences the incidence and prev-\nalence of many renal diseases as well\nas the rate of progression of these dis-\norders. In animal models of aging and cystic\nkidney disease and after renal ablation, male\nanimals have a worse renal prognosis than fe-\nmales.1 Manipulation of the hormonal envi-\nronment by gonadectomy or administration\nFrom the Albert Einstein\nCollege of Medicine, Renal\nDivision, Monte\ufb01ore\nMedical Center, Bronx,\nNY\nTHEMATIC REVIEW ON WOMEN\u2019S HEALTH\nMayo Clin Proc. n July 2019;94(7):1339-1356\nn https://doi.org/10.1016/j.mayocp.2018.12.024\nwww.mayoclinicproceedings.org n \u00aa 2019 Mayo Foundation for Medical Education and Research\n1339"}


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id: 127
encoding: FLOAT32
metadata:
{"title": "Circulating immune complexes in patients with ankylosing spondylitis", "chroma:document": "Annals of the Rheumatic Diseases, 1980, 39, 445-448\nCirculating immune complexes in patients with\nankylosing spondylitis\nG.\nS. PANAYI, J. SLANEY, AND B. D. WILLIAMS*\nFrom the Departments ofMedicine and Rheumatology, Guy's Hospital Medical School, London SE] 9RT\nSUMMARY\nEDTA plasma samples from 13 patients with ankylosing spondylitis (AS) were frac-\ntionated on Sephadex G-200 and the quantities of C3 and IgG within the first protein peak deter-\nmined by a sensitive haemagglutination-inhibition assay. Seven patients with AS had C3 detectable\nin the first peak and this was associated with an increased concentration of IgG in the corresponding\nfraction. These 7 patients had more active disease but did not have more peripheral arthritis. Our\nresults indicate that circulating immune complexes capable of initiating complement activation\nare present in the circulation of patients with ankylosing spondylitis.\nDespite the striking association between ankylosing\nspondylitis (AS) and HLA B27 the role of immuno-\nlogical factors in the pathogenesis of the disease is\nnot clear. Recently it has been proposed that AS\nmay be related\nin some way to infection with\nKlebsiella pneuomoniae,\na bacterium which may\npossess antigens cross-reacting with HLA B27.1\nOne way by which immune reactions may be\ninvolved in tissue damage in AS may be via the\ndeposition of immune complexes. In a previous\npaper we presented evidence that immune com-\nplexes are present in the circulation of patients with\nthis disease. The complexes were detected by the\ntechnique\nof\ninhibition\nof\nantibody-dependent\ncell-mediated cytotoxicity (ADCC).2 However, these\ncomplexes may not be of pathological importance,\nsince they may not activate the complement system.\nComplement activation is an important mechanism\nfor the induction of inflammation. There is some\nevidence that activation does occur in AS, since raised\nserum levels of C3 and C4 inactivation products\nhave been noted.3 We therefore decided to investi-\ngate this possibility by measuring the amount of"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 128
encoding: FLOAT32
metadata:
{"title": "Circulating immune complexes in patients with ankylosing spondylitis", "chroma:document": "macromolecular C3 in EDTA-plasma of AS patients\nas evidence of complexed or activated complement.\nMaterials and methods\nPATIENTS\nThirteen patients with AS were studied. The duration\nof disease, presence of morning stiffness, inflam-\nAccepted for publication 14 September 1979\nCorrespondence to Dr G. S. Panayi,\n*Present address, Department of Medicine, Royal Post-\ngraduate Medical School, Ducane Road, London W13.\nmation in peripheral joints, and the erythrocyte\nsedimentation rate were noted. All patients were\nHLA B27 positive. None had active uveitis at the\ntime of study.\nLABORATORY METHODS\nCollection and storage ofplasma. Blood was collected\ninto EDTA (final concentration 0.01M), rapidly\nseparated,\naliquoted,\nand\nthe\nplasma\nsamples\nstored at -700C until used.\nMacromolecular C3 assay (MMC3). Details of\nthis method have already been published.4 Briefly,\nthe method consists of fractionating EDTA-plasma\non Sephadex G-200. The presence of MMC3\nis\nindicated by a change in distribution in C3 with its\nappearance within the first peak of G-200 eluted\nfractions.\nPlasma C3 and C4 levels. These were determined\nby\nradial\nimmunodiffusion\nusing\nmonospecific\nanti-sera and results expressed as a percentage of a\npool of normal plasma.\nDetection ofIgG. The concentration of IgG in the\nvarious Sephadex G-200 fractions was determined\nby a microhaemagglutination assay. Washed, group\nO rhesus\npositive human red blood\ncells were\nsensitised with human anti-D serum and after 2\nwashings in Veronal-buffered saline were resuspended\nat 0\n- 5% concentration. Sephadex G-200 eluted\nplasma fractions were serially diluted with buffer\nin plastic microtitre microagglutination trays, and\nan equal volume of an appropriate dilution of an\nanti-IgG antiserum (containing 2 minimum agglu-\ntinating doses) was added. After incubation at room\ntemperature for 60 minutes the sensitised cells were\n445"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 129
encoding: FLOAT32
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{"title": "Journal Cellular Physiology - 2019 - Hu - Region\u2010resolved proteomics profiling of monkey heart", "chroma:document": "Received: 18 July 2018 |\nAccepted: 6 December 2018\nDOI: 10.1002/jcp.28052\nO R I G I N A L R E S E A R C H A R T I C L E\nRegion\u2010resolved proteomics profiling of monkey heart\nHao\u2010Liang Hu1*\n| Yu Kang2* | Yong Zeng1* | Ming Zhang3 | Qiong Liao1 |\nMing\u2010Qiang Rong1\n| Qin Zhang2 | Ren Lai3\n1The National & Local Joint Engineering\nLaboratory of Animal Peptide Drug\nDevelopment, College of Life Sciences, Hunan\nNormal University, Changsha, China\n2Division of Cardiology, West China Hospital,\nSichuan University, Chengdu, Sichuan, China\n3Key Laboratory of Animal Models and Human\nDisease Mechanisms of Chinese Academy of\nSciences &Yunnan Province, Kunming\nInstitute of Zoology, Chinese Academy of\nSciences (CAS), Kunming, Yunnan, China\nCorrespondence\nMing\u2010Qiang Rong, The National & Local Joint\nEngineering Laboratory of Animal Peptide\nDrug Development, College of Life Sciences,\nHunan Normal University, 410081 Changsha,\nChina.\nEmail: rongmq@hunnu.edu.cn\nQin Zhang, Cardiology Division, West China\nHospital, Sichuan University, Chengdu,\n610041 Sichuan, China.\nEmail: qzhang2000cn@163.com\nRen Lai, Key Laboratory of Animal Models and\nHuman Disease Mechanisms of Chinese\nAcademy of Sciences &Yunnan Province,\nKunming Institute of Zoology, Chinese\nAcademy of Sciences (CAS), 650223 Kunming,\nYunnan, China.\nEmail: rlai@mail.kiz.ac.cn\nFunding information\nNational Natural Science Foundation of China,\nGrant/Award Numbers: 81573320, 81470508\nAbstract\nNonhuman primates (NHPs) play an indispensable role in biomedical research\nbecause of their similarities in genetics, physiological, and neurological function to\nhumans. Proteomics profiling of monkey heart could reveal significant cardiac\nbiomarkers and help us to gain a better understanding of the pathogenesis of heart\ndisease. However, the proteomic study of monkey heart is relatively lacking. Here, we\nperformed the proteomics profiling of the normal monkey heart by measuring three\nmajor anatomical regions (vessels, valves, and chambers) based on iTRAQ\u2010coupled"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 130
encoding: FLOAT32
metadata:
{"title": "Journal Cellular Physiology - 2019 - Hu - Region\u2010resolved proteomics profiling of monkey heart", "chroma:document": "LC\u2010MS/MS analysis. Over 3,200 proteins were identified and quantified from three\nheart tissue samples. Furthermore, multiple bioinformatics analyses such as gene\nontology analysis, protein\u2013protein interaction analysis, and gene\u2010diseases association\nwere used to investigate biological network of those proteins from each area. More\nthan 60 genes in three heart regions are implicated with heart diseases such as\nhypertrophic cardiomyopathy, heart failure, and myocardial infarction. These genes\nassociated with heart disease are mainly enriched in citrate cycle, amino acid\ndegradation, and glycolysis pathway. At the anatomical level, the revelation of\nmolecular characteristics of the healthy monkey heart would be an important starting\npoint to investigate heart disease. As a unique resource, this study can serve as a\nreference map for future in\u2010depth research on cardiac disease\u2010related NHP model\nand novel biomarkers of cardiac injury.\nK E Y W O R D S\nbioinformatics analysis, gene\u2010disease associations, monkey heart, proteomics\n1\n|\nINTRODUCTION\nThe heart, which composed of vessels, valves, and chambers, pumps\nadequate blood to organs and tissues, then provides oxygen and\nnutrients to the whole body, as well as assists in the removal of\nmetabolic wastes. Periodic dilatation and contraction of the heart is\ncaused by a complicated interaction between biological electrocar-\ndiac signals and mechanical forces (Kwon et al., 2016). The heart\nvessels consist largely of endothelium, vascular smooth muscle and\nadventitia. The four valves open or close precisely on differential\nblood pressure, which is mainly made up of endothelial cells (ECs)\nand interstitial cells (ICs; Liu, Joag, & Gotlieb, 2007; Taylor, Batten,\nBrand, Thomas, & Yacoub, 2003). The atria and ventricles are divided\nby valves to prevent blood reflux, and the principal cell type of the\nheart chambers is cardiomyocytes (CMs). Besides, cardiac fibroblasts\n(CFs) produce the extracellular matrix (ECM) scaffold of the heart"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 131
encoding: FLOAT32
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{"title": "Journal Cellular Physiology - 2019 - Hu - Region\u2010resolved proteomics profiling of monkey heart", "chroma:document": "and are estimated to constitute more than half of total heart cells\n(Bergmann et al., 2015).\nCardiovascular\ndisease\nis\none\nof\nthe\nleading\ncauses\nof\nmortality. The inflammatory reaction in the vessel walls is working\nto promote atherosclerosis (Bryan et al., 2014; Gimbrone &\nGarcia\u2010Cardena, 2016; McAlpine & Swirski, 2016). Valve disorder,\nJ Cell Physiol. 2019;234:13720\u201313734.\nwileyonlinelibrary.com/journal/jcp\n13720\n|\n\u00a9 2019 Wiley Periodicals, Inc.\n*These authors contributed equally to this work.\n 10974652, 2019, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jcp.28052 by Westlake University, Wiley Online Library on [09/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 132
encoding: FLOAT32
metadata:
{"title": "Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants", "chroma:document": "ARTICLE\nLong-read assembly of the Chinese rhesus\nmacaque genome and identi\ufb01cation of ape-speci\ufb01c\nstructural variants\nYaoxi He1,2,3,4,8, Xin Luo1,2,3,4,8, Bin Zhou1,2,3,4,8, Ting Hu1,2,3,4,8, Xiaoyu Meng\n1,2,3,4,8, Peter A. Audano5,\nZev N. Kronenberg5, Evan E. Eichler\n5,6, Jie Jin\n7, Yongbo Guo1,2,3,4, Yanan Yang1,2, Xuebin Qi\n1,2,3 &\nBing Su1,2,3\nWe present a high-quality de novo genome assembly (rheMacS) of the Chinese rhesus\nmacaque (Macaca mulatta) using long-read sequencing and multiplatform scaffolding\napproaches. Compared to the current Indian rhesus macaque reference genome (rheMac8),\nrheMacS increases sequence contiguity 75-fold, closing 21,940 of the remaining assembly\ngaps (60.8 Mbp). We improve gene annotation by generating more than two million full-\nlength transcripts from ten different tissues by long-read RNA sequencing. We sequence\nresolve 53,916 structural variants (96% novel) and identify 17,000 ape-speci\ufb01c structural\nvariants (ASSVs) based on comparison to ape genomes. Many ASSVs map within ChIP-seq\npredicted enhancer regions where apes and macaque show diverged enhancer activity and\ngene expression. We further characterize a subset that may contribute to ape- or great-ape-\nspeci\ufb01c phenotypic traits, including taillessness, brain volume expansion, improved manual\ndexterity, and large body size. The rheMacS genome assembly serves as an ideal reference\nfor future biomedical and evolutionary studies.\nhttps://doi.org/10.1038/s41467-019-12174-w\nOPEN\n1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. 2 Primate\nResearch Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. 3 Center for Excellence in Animal Evolution and\nGenetics, Chinese Academy of Sciences, Kunming 650223, China. 4 Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 133
encoding: FLOAT32
metadata:
{"title": "Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants", "chroma:document": "100101, China. 5 Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. 6 Howard Hughes Medical\nInstitute, University of Washington, Seattle, WA 98195, USA. 7 Nextomics Biosciences, Wuhan 430000, China. 8These authors contributed equally: Yaoxi\nHe, Xin Luo, Bin Zhou, Ting Hu, and Xiaoyu Meng. Correspondence and requests for materials should be addressed to B.S. (email: sub@mail.kiz.ac.cn)\nNATURE COMMUNICATIONS |   (2019) 10:4233 | https://doi.org/10.1038/s41467-019-12174-w | www.nature.com/naturecommunications\n1\n1234567890():,;"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 134
encoding: FLOAT32
metadata:
{"title": "Microsoft Word - Sup_Materials_GTEx_Transcriptome_May1st.2015_MM.docx", "chroma:document": "www.sciencemag.org/content/348/6235/660/suppl/DC1 \n \n \n \n \nSupplementary Materials for \n \nThe human transcriptome across tissues and individuals \n \nMarta Mel\u00e9, Pedro G. Ferreira, Ferran Reverter, David S. DeLuca, Jean Monlong, \nMichael Sammeth, Taylor R. Young, Jakob M Goldmann, Dmitri D. Pervouchine, \nTimothy J. Sullivan, Rory Johnson, Ayellet V. Segr\u00e8, Sarah Djebali, Anastasia Niarchou, \nThe GTEx Consortium, Fred A. Wright, Tuuli Lappalaienen, Miquel Calvo, Gad Getz, \nEmmanouil Dermitzakis, Kristin G. Ardlie,* Roderic Guig\u00f3* \n \n*Corresponding author. E-mail: kardlie@broadinstitute.org (K.G.A.); roderic.guigo@crg.cat (R.G.) \n \nPublished 8 May 2015, Science 348, 660 (2015) \nDOI: 10.1126/science.aaa0355 \n \nThis PDF file includes: \n \nMaterials and Methods \nFigs. S1 to S25 \nTables S1 to S20 \nCaptions for data tables S4 to S7 and S9 to S18"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 135
encoding: FLOAT32
metadata:
{"title": "Adipose tissue: Sex differences in adipogenesis", "chroma:document": "The mechanisms underlying the \ndifferent distribution of adipose \ntissue in men and women are unclear. \nNew research in mice sheds some \nlight on this issue.\nMen are more likely to \naccumulate visceral white adipose \ntissue (VWAT), which has negative \nconsequences for metabolic health, \nwhereas women are more likely to \naccumulate subcutaneous white \nadipose tissue (SWAT), which is \nthought to be protective. To \ninvestigate the mechanisms \nunderlying this difference, a team  \nof researchers led by Matthew \nRodeheffer developed an in\u00a0vivo \nadipogenesis assay to study how fat \nmass expands in mice. \u201cFocusing on \nin\u00a0vivo assays is critical for the study \nof adipose given the responsiveness of  \nadipose tissue to nutritional and \nhormonal cues and it\u2019s integration \ninto whole-body physiology,\u201d \nexplains Rodeheffer.\nThe investigators found that \nobesity as a result of a high-fat diet \ninduces adipocyte hyperplasia in just \nthe VWAT of male mice. By contrast, \nthe same conditions resulted in \nadipocyte hyperplasia in both VWAT \nand SWAT in female mice. \u201cThese \ndepot-dependent differences in \nadipogenesis are influenced by the \ntissue microenvironment in the \ndifferent depots, not by cell-intrinsic \ndifferences in adipocyte precursors,\u201d \nsays Rodeheffer.\nOvariectomized female mice had a \nmale-like response to a high-fat diet, \nwhich suggests that sex hormones \nmight be involved in the differences in \nadipogenesis between the sexes. To \ntest this idea, the researchers \nadministered oestrogen to male mice. \nWhen these mice were fed a high-fat \ndiet, adipocyte hyperplasia was \nincreased in the SWAT, which indicates \nthat oestrogen influences the \nresponse of SWAT to a high-fat diet. \n\u201cNow that we have characterized \nadipocyte hyperplasia in obesity at the \ncellular level, we are focusing on how \ndietary changes drive obesogenic \nadipogenesis and what components of \nthe adipose tissue microenvironment \ninfluence adipocyte hyperplasia in \nobesity,\u201d concludes Rodeheffer.\nClaire Greenhill\n ADIPOSE TISSUE"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 136
encoding: FLOAT32
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{"title": "Adipose tissue: Sex differences in adipogenesis", "chroma:document": "Sex differences in adipogenesis\nORIGINAL ARTICLE Jeffery, E. et\u00a0al. The adipose \ntissue microenvironment regulates depot-specific \nadipogenesis in obesity. Cell Metab. http://dx.doi.\norg/10.1016/j.cmet.2016.05.012 (2016)\nFURTHER READING Karpe, F. & Pinnick, K. E. \nBiology of upper-body and lower-body adipose \ntissue\u2014link to whole-body phenotypes. Nat. Rev. \nEndocrinol. 11, 90\u2013100 (2015)\nRESEARCH HIGHLIGHTS\nNATURE REVIEWS | ENDOCRINOLOGY \n www.nature.com/nrendo\nNature Reviews Endocrinology | Published online 1 Jul 2016; doi:10.1038/nrendo.2016.109\n\u00a9\n \n2016\n \nM\nacm\nillan\n \nPublishers\n \nLim\nited.\n \nAll\n \nrights\n \nreserved."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 137
encoding: FLOAT32
metadata:
{"title": "Mass spectrometry-based draft of the mouse proteome", "chroma:document": "ResouRce\nhttps://doi.org/10.1038/s41592-022-01526-y\n1Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany. 2College of Life Science, Northwest University, Xi\u2019an, China. \n3Bavarian Biomolecular Mass Spectrometry Center, Technical University of Munich, Freising, Germany. 4Division of Translational Cancer Research, German \nCancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. 5Chair of Translational Cancer Research and Institute for \nExperimental Cancer Therapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. 6Department of Internal \nMedicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 7Center for Translational Cancer Research (TranslaTUM), School \nof Medicine, Technical University of Munich, Munich, Germany. 8Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of \nMunich, Munich, Germany. 9Institute of Radiation Medicine, Department of Radiation Sciences, Helmholtz Zentrum M\u00fcnchen, Neuherberg, Germany. \n10German Cancer Consortium (DKTK), Munich, Germany. 11German Cancer Research Center (DKFZ), Heidelberg, Germany. 12Population epigenetics \nand epigenomics, Technical University of Munich, Freising, Germany. 13Institute of Advanced Study (IAS), Technical University of Munich, Freising, \nGermany. 14Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental \nHealth, Neuherberg, Germany. 15Institute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich, Munich, \nGermany. 16Medical Clinic and Policlinic II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 17Chair of Experimental Genetics, \nTUM School of Life Sciences, Technical University of Munich, Freising, Germany. 18German Center for Diabetes Research (DZD), Neuherberg, Germany."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 138
encoding: FLOAT32
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{"title": "Mass spectrometry-based draft of the mouse proteome", "chroma:document": "19Computational Mass Spectrometry, Technical University of Munich, Freising, Germany. 20University Medical Center G\u00f6ttingen, Department of  \nGeneral, Visceral and Pediatric Surgery, G\u00f6ttingen, Germany. 21These authors contributed equally: Piero Giansanti, Patroklos Samaras, Yangyang Bian. \n\u2709e-mail: kuster@tum.de\nT\nhe mouse is arguably among the most important mamma-\nlian model systems for basic, translational and biomedical \nresearch1. The initial sequencing of the mouse genome in \n2002 as well as systematic transcriptome analyses of mouse tissues \nin 2004 marked important milestones as these provided impor-\ntant informational tools to better understand the human genome \nand human (patho-)physiology2,3. As most biological processes are \ncontrolled by proteins and their posttranslational modifications \n(PTMs), adding a proteomic dimension is a logical consequence. An \ninitial analysis of 28 mouse tissues provided evidence for roughly \n7,300 proteins and an earlier phosphoproteomic investigation iden-\ntified roughly 36,000 phosphorylation sites (p-sites) in nine tis-\nsues4,5. Here, we substantially extend these efforts by analyzing the \nproteomes and phosphoproteomes of 41 adult tissues of C57BL/6N \nmice covering 15 major anatomical systems and 66 KrasG12D pancre-\natic ductal adenocarcinoma (PDAC) cell lines using a quantitative \nmass spectrometry (MS)-based approach (Fig. 1a).\nResults\nA high-quality map of the mouse proteome. Following state-of- \nthe-art protocols for protein identification and error propaga-\ntion control (Methods), we identified 17,883 proteins (17,771 \nand 12,971 from tissues and cell lines, respectively) representing \n16,995 of the 22,437 protein-coding genes annotated in UniProtKB  \n(Fig. 1b and Supplementary Table 1). The phosphoproteomes  \n(Fig. 1c,d and Supplementary Table 2) covered 40,562 and 22,113 \nMass spectrometry-based draft of the mouse \nproteome\nPiero Giansanti\u200a \u200a1,21, Patroklos Samaras\u200a \u200a1,21, Yangyang Bian\u200a \u200a1,2,21, Chen Meng3, Andrea Coluccio4,5,6,7,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 139
encoding: FLOAT32
metadata:
{"title": "Mass spectrometry-based draft of the mouse proteome", "chroma:document": "Martin Frejno\u200a \u200a1, Hannah Jakubowsky4,5,6,7, Sophie Dobiasch8,9,10,11, Rashmi R. Hazarika12,13, \nJulia Rechenberger\u200a \u200a1, Julia Calzada-Wack14, Johannes Krumm1, Sebastian Mueller6,7,15, \nChien-Yun Lee\u200a \u200a1, Nicole Wimberger\u200a \u200a4,5,6,7, Ludwig Lautenbacher\u200a \u200a1, Zonera Hassan16, \nYun-Chien Chang1, Chiara Falcomat\u00e04,5,6,7, Florian P. Bayer1, Stefanie B\u00e4rthel\u200a \u200a4,5,6,7, Tobias Schmidt\u200a \u200a1,  \nRoland Rad4,6,7,15, Stephanie E. Combs8,9,10,11, Matthew The1, Frank Johannes12,13, Dieter Saur\u200a \u200a4,5,6,7,  \nMartin Hrabe de Angelis\u200a \u200a14,17,18, Mathias Wilhelm\u200a \u200a1,19, G\u00fcnter Schneider\u200a \u200a16,20 and \nBernhard Kuster\u200a \u200a1,3,10,11,13\u2009\u2709\nThe laboratory mouse ranks among the most important experimental systems for biomedical research and molecular refer-\nence maps of such models are essential informational tools. Here, we present a quantitative draft of the mouse proteome and \nphosphoproteome constructed from 41 healthy tissues and several lines of analyses exemplify which insights can be gleaned \nfrom the data. For instance, tissue- and cell-type resolved profiles provide protein evidence for the expression of 17,000 genes, \nthousands of isoforms and 50,000 phosphorylation sites in vivo. Proteogenomic comparison of mouse, human and Arabidopsis \nreveal common and distinct mechanisms of gene expression regulation and, despite many similarities, numerous differentially \nabundant orthologs that likely serve species-specific functions. We leverage the mouse proteome by integrating phenotypic \ndrug (n\u2009>\u2009400) and radiation response data with the proteomes of 66 pancreatic ductal adenocarcinoma (PDAC) cell lines \nto reveal molecular markers for sensitivity and resistance. This unique atlas complements other molecular resources for the \nmouse and can be explored online via ProteomicsDB and PACiFIC.\nNATuRE METHoDS | www.nature.com/naturemethods"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 140
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{"title": "Mass-spectrometry-based draft of the Arabidopsis proteome", "chroma:document": "Nature | www.nature.com | 1\nArticle\nMass-spectrometry-based draft of the \nArabidopsis proteome\nJulia Mergner1, Martin Frejno1, Markus List2, Michael Papacek3, Xia Chen4, Ajeet Chaudhary4, \nPatroklos Samaras1, Sandra Richter5, Hiromasa Shikata6,7, Maxim Messerer8, Daniel Lang8, \nStefan Altmann9, Philipp Cyprys10, Daniel P. Zolg1, Toby Mathieson11, Marcus Bantscheff11, \nRashmi R. Hazarika12,13, Tobias Schmidt1, Corinna Dawid14, Andreas Dunkel14,  \nThomas Hofmann14, Stefanie Sprunck10, Pascal Falter-Braun9,15, Frank Johannes12,13,  \nKlaus F. X. Mayer8,16, Gerd J\u00fcrgens5, Mathias Wilhelm1, Jan Baumbach2, Erwin Grill3,  \nKay Schneitz4, Claus Schwechheimer6 & Bernhard Kuster1,13,17\u2009\u2709\nPlants are essential for life and are extremely diverse organisms with unique \nmolecular capabilities1. Here we present a quantitative atlas of the transcriptomes, \nproteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis \nthaliana. Our analysis provides initial answers to how many genes exist as proteins \n(more than 18,000), where they are expressed, in which approximate quantities  \n(a dynamic range of more than six orders of magnitude) and to what extent they are \nphosphorylated (over 43,000 sites). We present examples of how the data may be \nused, such as to discover proteins that are translated from short open-reading frames, \nto uncover sequence motifs that are involved in the regulation of protein production, \nand to identify tissue-specific protein complexes or phosphorylation-mediated \nsignalling events. Interactive access to this resource for the plant community is \nprovided by the ProteomicsDB and ATHENA databases, which include powerful \nbioinformatics tools to explore and characterize Arabidopsis proteins, their \nmodifications and interactions.\nThe plant model organism A. thaliana has revolutionized our under-\nstanding of plant biology and influenced many other areas of the life \nsciences1. Knowledge derived from Arabidopsis has also provided mech-"}


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{"title": "Mass-spectrometry-based draft of the Arabidopsis proteome", "chroma:document": "anistic understanding of important agronomic traits in crop species2. \nThe Arabidopsis genome was sequenced 20\u00a0years ago, and hundreds of \nnatural variants have since been analysed at the genome and epigenome \nlevel3,4. By contrast, the Arabidopsis proteome as the main executer of \nmost biological processes is far less comprehensively characterized. To \naddress this gap, we used state-of-the-art mass spectrometry and RNA \nsequencing (RNA-seq) analyses to provide the first, to our knowledge, \nintegrated proteomic, phosphoproteomic and transcriptomic atlas of \nArabidopsis. We use select examples to show how this rich molecular \nresource can be used to explore the function of single proteins or entire \npathways across several omics levels.\nMulti-omics atlas of Arabidopsis\nWe generated an expression atlas covering, on average, 17,603\u00a0\u00b1\u00a01,317 \n(mean\u00a0\u00b1 s.d.) transcripts, 14,430\u00a0\u00b1\u00a0911 proteins and 14,689\u00a0\u00b1\u00a02,509 \nphosphorylation sites (P-sites) per tissue, using a reproducible bio-\nchemical and analytical approach (Fig.\u00a01a, b, Extended Data Fig.\u00a01a\u2013c, \nSupplementary Data\u00a01, 2). In total, the protein abundance data cover \n18,210 out of the 27,655 protein-coding genes (66%) annotated in Ara-\nport115. This is a substantial increase compared with the percentage of \ngenes with evidence at the protein level reported in UniProt (27%)6, and \nmore than double the number of proteins identified in an earlier tissue \nproteome analysis7 (Fig.\u00a01c, Extended Data Fig.\u00a01d\u2013f). In addition, we \nreport tissue-resolved quantitative evidence for a total of 43,903 P-sites, \nmaking this study one of the most comprehensive single Arabidopsis \nphosphoproteomes published so far (Fig.\u00a01c). We found that 47% of the \nexpressed proteome was phosphorylated in at least one instance, con-\nfirming earlier analyses of individual phosphoproteomes or informa-\ntion assembled in the PhosPhAT database8,9 (Extended Data Fig.\u00a01g, h).  \nThe actual figures in plantae are likely to be considerably higher as"}


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id: 142
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{"title": "Mass-spectrometry-based draft of the Arabidopsis proteome", "chroma:document": "there is limited overlap between these data sources. This can be readily \nexplained by technical factors (such as insufficient sequence cover-\nage) and, more importantly, differences in plant genotypes or stimuli \nthat influence phosphorylation. The above figures are similar to those \nhttps://doi.org/10.1038/s41586-020-2094-2\nReceived: 4 June 2019\nAccepted: 17 January 2020\nPublished online: xx xx xxxx\n Check for updates\n1Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), Freising, Germany. 2Chair of Experimental Bioinformatics, Technical University of Munich (TUM), Freising, Germany. \n3Chair of Botany, Technical University of Munich (TUM), Freising, Germany. 4Plant Developmental Biology, Technical University of Munich (TUM), Freising, Germany. 5Center for Plant Molecular \nBiology, University of T\u00fcbingen, T\u00fcbingen, Germany. 6Chair of Plant Systems Biology, Technical University of Munich (TUM), Freising, Germany. 7Devision of Plant Environmental Responses, \nNational Institute for Basic Biology, Okazaki, Japan. 8Plant Genome and Systems Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich-Neuherberg, \nGermany. 9Institute of Network Biology (INET), Helmholtz Center Munich, German Research Center for Environmental Health, Munich-Neuherberg, Germany. 10Cell Biology and Plant \nBiochemistry, University of Regensburg, Regensburg, Germany. 11Cellzome GmbH, Heidelberg, Germany. 12Population Epigenetics and Epigenomics, Technical University of Munich (TUM), \nFreising, Germany. 13Institute of Advanced Study (IAS), Technical University of Munich (TUM), Freising, Germany. 14Chair of Food Chemistry and Molecular Sensory Science, Technical University \nof Munich (TUM), Freising, Germany. 15Chair of Microbe-Host Interactions, Ludwigs-Maximilians-University (LMU), Munich, Germany. 16Plant Genome Biology, Technical University of Munich"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 143
encoding: FLOAT32
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{"title": "Mass-spectrometry-based draft of the Arabidopsis proteome", "chroma:document": "(TUM), Freising, Germany. 17Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), Technical University of Munich (TUM), Freising, Germany. \u2709e-mail: kuster@tum.de"}


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id: 144
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{"title": "Mass-spectrometry-based draft of the human proteome", "chroma:document": "ARTICLE\ndoi:10.1038/nature13319\nMass-spectrometry-based draft of the\nhuman proteome\nMathias Wilhelm1,2*, Judith Schlegl2*, Hannes Hahne1*, Amin Moghaddas Gholami1*, Marcus Lieberenz2, Mikhail M. Savitski3,\nEmanuel Ziegler2, Lars Butzmann2, Siegfried Gessulat2, Harald Marx1, Toby Mathieson3, Simone Lemeer1, Karsten Schnatbaum4,\nUlf Reimer4, Holger Wenschuh4, Martin Mollenhauer5, Julia Slotta-Huspenina5, Joos-Hendrik Boese2, Marcus Bantscheff3,\nAnja Gerstmair2, Franz Faerber2 & Bernhard Kuster1,6\nProteomesarecharacterized bylarge protein-abundancedifferences, cell-type- and time-dependentexpression patterns\nand post-translational modifications, all of which carry biological information that is not accessible by genomics or tran-\nscriptomics. Here we present a mass-spectrometry-based draft of the human proteome and a public, high-performance,\nin-memory database for real-time analysis of terabytes of big data, called ProteomicsDB. The information assembled from\nhumantissues,celllinesandbodyfluidsenabledestimationofthesizeoftheprotein-coding genome, andidentifiedorgan-\nspecific proteins and a large number of translated lincRNAs (long intergenic non-coding RNAs). Analysis of messenger\nRNA and protein-expression profiles ofhuman tissues revealedconserved controlofproteinabundance, and integrationof\ndrug-sensitivity data enabled the identification of proteins predicting resistance or sensitivity. The proteome profiles also\nhold considerable promise for analysing the composition and stoichiometry of protein complexes. ProteomicsDB thus\nenables navigation of proteomes, provides biological insight and fosters the development of proteomic technology.\nThelarge-scaleinterrogationofbiologicalsystemsbymass-spectrometry-\nbased proteomics provides insights into protein abundance, cell-type\nand time-dependent expression patterns, post-translational modifica-\ntions (PTMs) and protein\u2013protein interactions, all of which carry bio-\nlogicalinformationthatisbest investigated attheproteinlevel.Perhaps"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 145
encoding: FLOAT32
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{"title": "Mass-spectrometry-based draft of the human proteome", "chroma:document": "surprisingly,itisstillnotclearwhichofthe19,629humangenesannotated\nin Swiss-Prot1 (20,493 in UniProt) are translated into proteins. Therefore,\nmajor efforts are underway to identify these genes, including the Human\nProteomeProject(HPP),whichaimstobroadlycharacterizethehuman\nproteome, the Human Protein Atlas project (HPA), which seeks to gen-\nerate antibodiesfor allhuman proteins, and theProteomeXchange con-\nsortium,whichfacilitates thegatheringandsharingofproteomic data2\u20134.\nDespite the fact that a plethora of individual human proteomic studies\nexist, only a few systematic efforts to assemble and characterize human\nproteomeshave beenreported so far5,6. In part this is because most pro-\nteomic data do not reside in public repositories, proteomic data annota-\ntion is often sketchy, and the data generation and processing platforms\nare of varying capability, performance and maturity. Importantly, there\nis alsoa notable challenge in making \u2018big data\u2019 (that is, large amounts of\ndata that are difficult or impossible to process using traditional techno-\nlogyandalgorithms)morewidelyaccessibletothescientificcommunity,\nbecause the development of scalable analysis tools is only in its infancy.\nAssembly of the proteome in ProteomicsDB\nHere we present a draft of the human proteome assembled using data\nfrom 16,857 liquid chromatography tandem-mass-spectrometry (LC-\nMS/MS) experiments involving human tissues, cell lines, body fluids,\naswellasdatafromPTMstudiesandaffinitypurifications.Wealsopres-\nenttheanalysisoftheassembleddata,inProteomicsDB,anin-memory\ndatabase designed for the real-time analysis of big data (https://www.\nproteomicsdb.org).Forthisstudy (Fig. 1a), wecombined dataavailable\nfromrepositoriesandotherwisecontributedbycolleagues(60%oftotal)\nwith published as well as new data from the authors\u2019 laboratories (40%\nof total; Supplementary Table 1 and Supplementary Information). To\nmaximize proteome coverage, we reprocessed all experiments using\nMaxQuant7 and Mascot8, and the resulting 1.1-billion peptide spec-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 146
encoding: FLOAT32
metadata:
{"title": "Mass-spectrometry-based draft of the human proteome", "chroma:document": "trummatches(PSMs)wereimportedintoProteomicsDB.Thedatabase\n(Fig. 1b) comprisesa publicrepository, a webinterface featuring several\ndata views and analysis tools, and an application programming inter-\nface (API). At the heart of ProteomicsDB is an \u2018in-memory\u2019 computa-\ntionalresourcecommanding2terabytes(TB)ofrandomaccessmemory\n(RAM)and160centralprocessorunits(CPUs),whichenablesthestorage\nof alldata in the main memory,all of the time. This makes computational\ntasks very efficient, illustrated by the capability to display and annotate\nany of the approximately 71-million currently identified peptide-mass\nspectra in real time (Extended Data Fig. 1). Controlling the quality of\npeptide and protein identifications is important but exactly how this is\nbest accomplished is still debated in the community9,10. For the current\nassemblyoftheproteome,wereliedonhighresolutionmass-spectrometry\ndatatokeepfalseidentificationslow.Weappliedatwo-stepfilteringprocess,\nfirstbycontrollingthefalsediscoveryrate(FDR)at1%forPSMsgenerated\nby each LC-MS/MS experiment using a global target-decoy approach11.\nPeptide identifications then had to pass a length-dependent Mascot or\nAndromedascorethresholdof5%localFDRonthetotalaggregateddata\nand we categorically rejected all peptides shorter than seven amino acids\n(Extended Data Figs 1 and 2, and Supplementary Information). Com-\nparison to 27 published studies shows thatthisschemeisinlinewith the\noften-used 1% protein FDR criterion (Supplementary Table 1) and avoids\nthe unsolved issue of artificially high protein FDRs when analysing large\ndata sets12 (Extended Data Fig. 2 and Supplementary Information).\nProteomic annotation of the genome\nAt the time of writing, ProteomicsDB held protein evidence for 18,097\nof the 19,629 human genes annotated in Swiss-Prot (92%) as well as\n*These authors contributed equally to this work."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 147
encoding: FLOAT32
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{"title": "Mass-spectrometry-based draft of the human proteome", "chroma:document": "1Chair of Proteomics and Bioanalytics, Technische Universita\u00a8t Mu\u00a8nchen, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany. 2SAP AG, Dietmar-Hopp-Allee 16, 69190 Walldorf, Germany. 3Cellzome\nGmbH, Meyerhofstra\u00dfe 1, 69117 Heidelberg, Germany. 4JPT Peptide Technologies GmbH, Volmerstra\u00dfe 5, 12489 Berlin, Germany. 5Institute of Pathology, Technische Universita\u00a8t Mu\u00a8nchen, Trogerstra\u00dfe\n18, 81675 Mu\u00a8nchen, Germany. 6Center for Integrated Protein Science Munich, Germany.\n5 8 2 |\nN A T U R E\n| V O L 5 0 9\n| 2 9\nM A Y 2 0 1 4\n\u00a92014 Macmillan Publishers Limited. All rights reserved"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 148
encoding: FLOAT32
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{"title": "Multilayered omics reveal sex- and depot-dependent adipose progenitor cell heterogeneity", "chroma:document": "Resource\nMultilayered omics reveal sex- and depot-dependent\nadipose progenitor cell heterogeneity\nGraphical abstract\nHighlights\nd Integrated multilayer omics reveal molecular heterogeneity of\nadipose progenitors\nd Proteomic analysis highlights metabolic heterogeneity of\nadipose progenitors\nd PPARg phosphorylation underlies sex differences in iWAT\nAPC differentiation\nd Glutathione metabolism and AhR signaling regulate\nprogenitor cell fate and function\nAuthors\nBo Shan, Clive S. Barker, Mengle Shao,\nQianbin Zhang, Rana K. Gupta,\nYibo Wu\nCorrespondence\nrana.gupta@utsouthwestern.edu\n(R.K.G.),\nwulabproteomics@gmail.com (Y.W.)\nIn brief\nAdipose tissue harbors functionally\ndistinct progenitor cell subpopulations.\nShan et al. utilize multilayered omics to\ndissect adipose progenitor cell\nheterogeneity in three dimensions:\nprogenitor subpopulation, sex, and\nanatomical localization. Functional\nanalysis unveils mechanisms underlying\nsex differences in preadipocyte activation\nand pathways controlling the adipogenic\nand pro-in\ufb02ammatory properties of\ndistinct progenitor subpopulations.\nShan et al., 2022, Cell Metabolism 34, 783\u2013799\nMay 3, 2022 \u00aa 2022 The Authors. Published by Elsevier Inc.\nhttps://doi.org/10.1016/j.cmet.2022.03.012\nll"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 149
encoding: FLOAT32
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{"title": "Supporting Online Material for", "chroma:document": "science.sciencemag.org/content/365/6450/eaaw7317/suppl/DC1 \n \n \n \n \n \n \n \nSupplementary Materials for \n \nConservation, acquisition, and functional impact of sex-biased gene \nexpression in mammals \n \nSahin Naqvi, Alexander K. Godfrey, Jennifer F. Hughes, Mary L. Goodheart,  \nRichard N. Mitchell, David C. Page* \n \n*Corresponding author. Email: dcpage@wi.mit.edu \n \nPublished 19 July 2019, Science 365, eaaw7317 (2019)  \nDOI: 10.1126/science.aaw7317 \n \nThis PDF file includes: \n \nMaterials and Methods \nFigs. S1 to S26 \nTables S3 and S8 \nCaptions for Tables S1, S2, S4 to S7, and S9"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 150
encoding: FLOAT32
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{"title": "Molecular and cellular mechanisms of dopamine-mediated behavioral plasticity in the striatum", "chroma:document": "Molecular and cellular mechanisms of dopamine-mediated behavioral\nplasticity in the striatum\nMilica Cerovic a, Raffaele d\u2019Isa b, Raffaella Tonini c, Riccardo Brambilla b,\u21d1\na School of Biosciences, Cardiff University, CF10 3AX Cardiff, UK\nb Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scienti\ufb01c Institute and University, 20132 Milano, Italy\nc Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy\na r t i c l e\ni n f o\nArticle history:\nAvailable online xxxx\nKeywords:\nStriatum\nNucleus accumbens\nBasal ganglia\nLong-term potentiation\nLong-term depression\nInstrumental learning\nL-DOPA induced dyskinesia\nDrug addiction\nRas\u2013ERK signaling\nEndocannabinoids\na b s t r a c t\nThe striatum is the input structure of the basal ganglia system. By integrating glutamatergic signals from\ncortical and subcortical regions and dopaminergic signals from mesolimbic nuclei the striatum functions\nas an important neural substrate for procedural and motor learning as well as for reward-guided behav-\niors. In addition, striatal activity is signi\ufb01cantly altered in pathological conditions in which either a loss of\ndopamine innervation (Parkinson\u2019s disease) or aberrant dopamine-mediated signaling (drug addiction\nand L-DOPA induced dyskinesia) occurs. Here we discuss cellular mechanisms of striatal synaptic plastic-\nity and aspects of cell signaling underlying striatum-dependent behavior, with a major focus on the neu-\nromodulatory action of the endocannabinoid system and on the role of the Ras\u2013ERK cascade.\n\u0002 2013 Elsevier Inc. All rights reserved.\n1. Introduction\nAmongst brain regions involved in cognitive processing, the\ndorsal striatum and its ventral extension, the nucleus accumbens,\nhave been implicated in a variety of processes in experimental ani-\nmal models, including motor control, instrumental learning and\nhabit formation, reward and drug addiction. Importantly, current\nviews maintain that within the same striatal sub-regions speci\ufb01c"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 151
encoding: FLOAT32
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{"title": "Molecular and cellular mechanisms of dopamine-mediated behavioral plasticity in the striatum", "chroma:document": "signaling cascades may simultaneously control distinct (but possi-\nbly overlapping) gene expression programs resulting from differ-\nent forms of learning, including stimulus\u2013response (S\u2013R) and\ndrug of abuse related behaviors. At the same time, it has become\nclear that a derangement of these molecular mechanisms may oc-\ncur at the striatal level in neurological conditions in which either\ndopamine (DA) is lost, like in Parkinson\u2019s Disease (PD), or made\navailable through pharmacotherapy with the dopamine precursor\nL-DOPA or related dopaminergic agonists whose chronic use al-\nmost invariably result in aberrant adaptations. Considering the\ncentral role of the striatum in the control of movement and some\naspects of cognition it is not surprising that aberrant modulation\nof striatal function is a critical aspect in a number of pathologies\nbesides PD, including L-Dopa induced dyskinesia (LID), Hunting-\nton\u2019s disease (HD), drug abuse, obsessive compulsive disorder, Tou-\nrette\u2019s syndrome and schizophrenia.\nImportantly, synaptic plasticity mechanisms in different re-\ngions of the striatum, including long-term potentiation (LTP) and\ndepression (LTD), as well as depotentiation, are interesting cellular\nmodels of striatal function and dysfunction and may provide a link\nbetween cellular and system events.\nIn this review, we will \ufb01rst describe how normal and patholog-\nical synaptic plasticity occurs in the striatum and then we will fo-\ncus\non\nspeci\ufb01c molecular\nmechanisms\ncontrolling striatum-\ndependent behavior.\n2. Striatal organization and function\nThe striatum is a heterogeneous structure that can be subdi-\nvided at different levels. The major division is in the dorsal and\nventral portions. Dorsal striatum (DS) in primates is composed of\nthe caudate\u2013putamen complex, while in rodents this region is\nfunctionally divided into medial and lateral dorsal striatum. The\nventral part is referred to as nucleus accumbens (NAc) that may\nbe further divided into core and shell. All these sub-regions have"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 152
encoding: FLOAT32
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{"title": "Molecular and cellular mechanisms of dopamine-mediated behavioral plasticity in the striatum", "chroma:document": "similar histological appearance and no sharp anatomical borders\nare present. Thus, their distinct functions may arise from speci\ufb01c\nconnections to different brain structures. From the neurochemical\npoint of view, the NAc receives its major glutamatergic excitatory\n1074-7427/$ - see front matter \u0002 2013 Elsevier Inc. All rights reserved.\nhttp://dx.doi.org/10.1016/j.nlm.2013.06.013\n\u21d1 Corresponding author.\nE-mail address: brambilla.riccardo@hsr.it (R. Brambilla).\nNeurobiology of Learning and Memory xxx (2013) xxx\u2013xxx\nContents lists available at SciVerse ScienceDirect\nNeurobiology of Learning and Memory\njournal homepage: www.elsevier.com/locate/ynlme\nPlease cite this article in press as: Cerovic, M., et al. Molecular and cellular mechanisms of dopamine-mediated behavioral plasticity in the striatum. Neu-\nrobiology of Learning and Memory (2013), http://dx.doi.org/10.1016/j.nlm.2013.06.013"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 153
encoding: FLOAT32
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{"title": "Multi-omics analysis reveals changes in tryptophan and cholesterol metabolism before and after sexual maturation in captive macaques", "chroma:document": "Liu\u00a0et\u00a0al. BMC Genomics          (2023) 24:308  \nhttps://doi.org/10.1186/s12864-023-09404-3\nRESEARCH\nOpen Access\n\u00a9 The Author(s) 2023. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBMC Genomics\nMulti-omics analysis reveals changes \nin\u00a0tryptophan and\u00a0cholesterol metabolism \nbefore\u00a0and\u00a0after sexual maturation in\u00a0captive \nmacaques\nXu Liu1, Xuyuan Liu2, Xinqi Wang2, Ke Shang1, Jiawei Li1, Yue Lan1, Jiao Wang2, Jing Li1, Bisong Yue1,2, \nMiao He3* and Zhenxin Fan1* \nAbstract \nRhesus macaques (Macaca mulatta, RMs) are widely used in sexual maturation studies due to their high genetic and \nphysiological similarity to humans. However, judging sexual maturity in captive RMs based on blood physiological \nindicators, female menstruation, and male ejaculation behavior can be inaccurate. Here, we explored changes \nin RMs before and after sexual maturation based on multi-omics analysis and identified markers for determining"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 154
encoding: FLOAT32
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{"title": "Multi-omics analysis reveals changes in tryptophan and cholesterol metabolism before and after sexual maturation in captive macaques", "chroma:document": "sexual maturity. We found that differentially expressed microbiota, metabolites, and genes before and after sexual \nmaturation showed many potential correlations. Specifically, genes involved in spermatogenesis (TSSK2, HSP90AA1, \nSOX5, SPAG16, and SPATC1) were up-regulated in male macaques, and significant changes in gene (CD36), metabolites \n(cholesterol, 7-ketolithocholic acid, and 12-ketolithocholic acid), and microbiota (Lactobacillus) related to cholesterol \nmetabolism were also found, suggesting the sexually mature males have stronger sperm fertility and cholesterol \nmetabolism compared to sexually immature males. In female macaques, most differences before and after sexual \nmaturity were related to tryptophan metabolism, including changes in IDO1, IDO2, IFNGR2, IL1\u0392, IL10, L-tryptophan, \nkynurenic acid (KA), indole-3-acetic acid (IAA), indoleacetaldehyde, and Bifidobacteria, indicating that sexually mature \nfemales exhibit stronger neuromodulation and intestinal immunity than sexually immature females. Cholesterol \nmetabolism-related changes (CD36, 7-ketolithocholic acid, 12-ketolithocholic acid) were also observed in female and \nmale macaques. Exploring differences before and after sexual maturation through multi-omics, we identified potential \nbiomarkers of sexual maturity in RMs, including Lactobacillus (for males) and Bifidobacterium (for females) valuable for \nRM breeding and sexual maturation research.\nKeywords Rhesus macaques, Sexual maturity, Multi-omics, Gut microbiome, Blood transcriptome and metabolome\n*Correspondence:\nMiao He\nhemiao@ibt.pumc.edu.cn\nZhenxin Fan\nzxfan@scu.edu.cn\nFull list of author information is available at the end of the article"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 155
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{"title": "Neuroimaging studies of striatum in cognition part II: Parkinson's disease", "chroma:document": "REVIEW\npublished: 08 October 2015\ndoi: 10.3389/fnsys.2015.00138\nFrontiers in Systems Neuroscience | www.frontiersin.org\n1\nOctober 2015 | Volume 9 | Article 138\nEdited by:\nLili-Naz Hazrati,\nUniversity of Toronto, Canada\nReviewed by:\nFahad Sultan,\nUniversity T\u00fcbingen, Germany\nKrystal Lynn Parker,\nUniversity of Iowa, USA\nIman Kamali Sarvestani,\nUniversity of Toronto, Canada\n*Correspondence:\nOury Monchi,\nHealth Science Center, Hotchkiss\nBrain Institute, University of Calgary,\nRoom 2915, 3330 Hospital DR NW,\nCalgary T2N 1N4, AB, Canada\noury.monchi@ucalgary.ca\n\u2020These authors have contributed\nequally to this manuscript.\nReceived: 05 May 2015\nAccepted: 22 September 2015\nPublished: 08 October 2015\nCitation:\nHanganu A, Provost J-S and\nMonchi O (2015) Neuroimaging\nstudies of striatum in cognition part II:\nParkinson\u2019s disease.\nFront. Syst. Neurosci. 9:138.\ndoi: 10.3389/fnsys.2015.00138\nNeuroimaging studies of striatum in\ncognition part II: Parkinson\u2019s disease\nAlexandru Hanganu 1, 2, 3 \u2020, Jean-Sebastien Provost 3, 4 and Oury Monchi 1, 2, 3* \u2020\n1 Department of Clinical Neurosciences and Department of Radiology, Cumming School of Medicine, University of Calgary,\nCalgary, AB, Canada, 2 Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, 3 Centre de Recherche de\nl\u2019Institut Universitaire de G\u00e9riatrie de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC, Canada, 4 Department of Psychology,\nFaculty of Arts and Sciences, University of Montreal, Montreal, QC, Canada\nIn recent years a gradual shift in the de\ufb01nition of Parkinson\u2019s disease (PD) has\nbeen established, from a classical akinetic-rigid movement disorder to a multi-system\nneurodegenerative disease. While the pathophysiology of PD is complex and goes much\nbeyond the nigro-striatal degeneration, the striatum has been shown to be responsible\nfor many cognitive functions. Patients with PD develop impairments in multiple cognitive\ndomains and the PD model is probably the most extensively studied regarding striatum"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 156
encoding: FLOAT32
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{"title": "Neuroimaging studies of striatum in cognition part II: Parkinson's disease", "chroma:document": "dysfunction and its in\ufb02uence on cognition. Up to 40% of PD patients present cognitive\nimpairment even in the early stages of disease development. Thus, understanding the\nkey patterns of striatum and connecting regions\u2019 in\ufb02uence on cognition will help develop\nmore speci\ufb01c approaches to alleviate cognitive impairment and slow down its decline.\nThis review focuses on the contribution of neuroimaging studies in understanding how\nstriatum impairment affects cognition in PD.\nKeywords: striatum, cognition, Parkinson\u2019s disease, neuroimaging, dopamine\nIntroduction\nParkinson\u2019s disease (PD) is a progressive neurodegenerative disorder that a\ufb00ects up to 2% of\nindividuals aged 65 years and older (Rijk et al., 1997) and has an incidence of 14 per 100,000\nindividuals (Hirtz et al., 2007). In people over 70 years the incidence is much higher\u2014160 per\n100,000 individuals (Hirtz et al., 2007), and a\ufb00ects nearly 10% of people older than 80 years (von\nCampenhausen et al., 2005). Furthermore, the prevalence of PD is expected to double by 2030\n(Dorsey et al., 2007). While PD is associated with a complex pathophysiology that can potentially\na\ufb00ect most of the brain, the motor cardinal symptoms of PD are largely due to degeneration of\ndopamine (DA) neurons in the substantia nigra pars compacta (Albin et al., 1989). This pattern of\nneurodegeneration starts from dorsal striatum and extends to more ventral parts of the striatum as\nthe disease progresses (Kish et al., 1988).\nSince the second part of the 1980\u2019s it is becoming increasingly clear that cognitive de\ufb01cits can\nbe present even at the early stages of PD (Taylor et al., 1986; Taylor and Saint-Cyr, 1995; Dubois\nand Pillon, 1996). Initial investigations in mild to moderately a\ufb00ected PD patients emphasized\nde\ufb01cits in executive functions (e.g., planning and set-shifting), which resemble those found in\npatients with frontal lobe damage (Taylor et al., 1986; Owen et al., 1990, 1992). These are consistent"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 157
encoding: FLOAT32
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{"title": "Neuroimaging studies of striatum in cognition part II: Parkinson's disease", "chroma:document": "with the fronto-striatal dysfunction occurring in PD reported by our group and many others.\nHowever, non-frontal cognitive de\ufb01cits including visuospatial and language function di\ufb03culties\nare also recognized in early-PD patients and at various stages of disease progression. In the context\nof this review we concentrate on the cognitive de\ufb01cits that are most likely to originate from the"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 158
encoding: FLOAT32
metadata:
{"title": "Sexual Dimorphism in Cardiovascular Biomarkers: Clinical and Research Implications", "chroma:document": "Sexual Dimorphism in Cardiovascular Biomarkers: Clinical and \nResearch Implications\nEmily S. Lau, MD, MPH1, Aleksandra Binek, PhD2, Sarah J. Parker, PhD, MS2, Svati H. Shah, \nMD, MS, MHS3, Markella V. Zanni, MD4, Jennifer E Van Eyk, PhD2, Jennifer E. Ho, MD5\n1Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA\n2Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA\n3Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA\n4Metabolism Unit, Division of Endocrinology, Massachusetts General Hospital, Boston, \nMassachusetts, USA\n5Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, \nMassachusetts, USA\nAbstract\nSex-based differences in cardiovascular disease (CVD) presentation, diagnosis, and response \nto therapies are well established, but mechanistic understanding and translation to clinical \napplications are limited. Blood-based biomarkers have become an important tool for interrogating \nbiologic pathways. Understanding sexual dimorphism in the relationship between biomarkers and \nCVD will enhance our insights into CVD pathogenesis in women, with potential to translate \nto improved individualized care for men and women with or at risk for CVD. In this review, \nwe examine how biologic sex associates with differential levels of blood-based biomarkers and \ninfluences the effect of biomarkers on disease outcomes. We further summarize key differences \nin blood-based cardiovascular biomarkers along central biologic pathways, including myocardial \nstretch/injury, inflammation, adipose tissue metabolism, and fibrosis pathways in men vs women. \nFinally, we present recommendations for leveraging our current knowledge of sex differences in \nblood-based biomarkers for future research and clinical innovation.\nKeywords\nBiomarkers; Cardiovascular Disease; Women; Sex; Gender\nINTRODUCTION\nSex-related differences in cardiovascular disease (CVD) risk, pathophysiology, disease"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 159
encoding: FLOAT32
metadata:
{"title": "Sexual Dimorphism in Cardiovascular Biomarkers: Clinical and Research Implications", "chroma:document": "presentation, response to therapy, and prognosis have been well characterized, but \nmechanistic understanding and implications for clinical practice are incompletely \nCorrespondence to: Jennifer E. Ho, MD, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E/CLS 945, Boston, MA \n02215-5491, Phone: 617-735-4102, Fax: 617-735-4207, jho@bidmc.harvard.edu. \nHHS Public Access\nAuthor manuscript\nCirc Res. Author manuscript; available in PMC 2023 February 18.\nPublished in final edited form as:\nCirc Res. 2022 February 18; 130(4): 578\u2013592. doi:10.1161/CIRCRESAHA.121.319916.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 160
encoding: FLOAT32
metadata:
{"title": "Neuroendocrine asymmetry", "chroma:document": "Neuroendocrine Asymmetry\nIda Gerendai and Be\u00b4la Hala\u00b4sz\nNeuroendocrine Research Laboratory, Department of Human Morphology and Developmental\nBiology, Semmelweis University of Medicine, Budapest, Hungary\nThe information available at present clearly indicates that asymmetry exists from the\nlevel of elementary particles to the human cerebral cortex, the latest stage of evolution.\nCerebral lateralization is one of the well-known asymmetries. This paper summarizes\nthe data published in the past decades on the asymmetry of the neuroendocrine system.\nThe information on the sided-differences between the gonads, adrenals, and thyroid lobes\nand that on the lateralization of hypothalamic, limbic, and other brain structures\nparticipating in the control of the endocrine glands as well as relevant clinical observa-\ntions are reviewed here. The innervation of the peripheral endocrine glands is also brie\ufb02y\nsummarized because the afferent and efferent \ufb01bers of these glands may represent one\npart of the pathway involved in neuroendocrine asymmetry. The data reviewed clearly\nindicate that some kind of asymmetry (morphological, biochemical, physiological, patho-\nlogical) is evident at different levels of the neuroendocrine system (at limbic, hypotha-\nlamic, peripheral endocrine glands and their innervation) and there are species, sex, and\nage differences. Most of the information accumulated deals with the CNS\u2013gonadal\nsystem. A majority of the observations suggest that in both male and female rats there is\na predominance of the right half of brain structures controlling gonadal function. The\nasymmetry, however, is not restricted to CNS structures: it also exists at the level of the\ngonads, including their innervation. It appears that the characteristic pattern of the\nCNS\u2013gonadal system becomes \ufb01xed only after sexual maturation. Very few reports are\navailable suggesting some kind of asymmetry of the CNS\u2013adrenal cortex and the\nCNS\u2013thyroid system. There are convincing \ufb01ndings consistent with the view that in"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 161
encoding: FLOAT32
metadata:
{"title": "Neuroendocrine asymmetry", "chroma:document": "addition to the hypothalamo-adenohypophyseal system acting via the general circulation\non the peripheral endocrine glands, there is also a pure neural link between the CNS and\nthe gonads, the CNS and the adrenal gland, and also between the CNS and the thyroid.\nThis link contains afferent and efferent pathways and is able to modulate the functional\nactivity or the responsiveness of the gland. It may also serve as a neural re\ufb02ex arc. It is\nassumed that the neuroendocrine asymmetry expresses itself through (i) hypophysiotro-\nphic neurohormones and hormones of the peripheral endocrine glands, (ii) neural\npathways, or (iii) a combination of (i) and (ii). The authors hope that this publication, in\naddition to providing an overview, will also stimulate research, both basic and clinical, in\nthis exciting area of neuroendocrinology. KEY WORDS: asymmetry; hypothalamus; limbic\nsystem; neuroendocrine; endocrine glands; innervation.\nr 1997 Academic Press\nHISTORICAL INTRODUCTION\nThe \ufb01rst evidence for cerebral asymmetry was provided by Paul Broca in\n1861 (16). He reported that disturbance of language function called aphasia\nAddress correspondence and reprint requests to Be\u00b4la Hala\u00b4sz, Department of Human Morphol-\nogy, Tu\u00a8zolto\u00b4 u.58., H-1094 Budapest, Hungary, Telephone: (36-1) 215-5847, Fax: (36-1) 215-3064.\nFRONTIERS IN NEUROENDOCRINOLOGY 18, 354\u2013381 (1997)\nARTICLE NO. FN970154\n354\n0091-3022/97 $25.00\nCopyright r 1997 by Academic Press\nAll rights of reproduction in any form reserved."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 162
encoding: FLOAT32
metadata:
{"title": "Neurofilament and neural cell adhesion molecule immunocytochemistry of Huntington's disease striatum", "chroma:document": "Newoflament and Neural Cell \nAdhesion Mo1ecul.e Immunocytochemistry \nof Huntington\u2019s Disease Striatum \nKuninobu Nihei, MD, PhD, and Neil W. Kowall, MD \n~ \nWe examined normal and Huntington\u2019s disease (HI)) human striatum with specific monoclonal antibodies to nonphos- \nphorylated (SMI 32) and phosphorylated (SMI 31) neurofilament and neural cell adhesion molecule (NCAM). SMI 32 \nidentifies medium-sized neuronal perikarya and dendrites in normal striatum. Axons are not immunoreactive. In \nhigh-grade HD striatum (grades 3 and 4) SMI 32 neurons are morphologically abnormal and significantly depleted. \nDendritic arbors are intensely immunoreactive, tortuous, and fragmented, especially in the subependymal zone. Prolif- \nerative SMI 32-positive sprout-like structures and axon-like processes are seen. SMI 31 normally stains a fine meshwork \nof axon-like processes that become intensely immunoreactive, condensed, convoluted, and fragmented in HD. NCAM \nstaining is minimal in normal striatum, but, in HD striatum, many dot- and thread-like structures are found, especially \nin the subependymal region. The abnormalities revealed by SMI 31, SMI 32, and NCAM suggest that neurofilament \nphosphorylation is altered and growth related proteins are reexpressed in HD. Dephosphorylation and destabilization \nof the cytoskeleton may contribute to neuronal inlury and death in HD. \nNihei K, Kowall NW. Neurofilament and neural cell adhesion molecule ~mmunocytochemistry of \nHuntington\u2019s disease striatum Ann Neurol 1992,3 1 59-63 \nHuntington\u2019s disease (HD) is a hereditary disorder \ncharacterized pathologically by depletion of specific \nneuronal subsets in the striatum, cortex, and hypothala- \nmus [l-51. Local circuit neurons without spines resist \ndegeneration in the striatum and cortex, whereas spiny \nprojection neurons show early evidence of degenera- \ntion. Graveland and colleagues 161 used a rapid Golgi \nimpregnation procedure to demonstrate a range of \nmorphological changes affecting the dendritic tree of"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 163
encoding: FLOAT32
metadata:
{"title": "Neurofilament and neural cell adhesion molecule immunocytochemistry of Huntington's disease striatum", "chroma:document": "spiny striatal neurons in HD. Dendritic pruning, spine \nloss, and bizarre proliferative changes occur, suggesting \nthat abortive regeneration may occur in tandem with \ndegeneration in HD. Recently, Ferrante and associates \n[ 7) used section-Golgi and calbindin immunocyto- \nchemical methods to identify spiny neurons and to \nshow that proliferative dendritic changes may be an \nearly feature of HD striatum preceding dendritic prun- \ning and neuronal loss. \nThe neuronal cytoskeleton has a critical role in the \ndevelopment and maintenance of neuronal morphol- \nogy. Alterations of neuronal morphology in HD associ- \nated with selective patterns of neuronal degeneration \nmay therefore be associated with specific alterations \nin the neuronal cytoskeleton. Specific cytoskeletal \nchanges may be associated with both degenerative and \nproliferative changes in HD, as has been shown in Alz- \nheimer\u2019s disease (AD) CS, 91. \nIn AD, proliferative dendritic changes occur in con- \njunction with neuronal loss and reorganization of the \nneuronal cytoskeleton 181. As in HD, a subset of pyra- \nmidal projection neurons enriched in neurofilament \nimmunoreactivity degenerates [lo}. Selective loss of \nprojection neurons in AD is associated with sprouting \nof remaining axonal terminals that occupy vacated syn- \naptic sites. This progression is well illustrated by the \nreorganization of synaptic terminals in the molecular \nlayer of the dentate gyms in AD. Selective depletion \nof layer I1 entorhinal stellate neurons that project to \nthe dentate gyrus is associated with proliferation of \nlocal peptidergic and acetylcholinesterase-positive axon \nterminals, along with increased immunoreactivity for \nthe axonal growth-cone marker, neural cell adhesion \nmolecule (NCAM) [ll-141. \nIn this study, we chose specific markers for post- \ntranslational isoforms of \nneurofilament \nand the \ngrowth-cone marker NCAM to examine patterns of \ncytoskeletal protein alteration and axonal proliferation \nin HD striatum. The antibody designated SMI 32 rec-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 164
encoding: FLOAT32
metadata:
{"title": "Neurofilament and neural cell adhesion molecule immunocytochemistry of Huntington's disease striatum", "chroma:document": "ognizes a phosphatase-resistant epitope in the heavy \nand medium neurofilament polypeptides that are pri- \nFrom the Experimental Neuropdrhology Laboratory and Neurology \nService, Massachusetts General Hospital, Boston, MA. \nReceived Mar 18, 1991, and in revised form Jun 5. Accepted for \npublication Jun 7, 1991. \nAddress correspondence to Dr Kowall, Neurology Service, Massa- \nchusetts General Hospital, Boston, MA 02 114. \nCopyright 0 1792 by the American Neurological Association \n59"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 165
encoding: FLOAT32
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{"title": "Developmental mechanisms underlying the evolution of human cortical circuits", "chroma:document": "Developmental mechanisms underlying the evolution of human \ncortical circuits\nPierre Vanderhaeghen1,2,\u2020, Franck Polleux3,4,\u2020\n1VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium\n2Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium\n3Department of Neuroscience, Columbia University Medical Center, New York, NY, USA\n4Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA\nAbstract\nThe brain of modern humans has evolved remarkable computational abilities that enable \nhigher cognitive functions. These capacities are tightly linked to an increase in the size and \nconnectivity of the cerebral cortex, which is thought to have resulted from evolutionary changes \nin the mechanisms of cortical development. Convergent progress in evolutionary genomics, \ndevelopmental biology and neuroscience has recently enabled the identification of genomic \nchanges that act as human-specific modifiers of cortical development. These modifiers influence \nmost aspects of corticogenesis, from the timing and complexity of cortical neurogenesis to \nsynaptogenesis and the assembly of cortical circuits. Mutations of human-specific genetic \nmodifiers of corticogenesis have started to be linked to neurodevelopmental disorders, providing \nevidence for their physiological relevance and suggesting potential relationships between the \nevolution of the human brain and its sensitivity to specific diseases.\nIntroduction\nApproximately 6-8 million years ago, the common ancestor of great apes (chimpanzees \nand bonobos) and species of the homo lineage lived in Africa. Following the divergence \nof hominins, one branch, through multiple radiation (in which new species emerge) and \nextinction events, gave rise to Homo sapiens approximately 300,000 years ago 1. As a \nresult of this evolution, the brain of modern humans displays remarkable cognitive abilities \nthat enable functions such as elaborate working memory, self-awareness, advanced forms"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 166
encoding: FLOAT32
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{"title": "Developmental mechanisms underlying the evolution of human cortical circuits", "chroma:document": "of communication, complex tool making and cultural development 2,3. The mechanisms \nunderlying the evolutionary emergence of human cognitive abilities constitute a long-\nstanding topic of interest in neuroscience that has recently been transformed by the \ncoalescence of major advances in comparative genomics [G], developmental neurobiology \n\u2020 pierre.vanderhaeghen@kuleuven.be; fp2304@columbia.edu.\nAuthor contributions\nThe authors contributed equally to all aspects of the article.\nCompeting interests\nThe authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nNat Rev Neurosci. Author manuscript; available in PMC 2023 May 01.\nPublished in final edited form as:\nNat Rev Neurosci. 2023 April ; 24(4): 213\u2013232. doi:10.1038/s41583-023-00675-z.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 167
encoding: FLOAT32
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{"title": "New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson's disease", "chroma:document": "www.thelancet.com/neurology   Vol 12   August 2013 \n811\nReview\nNew experimental and clinical links between the hippocampus \nand the dopaminergic system in Parkinson\u2019s disease\nPaolo Calabresi, Anna Castrioto, Massimiliano Di Filippo, Barbara Picconi\nParkinson\u2019s disease is a common progressive neurodegenerative disease, of which the main neuropathological \nhallmark is dopaminergic neuronal loss. Increased attention has been directed towards non-motor symptoms in \nParkinson\u2019s disease, such as cognitive impairment and behavioural disorders. Clinical and experimental \ufb01 ndings \nsupport the view that the hippocampus, a temporal lobe structure involved in physiological learning and memory, is \nalso implicated in the cognitive dysfunction seen in some patients with Parkinson\u2019s disease. Moreover, emerging data \nsuggest interactions between the dopaminergic systems and the hippocampus in synaptic plasticity, adaptive memory, \nand motivated behaviour. This structure is also implicated in the pathophysiology of other non-motor symptoms, \nsuch as impulse control disorders, anosmia, and fatigue. Evidence from clinical observations and experimental \nstudies suggest a complex hippocampal cross-talk among the dopaminergic and other transmitter systems. \nFurthermore, neurotrophic factors might interact with the hippocampal dopaminergic system having possible \nimplications on the non-motor symptoms seen in patients with Parkinson\u2019s disease.\nIntroduction\nParkinson\u2019s disease is a common progressive neuro-\ndegenerative disease, of which the main neuropathological \nhallmarks are dopaminergic neuronal loss in the pars \ncompacta of the substantia nigra and accumulation of \nintraneuronal inclusions called Lewy bodies and Lewy \nneurites.1 Clinically, Parkinson\u2019s disease is a motor disorder \ndominated by bradykinesia, rigidity, resting tremor, and \npostural instability that has a good response to \ndopaminergic replacement therapy. However, the classic \nview of Parkinson\u2019s disease as a pure motor and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 168
encoding: FLOAT32
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{"title": "New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson's disease", "chroma:document": "dopaminergic disorder is changing. In the advanced stages \nof Parkinson\u2019s disease, most disability comes from motor \nsymptoms such as axial signs that do not respond to \ndopaminergic therapy, which suggests the involvement of \nsystems other than the dopaminergic. Additionally, a wide \nrange of non-motor symptoms is present in patients with \nParkinson\u2019s disease,2,3 which occur not only in the advanced \nstages, but also in the early phases. Many symptoms, such \nas hyposmia, rapid eye movement sleep behaviour \ndisorder, constipation, depression, anxiety, and apathy, \nmight precede the onset of motor disease.2,3 The \nmechanisms underlying these symptoms are complex, \nand neuropathological and clinical \ufb01 ndings have shown \nthat both the dopaminergic and non-dopaminergic \nsystems, including the brainstem acetylcholine, noradren-\naline, and serotonin systems, are involved.2\u20135 For example, \nLewy body deposition occurs during the early stages in the \ndorsal motor nucleus of the vagus nerve and in the locus \ncoeruleus, and at advanced stages neuronal loss is seen in \nthe cholinergic and serotoninergic brainstem systems.5\nSeveral studies6,7 have shown that apathy in Parkinson\u2019s \ndisease responds to dopaminergic treatment, which \nsuggests that apathy is related to dopaminergic \ndysfunction. Conversely, a serotoninergic change in the \nbasal ganglia and limbic structures  has been related to \nfatigue, another non-motor symptom of Parkinson\u2019s \ndisease.8 Similarly, depression seems to be related not \nonly to dopaminergic dysfunction,9 but also to \nhippocampal serotoninergic dysfunction.10 Moreover, \nemerging data for non-motor symptoms in Parkinson\u2019s \ndisease, such as cognitive impairment and behavioural \ndisorders, support the role of the hippocampus in \ncognitive function and behaviour.11\u201313\nThe hippocampus is a temporal lobe structure \nimplicated in learning and memory processes.14 In the \ntraditional view of Parkinson\u2019s disease, the hippocampus \nwas not considered to have a role, except for its possible"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 169
encoding: FLOAT32
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{"title": "New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson's disease", "chroma:document": "implications in dementia. However, emerging data from \nanimal models15,16 and human studies17\u201319 have altered this \nview and suggest a key role of the interaction between \ndopamine transmission and hippocampal synaptic \nplasticity in memory and behaviour.20\u201322 Any imbalance in \nthis interaction might be implicated in the genesis of not \nonly dementia, but also other neuropsychiatric aspects of \nParkinson\u2019s disease.\nSeveral reviews have discussed the potential association \nof the pathophysiological mechanisms of early mani-\nfestations,23 non-motor symptoms,2 neuropsychiatric \nissues,12,13,24  and dopamine and reward,11 with the interplay \nbetween the hippocampus and the ventral striatum in \nParkinson\u2019s disease.16,21\nIn this Review, we summarise the major \ufb01 ndings from \nclinical observations and experimental studies using \nmodels of Parkinson\u2019s disease that support a crucial \ninteraction between dopaminergic systems and the \nhippocampus, and their involvement in Parkinson\u2019s \ndisease.\nAnatomical and functional links between the \nhippocampus, basal ganglia, and dopaminergic \nsystems\nThe hippocampus is a medial temporal lobe structure \nimplicated in declarative memory (eg, referring to events \nin a speci\ufb01 c place and time).14,25 Recently, in parallel to the \nincreasing insight into neuropsychiatric symptoms in \nParkinson\u2019s disease, it has been hypothesised that \ndopamine and its interactions with the hippocampus \nLancet Neurol 2013; 12: 811\u201321\nClinica Neurologica, Universit\u00e0 \ndegli Studi di Perugia, Ospedale \nS Maria della Misericordia, \nPerugia, Italy \n(Prof P Calabresi MD, \nA Castrioto MD, \nM Di Filippo PhD); Istituto di \nRicovero e Cura a Carattere \nScienti\ufb01 co (IRCCS) Fondazione \nSanta Lucia, Rome, Italy \n(Prof P Calabresi, B Picconi PhD); \nand Movement Disorder Unit, \nDepartment of Psychiatry and \nNeurology, CHU de Grenoble, \nJoseph Fourier University, \nGrenoble, France (A Castrioto)\nCorrespondence to:\nProf Paolo Calabresi, Clinica \nNeurologica, Universit\u00e0 degli \nStudi di Perugia, Ospedale"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 170
encoding: FLOAT32
metadata:
{"title": "New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson's disease", "chroma:document": "S Maria della Misericordia, \n06156 Perugia, Italy\ncalabre@unipg.it"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 171
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{"title": "Therapeutic strategies for COVID-19: progress and lessons learned", "chroma:document": "Nature Reviews Drug Discovery | Volume 22 | June 2023 | 449\u2013475\n449\nnature reviews drug discovery\nhttps://doi.org/10.1038/s41573-023-00672-y\nReview article\n Check for updates\nTherapeutic strategies for COVID-19: \nprogress and lessons learned\nGuangdi Li\u2009\n \u20091 \n, Rolf Hilgenfeld\u2009\n \u20092 \n, Richard Whitley\u2009\n \u20093 \n & Erik De Clercq\u2009\n \u20094 \nAbstract\nThe coronavirus disease 2019 (COVID-19) pandemic has stimulated \ntremendous efforts to develop therapeutic strategies that target \nsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or \nhuman proteins to control viral infection, encompassing hundreds \nof potential drugs and thousands of patients in clinical trials. So far, \na few small-molecule antiviral drugs (nirmatrelvir\u2013ritonavir, remdesivir \nand molnupiravir) and 11 monoclonal antibodies have been marketed \nfor the treatment of COVID-19, mostly requiring administration within \n10 days of symptom onset. In addition, hospitalized patients with \nsevere or critical COVID-19 may benefit from treatment with previously \napproved immunomodulatory drugs, including glucocorticoids \nsuch as dexamethasone, cytokine antagonists such as tocilizumab \nand Janus kinase inhibitors such as baricitinib. Here, we summarize \nprogress with COVID-19 drug discovery, based on accumulated findings \nsince the pandemic began and a comprehensive list of clinical and \npreclinical inhibitors with anti-coronavirus activities. We also discuss \nthe lessons learned from COVID-19 and other infectious diseases with \nregard to drug repurposing strategies, pan-coronavirus drug targets, \nin vitro assays and animal models, and platform trial design for the \ndevelopment of therapeutics to tackle COVID-19, long COVID and \npathogenic coronaviruses in future outbreaks.\nSections\nIntroduction\nViral targets for antiviral \nagents\nHost targets for antiviral \nagents\nTargeting immune and \ninflammatory responses  \nand coagulation\nOutlook and challenges\nConclusions"}


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id: 172
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{"title": "Therapeutic strategies for COVID-19: progress and lessons learned", "chroma:document": "1Xiangya School of Public Health, Central South University; Hunan Children\u2019s Hospital, Changsha, China. \n2Institute of Molecular Medicine & German Center for Infection Research (DZIF), University of L\u00fcbeck, L\u00fcbeck, \nGermany. 3Department of Paediatrics, Microbiology, Medicine and Neurosurgery, University of Alabama \nat Birmingham, Birmingham, AL, USA. 4Department of Microbiology, Immunology and Transplantation, \nRega Institute for Medical Research, KU Leuven, Leuven, Belgium. \n\u2009e-mail: liguangdi.research@gmail.com; \nrolf.hilgenfeld@uni-luebeck.de; rwhitley@uabmc.edu; erik.declercq@kuleuven.be"}


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id: 173
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{"title": "Parkinson's disease in women: Mechanisms underlying sex differences", "chroma:document": "European Journal of Pharmacology 895 (2021) 173862\nAvailable online 12 January 2021\n0014-2999/\u00a9 2021 Elsevier B.V. All rights reserved.\nParkinson\u2019s disease in women: Mechanisms underlying sex differences \nBhupesh Vaidya, Kritika Dhamija, Priyanka Guru, Shyam Sunder Sharma * \nDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, India   \nA R T I C L E  I N F O   \nKeywords: \nParkinson\u2019s disease \nEstrogen replacement therapy \nNeuroendocrine \nTherapeutic strategies \nMolecular \nGenetic \nA B S T R A C T   \nParkinson\u2019s disease is a neurodegenerative disease which is associated with different motor, cognitive and mood- \nrelated problems. Though it has been established that Parkinson\u2019s disease is less prevalent in women in com-\nparison to men, the differences tend to diminish with the advancing age. Different genetic, hormonal, neuro-\nendocrinal and molecular players contribute towards the differences in the Parkinson\u2019s disease pathogenesis. \nFurthermore, data available with respect to the therapeutic management of Parkinson\u2019s disease in females is \nlimited; women often tend to suffer more from the side effects of the currently available drugs. The present \nreview highlights the sex-specific differences which play a role in the manifestation of these symptoms and side \neffects of the currently available therapeutic strategies. We have also discussed the current and upcoming \ntherapeutic strategies which are in the clinical trials such as adenosine 2A (A2A) receptor antagonists, estrogen \nreplacement therapy, \u03b1-synuclein targeting vaccines and antibodies, Botulinum toxin A, Fas-associated factor-1 \n(FAF-1) inhibitors, thiazolidinediones, 5-HT1A receptor agonists, dopamine D1/D5 receptor agonists, Glucagon- \nlike peptide 1 (GLP-1) analogues and certain plant based principles for the treatment of Parkinson\u2019s disease in \nwomen.   \n1. Introduction \nHuman brain exhibits differential gene expression across sex as a"}


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id: 174
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{"title": "Parkinson's disease in women: Mechanisms underlying sex differences", "chroma:document": "result of genetic and environmental factors (Bisaglia and Bubacco, 2020; \nCannon and Greenamyre, 2011). These factors may predispose a \nparticular sex to a variety of diseases and disorders including neurode-\ngenerative diseases like Parkinson\u2019s disease and Alzheimer\u2019s disease \n(Hanamsagar and Bilbo, 2016; Thapak et al., 2020a; Thapak et al., \n2020b; Wang et al., 2020). A whole genome-based gene expression and \nsplicing study in the human post mortem brain samples also illustrated \nthat 2.6% of the genes expressed in the brain show sex-based differential \ngene expression. Additionally, 95% of the genes were observed to show \nsex-biased splicing (Trabzuni et al., 2013). This warrants a need to look \nfor novel strategies which take into account the sex differences to \nimprove currently available therapeutic regimens for the treatment of \nneurodegenerative conditions such as Parkinson\u2019s disease. \nGeneral epidemiological trends in Parkinson\u2019s disease showed an \nincrease in the number of cases, from 2.5 million in 1990 to nearly 7 to \n10 million in 2020. Though age-standardized incidence rates have \nshown no change in the ratio of male to female affected during this time, \nit has been widely reported that males tend to have a higher prevalence \nthan females in Parkinson\u2019s disease (Wooten et al., 2004). However, \nincidence rates among men is comparitevely lower in asian men in \ncomparison to women. Additionally, overall ratio of males to females \naffected with Parkinson\u2019s disease also tends to increase with age (Liu \net al., 2016; Van Den Eeden et al., 2003). Hence, there is a need to look \nat the gender differences more seriously to understand the variation in \nthese prevalence rates (Feigin et al., 2019; Statistics). \nDespite the late-onset and less prevalence, women tend to show a \nhigher mortality ratio of 3.76 in comparison to 2.28 in men suffering \nfrom Parkinson\u2019s disease (Morgan et al., 2014). One of the reasons for \nthis could be the higher life expectancy of women in comparison to men"}


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id: 175
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{"title": "Parkinson's disease in women: Mechanisms underlying sex differences", "chroma:document": "(Elbaz et al., 2002). In addition, women tend to have faster disease \nprogression in comparison to men. A recent multi-centric trial also \nsuggested that women are also less likely to have informal caregiver \nsupport from family and friends making them more vulnerable to have \ninferior quality of life in comparison to men (Cerri et al., 2019; \nDahodwala et al., 2018). Further, it necessitates them to have paid \ncaregivers which are less likely in case of male patients with Parkinson\u2019s \ndisease (Cerri et al., 2019). \nThere is a range of pathophysiological factors reported in the liter-\nature which contribute to the sex differences in Parkinson\u2019s disease but \nthese have mostly been overlooked both at the preclinical and clinical \nstages. A report which analyzed the United States Food and Drug \nAdministration drug withdrawals between 1997 and 2000 showed that 8 \n* Corresponding author. \nE-mail address: sssharma@niper.ac.in (S.S. Sharma).  \nContents lists available at ScienceDirect \nEuropean Journal of Pharmacology \njournal homepage: www.elsevier.com/locate/ejphar \nhttps://doi.org/10.1016/j.ejphar.2021.173862 \nReceived 1 October 2020; Received in revised form 10 December 2020; Accepted 7 January 2021"}


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id: 176
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{"title": "Microsoft Word - Supplementary_figs_Khodursky_101722.docx", "chroma:document": "Supplementary figures for \nSex differences in inter-individual gene expression variability across human tissues \n \nAuthors: \nSamuel Khodursky1, Caroline S. Jiang2, Eric B. Zheng1, Roger Vaughan2, Daniel R. Schrider3, Li Zhao1,* \nAffiliations: \n1Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, \nUSA \n2Department of Biostatistics, The Rockefeller University, New York, NY 10065, USA \n3Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA \nCorrespondence to: lzhao@rockefeller.edu"}


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id: 177
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{"title": "Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo", "chroma:document": "RESEARCH ARTICLE General Interest\nTranscriptional sex and regional differences in paired human atrial and\nventricular cardiac biopsies collected in vivo\nX Jane Synnergren,1 Kristina Vukusic,2 Pierre D\u00f6nnes,3 Marianne Jonsson,2 Anders Lindahl,2\nG\u00f6ran Dellgren,4 Anders Jeppsson,4 and Julia Asp2,5\n1Systems Biology Research Center, School of Bioscience, University of Sk\u00f6vde, Sk\u00f6vde, Sweden; 2Department of Laboratory\nMedicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3SciCross AB,\nSk\u00f6vde, Sweden; 4Department of Cardiothoracic Surgery, Sahlgrenska University Hospital Gothenburg, Sweden and\nDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg,\nGothenburg, Sweden; and 5Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden\nSubmitted 24 April 2019; accepted in \ufb01nal form 23 December 2019\nSynnergren J, Vukusic K, D\u00f6nnes P, Jonsson M, Lindahl A,\nDellgren G, Jeppsson A, Asp J. Transcriptional sex and regional\ndifferences in paired human atrial and ventricular cardiac biopsies col-\nlected in vivo. Physiol Genomics 52: 110\u2013120, 2020. First published\nDecember 23, 2019; doi:10.1152/physiolgenomics.00036.2019.\u2014Tran-\nscriptional studies of the human heart provide insight into physiolog-\nical and pathophysiological mechanisms, essential for understanding\nthe fundamental mechanisms of normal cardiac function and how they\nare altered by disease. To improve the understanding of why men and\nwomen may respond differently to the same therapeutic treatment it is\ncrucial to learn more about sex-speci\ufb01c transcriptional differences. In\nthis study the transcriptome of right atrium and left ventricle was\ncompared across sex and regional location. Paired biopsies from \ufb01ve\nmale and \ufb01ve female patients undergoing aortic valve replacement or\ncoronary artery bypass grafting were included. Gene expression anal-\nysis identi\ufb01ed 620 differentially expressed transcripts in atrial and"}


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id: 178
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{"title": "Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo", "chroma:document": "ventricular tissue in men and 471 differentially expressed transcripts\nin women. In total 339 of these transcripts overlapped across sex but\nnotably, 281 were unique in the male tissue and 162 in the female\ntissue, displaying marked sex differences in the transcriptional ma-\nchinery. The transcriptional activity was signi\ufb01cantly higher in atrias\nthan in ventricles as 70% of the differentially expressed genes were\nupregulated in the atrial tissue. Furthermore, pathway- and functional\nannotation analyses performed on the differentially expressed genes\nshowed enrichment for a more heterogeneous composition of biolog-\nical processes in atrial compared with the ventricular tissue, and a\ndominance of differentially expressed genes associated with infection\ndisease was observed. The results reported here provide increased\ninsights about transcriptional differences between the cardiac atrium\nand ventricle but also reveal transcriptional differences in the human\nheart that can be attributed to sex.\ncardiac tissue; differentially expressed genes; gender; gene expres-\nsion; left ventricle; microarray; right atrium; sex; transcription\nINTRODUCTION\nSex differences affect the manifestation of cardiovascular\ndisease and therapeutic responses. Men are more likely to\nsuffer from occlusive coronary artery disease (CAD) (30) and\nstroke (6). Women exhibit higher incidence of nonobstructive\nCAD and microvascular dysfunction (30). Notably, within the\npatient population suffering from diabetes Type 2 the female\nsex has cardioprotective effects (1). Sex disparities are partic-\nularly prominent when it comes to cellular electrophysiology,\nresting heart rates, and arrhythmia susceptibility (3, 24, 38).\nFemale myocytes are reported to have longer action potential\nand greater susceptibility after depolarizations than male myo-\ncytes (3, 38). Moreover, female sex is a risk factor for the\ndevelopment of torsade de pointes arrhythmias, not only in\ncongenital long QT syndromes, but also in acquired long QT"}


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id: 179
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{"title": "Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo", "chroma:document": "syndromes that can arise as an adverse effect of drug treat-\nments (3, 24, 42). Thus, it is of particular importance to learn\nmore about sex-speci\ufb01c transcriptional differences to under-\nstand why men and women may respond differently to the\nsame therapeutic treatment and hence to improve the develop-\nment of more ef\ufb01cient and safe treatments for cardiovascular\ndiseases (34).\nAlthough animal studies provide important information\nabout cardiovascular disease, animal-based models are not\nequivalent to human. This is re\ufb02ected by the fact that several\napproved drugs have been withdrawn from the market due to\ntoxic effects in humans, although no such side effects were\nobserved in any animal studies (25). However, cardiac tissue of\nhuman origin for studies of molecular mechanisms is hard to\ncome by, and the lack of access to cardiac tissue greatly\nhampers cardiac research of human relevance. Open cardiac\nsurgery procedures provide an opportunity to collect human\ncardiac biopsies. From technical aspects it is easier to collect\nbiopsies from the auricula of the right atrium than from the\nother three chambers of the heart. The right atrium is easily\naccessed after sternotomy and is regularly manipulated when\ncardiopulmonary bypass is established. For studies of heart\nfunction, however, the material from the less accessible left\nventricle may be more relevant since this chamber executes the\ncontractile work for the systemic circulation. Although studies\non gene expression pro\ufb01les from different parts of the human\nheart have been performed (3\u20135, 13, 22, 23), it is still not\nelucidated to what extent the transcriptome of the left ventricle\ncan be represented by the auricula of the right atrium.\nTo reveal pathological, functional, and regulatory mecha-\nnisms in tissues and organs, large-scale transcriptional studies\nare extensively used. The gene expression pattern in a speci\ufb01c\nAddress for reprint requests and other correspondence: J. Synnergren, Univ.\nof Sk\u00f6vde Systems Biology Research Center, Box 408, SE-541 28 Sk\u00f6vde,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 180
encoding: FLOAT32
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{"title": "Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo", "chroma:document": "Sweden (e-mail: jane.synnergren@his.se).\nPhysiol Genomics 52: 110\u2013120, 2020.\nFirst published December 23, 2019; doi:10.1152/physiolgenomics.00036.2019.\n1094-8341/20 Copyright \u00a9 2020 the American Physiological Society\n110\nDownloaded from journals.physiology.org/journal/physiolgenomics (061.050.124.187) on September 26, 2022."}


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id: 181
encoding: FLOAT32
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{"title": "Gold binding blood cells and proteins during chrysotherapy", "chroma:document": "Annals of the Rheumatic Diseases, 1980, 39, 31-36\nGold binding to blood cells and serum proteins\nduring chrysotherapy\nR.\nJ. VAN DE STADT AND B. ABBO-TILSTRA\nFrom the Amsterdam Centre for Rheumatic Diseases, Amsterdam, Holland\nSUMMARY\nThe binding of gold to peripheral erythrocytes and serum protein fractions was studied\nduring chrysotherapy of\n1 to 2 years' duration in 43 patients with rheumatoid arthritis. In 45%\nof the patients more than 10% of the gold was found to be strongly bound to blood cells. 5-15%\nof the metal is bound to non-albumin protein fractions at serum gold concentrations larger than\n2 mg/ml. In contrast to the cellular binding of gold the relative binding of gold to non-albumin\nproteins was inversely proportional to the serum concentrations. Binding to neither blood cells nor\nto non-albumin protein fractions was found to be correlated with clinical parameters.\nGold salts have been used in the treatment of rheu-\nmatoid\narthritis (RA) for more than 40\nyears.\nAlthough chrysotherapy has proved to be fairly\nbeneficial in the management of rheumatoid arth-\nritis, controversy still exists on the optimal dosage\nschedule (Krusius\net\nal.,\n1970;\nFreyberg,\n1972;\nLorber, et al., 1973, 1975; Cats, 1976; Rothermich\net al., 1976; Sharp et al., 1977). Most reports indicate\na\nlack\nof correlation\nbetween\npharmacological\nand clinical parameters, including the occurrence\nof adverse reactions (Krusius et al., 1970; Freyberg,\n1972; Gerber et al., 1972; Mascarenhas et al., 1972;\nRubinstein and Dietz,\n1973; Jessop and Johns,\n1973; Lorber, et al., 1973, 1975; Gottlieb et al.,\n1974; Sharp et al., 1977).\nIn vitro experiments suggest that most of the gold\nin the circulation is bound to albumin (Lawrence,\n1961; McQueen, and Dykes, 1969; Mascarenhas\net at., 1972; Campion et al., 1974; Danpure, 1976;\nWard et al., 1977), whereas a minor fraction seems\nto\nbe bound\nto\nimmunoglobulins,\ncomplement\n(Lorber et al., 1972; Schultz et al., 1973; Ward et\nal.,\n1977), or to low molecular weight materials"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 182
encoding: FLOAT32
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{"title": "Gold binding blood cells and proteins during chrysotherapy", "chroma:document": "(Campion et al., 1974; Ward et al., 1977). Almost\nall of these studies have been performed in vitro.\nIn only one study (Ward et al., 1977) was the gold\ndistribution measured in the blood of patients with\nrheumatoid\narthritis\nreceiving chrysotherapy.\nIn\nthe study presented here the binding of gold to\nerythrocytes and the distribution of gold among the\nAccepted for publication 6 March 1979\nCorrespondence to Dr R. J. van de Stadt, Reuma Revali-\ndatie Centrum, Dr Jan van Breemenstraat Adm. Helfrich-\nstraat, 1056 AB Amsterdam, W. Holland.\nserum proteins was studied in relationship to clinical\nparameters.\nMaterial and methods\nPATIENTS\nForty-two patients comprising 18 men (age range\n22-75 years) and 24 women (age range 22-76 years)\nwith\ndefinite\nor\nclassical\nrheumatoid\narthritis\nlasting for more than 6 months and fulfilling the\ncriteria of the American Rheumatism Association\n(Ropes et al., 1959) were admitted. None of the\npatients\nhad\npreviously\nreceived\nchrysotherapy,\ncorticosteroids, immunosuppressive\ndrugs,\nor D-\npenicillamine. Only medication with nonsteroidal\nanti-inflammatory drugs was allowed simultaneously\nwith the gold therapy. During the trial all patients\nreceived\naurothioglucose\n(20%\noily\nsuspension,\nNoury Pharma, Oss) by intramuscular injections\naccording to the following standard schedule: The\nfirst week 5 mg twice a week, the second week 10 mg\ntwice a week, the third week 20 mg once, after which\nthe dose was increased to 30, 40, and 50 mg a week\nsubsequently in most of the cases. All patients were\nfollowed up for 1 to 2 years in this study.\nCLINICAL TESTING PROCEDURES\nBefore admission\nto\nthe\ntrial and subsequently\nat 3-month intervals a complete physical examination\nwas made of all patients. On each occasion the fol-\nlowing parameters were assessed; number of ARA\ncriteria, subjective judgment of clinician and patient,\npain, morning stiffness, weariness,\ngrip strength,\nwalking time over 10 metres, circumference of large\n31"}


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id: 183
encoding: FLOAT32
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{"title": "Perceptual dysfunction in Parkinson's disease: deficit in sequential and predictive voluntary", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983 ;46:145-151\nPerceptual motor dysfunction in Parkinson's disease:\na deficit in sequential and predictive voluntary\nmovement\nYAAKOV STERN,*t RICHARD MAYEUX,t JEFFREY ROSEN,* JOYCE ILSONt\nFrom the Departments of Psychology, City University of New York* and Neurology, Columbia University\nCollege ofPhysicians and Surgeons, t New York, USA\nSUMMARY\nWe studied the ability of Parkinsonian patients and controls to generate voluntary\nmovements on a tracing task. Subjects were videotaped while tracing designs of increasing\ncomplexity, presented on a vertical, transparent screen. Some designs were presented in a\ndegraded form and subjects filled in their missing sections. Subjects also received a constructional\ntask and a test of general intellectual ability. The quality of errors on the tracing task differed in the\nParkinsonian and control groups. Parkinsonian patients made two distinct types of errors. One\nprobably related to the motor disorders of the disease, but another seemed to be related to a higher\nlevel of control over sequential and predictive movements. The latter correlated with performance\non the constructional and general intellectual tasks. These results suggest that Parkinson's disease\nmay affect basal ganglia structures that are necessary for voluntary movements which require\nsequencing or planning. Clinically this may be observed in perceptual motor tasks since they\nrequire both voluntary movement and sequential organisation of behaviour.\nImpairments in perceptual motor or visuospatial\ntasks are among the most frequently encountered\nabnormalities\nin\nneuropsychological\nstudies\nof\nParkinson's disease.5 Many of these tasks require\nvoluntary movements, so these deficits could reflect\nnothing more than the disordered movement of\nParkinson's disease. Alternatively, this disturbance\nin perceptual motor tasks suggests that there may\nalso be a loss of higher order motor control that is\ndistinct from the characteristic motor disorders of\nParkinson's disease."}


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id: 184
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{"title": "Perceptual dysfunction in Parkinson's disease: deficit in sequential and predictive voluntary", "chroma:document": "Certain deficits on tracking\ntasks in Parkinson's disease can be characterised as\nan inability to generate and sequence predictive\nmovements, that is movements that must be accom-\nplished without external feedback to guide them. For\nexample, Flowers6 demonstrated that while Park-\ninsonian patients could successfully track a target\nmoving on an oscilloscope screen in a regular pattern\nat a sufficiently slow speed, tracking performance\ndegenerated when the target was momentarily re-\nmoved from the screen. This perceptual motor deficit\nAddress\nfor reprint\nrequests:\nDr Mayeux, The Neurological\nInstitute, 710 West 168th Street, New York, New York 10032, USA.\nReceived 8 April 1982 and in revised form 27 September 1982\nAccepted 4 October 1982\nmay be a result of impaired generation of control of\nsequential and predictive voluntary movements.\nTo examine this hypothesis, we tested patients\nwith a simplified version of Flowers' tracking task,6\nand with a constructional task. In addition, general\nintellectual function and the severity of symptoms\nwere assessed. We expected that certain errors in\ntracing would relate to the severity of patients'\nParkinsonism,\nthat\nis\ntremor,\nrigidity\nor\nbradykinesia. However, we anticipated that other\nerrors\nin\ntracing,\nparticularly\nthose demanding\npredictive movement, might be related to perfor-\nmance on the constructional and general intelligence\ntests and not to the severity of the Parkinsonism. This\nwork was presented in part at the 33rd annual\nmeeting of the American Academy of Neurology.'\nMethods\nSubjects\nEighteen patients with Parkinson's disease and 14 healthy,\nelderly adult controls volunteered and gave informed\nconsent. We excluded people with a history or overt signs of\ndementia as defined by the DSM 111.8 Fourteen of the 18\npatients were on levodopa therapy (table 1). All subjects\nwere examined by the same neurologist. For the patients,\nwe used a standardised evaluation form rating 21 signs and\n145"}


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id: 185
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{"title": "Dopaminergic retinal cell loss and visual dysfunction in Parkinson\\220s disease", "chroma:document": "Dopaminergic retinal cell loss and visual dysfunction in \nParkinson\u2019s disease\nIsabel Ortu\u00f1o-Lizar\u00e1n, PhD1, Xavier S\u00e1nchez-S\u00e1ez, MSc1, Pedro Lax, PhD1, Geidy E. \nSerrano, PhD2, Thomas G. Beach, MD, PhD2, Charles H. Adler, MD, PhD3, Nicol\u00e1s Cuenca, \nPhD1,4\n1Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain\n2Banner Sun Health Research Institute, Sun City, AZ, USA\n3Mayo Clinic Arizona, Scottsdale, AZ, USA\n4Institute Ram\u00f3n Margalef, University of Alicante, Alicante, Spain\nAbstract\nObjective:\u00a0Considering the demonstrated implication of the retina in PD pathology and the \nimportance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic \namacrine cells and some of their main post-synaptic neurons in the retina of PD.\nMethods:\u00a0Using immunohistochemistry and confocal microscopy, we evaluated morphology, \nnumber, and synaptic connections of dopaminergic cells and their post-synaptic cells, AII \namacrine and melanopsin-containing retinal ganglion cells, in control and PD eyes from human \ndonors.\nResults:\u00a0In PD, dopaminergic amacrine cell number was reduced between a 58% and a 26% in \ndifferent retinal regions, involving a decline in the number of synaptic contacts with AII amacrine \ncells (by 60%) and melanopsin cells (by 35%). Despite losing their main synaptic input, AII cells \nwere not reduced in number, but they showed cellular alterations compromising their adequate \nfunction: i) a loss of mitochondria inside their lobular appendages, that may indicate an energetic \nfailure and ii) a loss of connexin 36, suggesting alterations in the AII coupling and in visual signal \ntransmission from the rod pathway.\nInterpretation:\u00a0The dopaminergic system impairment and the affection of the rod pathway \nthrough the AII cells may explain and be partially responsible for the reduced contrast sensitivity \nor electroretinographic response described in PD. Also, dopamine reduction and the loss of"}


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{"title": "Dopaminergic retinal cell loss and visual dysfunction in Parkinson\\220s disease", "chroma:document": "synaptic contacts with melanopsin cells may contribute to the melanopsin retinal ganglion cell \nloss previously described and to the disturbances in circadian rhythm and sleep reported in PD \npatients. These data support the idea that the retina reproduces brain neurodegeneration and is \nhighly involved in PD pathology.\nCorresponding author: Nicol\u00e1s Cuenca, cuenca@ua.es.\nAuthor Contributions: IOL, PL, GS, TB, CA and NC contributed to the study conception and design. Data collection was performed \nby IOL, XSS, GS and analysis and interpretation by IOL, XSS, PL, GS, TB, CA, and NC. IOL wrote the first draft of the manuscript \nand all authors made comments on previous versions. All authors read and approved the final version.\nPotential Conflicts of Interest: The authors declare that they have no conflict of interest.\nHHS Public Access\nAuthor manuscript\nAnn Neurol. Author manuscript; available in PMC 2023 March 10.\nPublished in final edited form as:\nAnn Neurol. 2020 November ; 88(5): 893\u2013906. doi:10.1002/ana.25897.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 187
encoding: FLOAT32
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{"title": "Brain gene therapy with Trojan horse lipid nanoparticles", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 188
encoding: FLOAT32
metadata:
{"title": "Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infect\\\rion", "chroma:document": "Stabilized HIV-1 envelope immunization induces neutralizing \nantibodies to the CD4bs and protects macaques against \nmucosal infection\nKevin O. Saunders1,2,3,4,*, Robert J. Edwards1,5,\u2020, Kedamawit Tilahun1,5,\u2020, Kartik Manne1,5,\u2020, \nXiaozhi Lu1,5, Derek W. Cain1,5, Kevin Wiehe1,5, Wilton B. Williams1,2,4, Katayoun \nMansouri1,5, Giovanna E. Hernandez1,5, Laura Sutherland1,5, Richard Scearce1,5, Robert \nParks1,5, Maggie Barr1,5, Todd DeMarco1,5, Chloe M. Eater1,5, Amanda Eaton1,2, \nGeorgeanna Morton6, Benjamin Mildenberg6, Yunfei Wang1,5, R. Wes Rountree1,5, Mark A. \nTomai7, Christopher B. Fox8, M. Anthony Moody1,9, S. Munir Alam1,5, Sampa Santra6, Mark \nG. Lewis10, Thomas N. Denny1,5, George M. Shaw11, David C. Montefiori1,2, Priyamvada \nAcharya1,2,*, Barton F. Haynes1,4,5,*\n1Duke Human Vaccine Institute, Duke University Medical Center; Durham, NC 27710.\n2Department of Surgery, Duke University Medical Center; Durham, NC 27710.\n3Department of Microbiology and Molecular Genetics, Duke University Medical Center; Durham, \nNC 27710.\n4Department of Immunology, Duke University Medical Center; Durham, NC, 27710, USA.\n5Department of Medicine, Duke University Medical Center; Durham, NC, 27710, USA.\n6Beth Israel Deaconess Medical Center; Boston, MA, 02215, USA.\n73M Corporate Research Materials Lab, 3M Company; St. Paul, MN, 55144, USA.\n8Infectious Disease Research Institute; Seattle, WA, 98102, USA.\n*Corresponding author: Priyamvada.acharya@duke.edu, Kevin.saunders@duke.edu, Barton.haynes@dm.duke.edu.\n\u2020Contributed equally\nAuthor contributions:\nKOS, GMS, BFH conceptualized and designed the study. XL, KT, DWC, MAM, and KOS isolated, sequenced, produced, and \ncharacterized binding activity of mAbs. K Manne, RJE, K Mansouri, and PA performed electron microscopy experiments. DCM and \nAE performed HIV-1 neutralization assays. WBW and KW performed next-generation sequencing and antibody sequence analysis. \nRP, MB, and BFH performed serum binding and blocking assays and analyzed data. GEH and CME expressed virus antigens and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 189
encoding: FLOAT32
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{"title": "Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infect\\\rion", "chroma:document": "performed antibody binding assays. SMA performed binding assays with recombinant trimers. MGL, LS, RS, SS, GM and BM \nperformed macaque procedures. TD and TND performed viral load PCR experiments. MAT and CBF produced adjuvants for the \nmacaque immunization study. GMS generated challenge stocks. MGL, BFH, KOS, and GMS analyzed challenge data. YW and RWR \nperformed statistical analyses. KOS, RJE, PA, and BFH wrote the original draft of the manuscript, which was edited by all authors.\nSupplementary Materials\nMaterials and Methods \nFig. S1 to S19\nTable S1 to S4\nMDAR Reproducibility Checklist \nData File S1 \nCompeting interests: IDRI has filed patents on emulsion and Alum formulations of 3M-052 and GLA on which CBF is an inventor. \nCBF is also on the scientific advisory board of Maxvax. MAT is an employee of 3M Company. 3M company had no role in the \nexecution of the study, data collection, or data interpretation. BFH and KOS have filed patents regarding the use of CH505 TF \nchTrimer as an immunogen (PCT / US2017 / 020249). All other authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nSci Transl Med. Author manuscript; available in PMC 2023 March 23.\nPublished in final edited form as:\nSci Transl Med. 2022 September 07; 14(661): eabo5598. doi:10.1126/scitranslmed.abo5598.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 190
encoding: FLOAT32
metadata:
{"title": "Rapid plasticity of higher-order thalamocortical inputs during sensory learning", "chroma:document": "Rapid plasticity of higher-order thalamocortical inputs during \nsensory learning\nNicholas J. Audette1,2, Sarah M. Bernhard1, Ajit Ray1, Luke T. Stewart1, Alison L. \nBarth1,2,3,*\n1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, 15213, USA\n2Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, 15213, USA\n3Lead Contact\nAbstract\nNeocortical circuits are sensitive to experience, showing both anatomical and electrophysiological \nchanges in response to altered sensory input. We examined input- and cell-type specific changes \nin thalamo- and intracortical pathways during learning using an automated, home-cage sensory \nassociation training (SAT) paradigm coupling multi-whisker stimulation to a water reward. \nWe found that POm, but not VPM, drives increased cortical activity after 24 hours of SAT, \nwhen behavioral evidence of learning first emerges. Synaptic strengthening within the POm \nthalamocortical pathway was first observed at thalamic inputs to L5 and was not generated by \nsensory stimulation alone. Synaptic changes in L2 were delayed relative to L5, requiring 48 hours \nof SAT to drive synaptic plasticity at thalamic and intracortical inputs onto L2 Pyr neurons. These \ndata identify the POm thalamocortical circuit as a site of rapid synaptic plasticity during learning \nand suggest a temporal sequence to learning-evoked synaptic changes in the sensory cortex.\nIntroduction\nExperience-dependent plasticity is a cardinal feature of the neocortex. Abundant evidence \nindicates that motor or perceptual learning drives changes in neocortical circuits, with \nchanges observed in fMRI signals (Shibata et al., 2016; Summerfield et al., 2006), altered \ntopographic organization (retino-, tono- or somatotopy; (Harris et al., 2001; Kilgard, 1998; \nSchwartz et al., 2002)), enhanced feature-selective responses and increased spike output to \npreviously undetectable stimuli (Glazewski and Barth, 2015; Karni and Sagi, 1991), and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 191
encoding: FLOAT32
metadata:
{"title": "Rapid plasticity of higher-order thalamocortical inputs during sensory learning", "chroma:document": "increased synaptic strength (Cheetham et al., 2008; Clem, 2010; Rioult-Pedotti et al., 2000).\nHow is learning associated with plasticity in specific neocortical circuits? In rodent \nsomatosensory cortex, experience-dependent changes are concentrated in infra- and \n*Correspondence: albarth@andrew.cmu.edu.\nAuthor Contributions\nConceptualization, N.J.A. and A.L.B.; Methodology, N.J.A., S.M. B., A.L.B.; Software, S.M.B.; Formal Analysis, N.J.A.; \nInvestigation, N.J.A., L.T.S., A.R.; Writing \u2013 Original Draft, N.J.A., A.L.B.; Writing \u2013 Reviewing & Editing, N.J.A., S.B., L.T.S., \nA.R., A.L.B.; Visualization, N.J.A.; Supervision, A.L.B.; Funding Acquisition, N.J.A., A.R., A.L.B.\nDeclaration of Interests\nThe authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nNeuron. Author manuscript; available in PMC 2023 March 24.\nPublished in final edited form as:\nNeuron. 2019 July 17; 103(2): 277\u2013291.e4. doi:10.1016/j.neuron.2019.04.037.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 192
encoding: FLOAT32
metadata:
{"title": "Immunogenomics of killer cell Ig-like receptor \\(KIR\\) and HLA class I: Co-evolution and consequences for human health", "chroma:document": "Immunogenomics of killer cell Ig-like receptor (KIR) and HLA \nclass I: Co-evolution and consequences for human health\nNicholas R. Pollock, BSc,\nGenelle F. Harrison, PhD,\nPaul J. Norman, PhD\nDivision of Biomedical Informatics and Personalized Medicine and Department of Immunology \nand Microbiology. Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.\nAbstract\nInteractions of killer cell immunoglobin-like receptors (KIR) with human leukocyte antigens \n(HLA) class I regulate effector functions of key cytotoxic cells of innate and adaptive immunity. \nThe extreme diversity of this interaction is genetically determined, having evolved in the \never-changing environment of pathogen exposure. Diversity of KIR and HLA genes is further \nfacilitated by their independent segregation on separate chromosomes. That fetal implantation \nrelies on many of the same types of immune cells as infection control, places certain constraints \non the evolution of KIR interactions with HLA. Consequently, specific inherited combinations \nof receptors and ligands may predispose to specific immune mediated diseases, including \nautoimmunity. Combinatorial diversity of KIR and HLA class I can also differentiate success \nrates of immunotherapy directed to these diseases. Progress towards both etiopathology and \npredicting response to therapy is being achieved through detailed characterization of the extent \nand consequences of the combinatorial diversity of KIR and HLA. Achieving these goals is \nmore tractable with the development of integrated analyses of molecular evolution, function and \npathology that will establish guidelines for understanding and managing risks. Here we present \nwhat is known about the co-evolution of KIR with HLA class I and the impact of their complexity \non immune function and homeostasis.\nKeywords\nkiller cell Ig-like receptors (KIR); human leucocyte antigen (HLA); natural killer (NK) cells; \ninnate immunity; reproduction; autoimmunity"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 193
encoding: FLOAT32
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{"title": "Immunogenomics of killer cell Ig-like receptor \\(KIR\\) and HLA class I: Co-evolution and consequences for human health", "chroma:document": "The ability of the immune system to distinguish healthy from unhealthy cells is critical for \nthe effective control of pathogens and aberrant cell growth. The system must also diversify \nto survive in the face of emerging and evolving challenges. Killer cell immunoglobin-like \nreceptor (KIR) interactions with their cognate ligands, human leukocyte antigen (HLA) class \nCorresponding Author: Paul J. Norman, Division of Biomedical Informatics and Personalized Medicine, Building 500, Anschutz \nMedical Campus, Aurora, CO 80045, USA. paul.norman@cuanschutz.edu Tel: 303-724-4481. \nCompeting Interests\nThe authors declare no financial or other conflict of interest that could impact this work.\nHHS Public Access\nAuthor manuscript\nJ Allergy Clin Immunol Pract. Author manuscript; available in PMC 2023 March 25.\nPublished in final edited form as:\nJ Allergy Clin Immunol Pract. 2022 July ; 10(7): 1763\u20131775. doi:10.1016/j.jaip.2022.04.036.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 194
encoding: FLOAT32
metadata:
{"title": "Decussating Axons Segregate within the Anterior Core of the Primate Optic Chiasm", "chroma:document": "Decussating Axons Segregate within the Anterior Core of the \nPrimate Optic Chiasm\nJonathan C. Horton,\nMikayla D. Dilbeck,\nJohn R. Economides\nProgram in Neuroscience, Department of Ophthalmology, University of California, San Francisco, \nSan Francisco, CA 94143 USA\nAbstract\nBackground\u2014The axons of ganglion cells in the nasal retina decussate at the optic chiasm. It \nis unclear why tumours cause more injury to crossing nasal fibres, thereby giving rise to temporal \nvisual field loss in each eye. To address this issue, the course of fibres through the optic chiasm \nwas examined following injection of a different fluorescent tracer into each eye of a monkey.\nMethods\u2014Under general anaesthesia, cholera toxin subunit B -- Alexa Fluor 488 was injected \ninto the right eye and cholera toxin subunit B -- Alexa Fluor 594 was injected into the left eye of \na single normal adult male rhesus monkey. After a week\u2019s survival for anterograde transport, serial \ncoronal sections through the primary optic pathway were examined.\nResults\u2014Crossing fibres were confined mainly to a core zone within the anterior and mid \nportions of the optic chiasm. This zone of decussation was delineated by segregated, interwoven \nsheets of green (right eye) and red (left eye) fibres. It expanded steadily to fill more of the optic \nchiasm as fibres coursed posteriorly towards the optic tracts. Eventually, crossed fibres became \ncompletely intermingled with uncrossed fibres, so that ocular separation was lost.\nConclusions\u2014Crossing fibres are concentrated primarily within a distinct, central compartment \nlocated within the anterior two thirds of the optic chiasm. Sellar tumours focus their compressive \nforce on this portion of the structure, explaining why they so often produce visual field loss in the \ntemporal fields.\nCorresponding author: Jonathan C. Horton MD, PhD, University of California, San Francisco, Jonathan.Horton@ucsf.edu, 10 Koret \nWay, San Francisco, CA 94143-0730, Phone: 650-288-8736."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 195
encoding: FLOAT32
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{"title": "Decussating Axons Segregate within the Anterior Core of the Primate Optic Chiasm", "chroma:document": "Contributorship Statement: All 3 authors participated in the experiment, analysis of the data, and authorship of the manuscript.\n1The contents of this article were in part presented at a Festschrift in celebration of the career of Dr. Gordon Plant on this \nretirement. The event took place in March 2021 and was hosted by the Royal Society of Medicine and the United Kingdom \nNeuro-Ophthalmology Society. A video recording of the entire event is available at http://uknos.com.\nCompeting interests None Declared.\nPatient consent for publication Not required.\nEthics Approval UCSF Institutional Animal Care and Use Committee Approval Number AN194334-01C. UCSF Human Research \nProtection Program Institutional Review Board: Exemption.\nHHS Public Access\nAuthor manuscript\nBr J Ophthalmol. Author manuscript; available in PMC 2023 April 01.\nPublished in final edited form as:\nBr J Ophthalmol. 2023 April ; 107(4): 447\u2013452. doi:10.1136/bjo-2022-322235.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 196
encoding: FLOAT32
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{"title": "Pathogenesis of allergic diseases and implications for therapeutic interventions", "chroma:document": "REVIEW ARTICLE\nOPEN\nPathogenesis of allergic diseases and implications for\ntherapeutic interventions\nJi Wang1, Yumei Zhou1, Honglei Zhang1, Linhan Hu1, Juntong Liu1, Lei Wang2, Tianyi Wang1, Haiyun Zhang1, Linpeng Cong1 and\nQi Wang1\u2709\nAllergic diseases such as allergic rhinitis (AR), allergic asthma (AAS), atopic dermatitis (AD), food allergy (FA), and eczema are\nsystemic diseases caused by an impaired immune system. Accompanied by high recurrence rates, the steadily rising incidence rates\nof these diseases are attracting increasing attention. The pathogenesis of allergic diseases is complex and involves many factors,\nincluding maternal-fetal environment, living environment, genetics, epigenetics, and the body\u2019s immune status. The pathogenesis\nof allergic diseases exhibits a marked heterogeneity, with phenotype and endotype de\ufb01ning visible features and associated\nmolecular mechanisms, respectively. With the rapid development of immunology, molecular biology, and biotechnology, many\nnew biological drugs have been designed for the treatment of allergic diseases, including anti-immunoglobulin E (IgE), anti-\ninterleukin (IL)-5, and anti-thymic stromal lymphopoietin (TSLP)/IL-4, to control symptoms. For doctors and scientists, it is becoming\nmore and more important to understand the in\ufb02uencing factors, pathogenesis, and treatment progress of allergic diseases. This\nreview aimed to assess the epidemiology, pathogenesis, and therapeutic interventions of allergic diseases, including AR, AAS, AD,\nand FA. We hope to help doctors and scientists understand allergic diseases systematically.\nSignal Transduction and Targeted Therapy  (2023) 8:138 \n; https://doi.org/10.1038/s41392-023-01344-4\nINTRODUCTION\nAllergic diseases are systemic disorders caused by an impaired\nimmune system. Different allergic diseases, including AR, AAS, AD,\nFA and eczema, are caused by complex interactions between\ngenetic and environmental factors. Allergic diseases are listed by\nthe World Health Organization (WHO) as one of the top three"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 197
encoding: FLOAT32
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{"title": "Pathogenesis of allergic diseases and implications for therapeutic interventions", "chroma:document": "disorders to be prevented and controlled in the 21st century. An\nallergic disease, whilst a systemic disease, can also manifest as\ndifferent local maladies, all of which may lead to anaphylactic\nshock in severe cases. The incidence of allergic diseases is high,\nbringing much suffering to patients. It is estimated that nearly\n500 million and 300 million individuals worldwide have AR and\nAAS, respectively,1 with an increasing number of cases. For AAS,\nmortality rates in women and men are 90 and 170 per million\nindividuals, respectively. About 96% of asthma deaths occur in\nlow-and-middle-income countries.2 It is currently estimated that\nFA affects 1\u201310% of the total population.3 The global prevalence\nrate of AD is 8%,4,5 with a lifetime prevalence reaching 20%.6 In\n2019, there were 171.17 million patients worldwide with AD.7\nDue to the different sites of allergic diseases, the clinical and\npathological manifestations also differ. In AR, after stimulation by\nallergens, including airborne dust mites associated with fecal\nparticles, cockroach remains, pet dander, molds and pollens,\nin\ufb02ammatory cells such as mast cells, CD4+ T cells, B cells,\nmacrophages and eosinophils in\ufb01ltrate the lining of the nasal\ncavity, with in\ufb01ltration into the nasal mucosa. T helper 2 (Th2) cells\npromote the release of immunoglobulin and cytokines, including\ninterleukin (IL)-3, IL-4, IL-5, and IL-13; meanwhile, IgE is also\nproduced by plasma cells. There is, however, still some uncertainty\naround the source of IgE production. Follicular helper T (Tfh) cells\nare a subpopulation of CD4+ T-effector cells, and in recent years it\nhas been discovered that the key cells regulating IgE production\nare not Th2 cells, but Tfh cells. Allergens cross-link IgE that interact\nwith mast cells, which further induces the release of multiple\nmediators\n(including\nhistamine\nand\nleukotrienes),\npromotes\narteriole dilation and vascular permeability, and causes pruritus,\nrunny nose, mucus secretion, and pulmonary smooth muscle"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 198
encoding: FLOAT32
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{"title": "Pathogenesis of allergic diseases and implications for therapeutic interventions", "chroma:document": "contraction.8 Over the next 4\u20138 hours, the released mediators and\ncytokines induce subsequent cellular in\ufb02ammatory reactions (late\nin\ufb02ammatory response), leading to the recurrence of symptoms,\noften nasal congestion, which generally persist.8,9 The immuno-\npathological pro\ufb01les of AR and AAS are very similar in terms of\neosinophil, mast cell and Th2 cell in\ufb01ltration. Although structural\nchanges in airway remodeling are well characterized in AAS, they\nmay also occur in AR. There are also pathophysiological differences\nbetween AR and AAS. In the AAS disease, mucosal pathological\nalterations comprise epithelial hyperplasia, goblet cell metaplasia\nand increased mucus generation. In the submucosal layer, smooth\nmuscle hypertrophy, collagen accumulation and large mucus\nglands prevail, leading to airway narrowing and enhanced mucus\ngeneration during an asthma attack,10 with symptoms such as\ndif\ufb01culty breathing, wheezing, chest pain, and coughing.11 The\npathogenesis of AD is mainly re\ufb02ected by a complex interplay\nbetween epidermal barrier dysfunction, abnormal skin microbiota\nand\ndysregulated\ntype\n2\nT\ncell\nimmunity.12,13\nThe\nabove\npathogenesis induces a series of pathological manifestations such\nReceived: 2 September 2022 Revised: 20 January 2023 Accepted: 3 February 2023\n1National Institute of TCM constitution and Preventive Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China and 2National\nCancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 1000210, China\nCorrespondence: Qi Wang (wangqi710@126.com)\nThese authors contributed equally: Ji Wang, Yumei Zhou\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 199
encoding: FLOAT32
metadata:
{"title": "Spared Premotor Areas Undergo Rapid Nonlinear Changes in Functional Organization Following a Focal Ischemic Infarct in Primary Motor Cortex of Squirrel Monkeys", "chroma:document": "Neurobiology of Disease\nSpared Premotor Areas Undergo Rapid Nonlinear Changes\nin Functional Organization Following a Focal Ischemic\nInfarct in Primary Motor Cortex of Squirrel Monkeys\nErik J. Plautz,1,2\nScott Barbay,1,2 Shawn B. Frost,1,2 Ann M. Stowe,1 Numa Dancause,1 Elena V. Zoubina,1,2\nInes Eisner-Janowicz,1 David J. Guggenmos,1 and Randolph J. Nudo1,2\n1Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160 and 2Landon Center on\nAging, University of Kansas Medical Center, Kansas City, Kansas 66160\nRecovery of motor function after stroke is accompanied by reorganization of movement representations in spared cortical\nmotor regions. It is widely assumed that map reorganization parallels recovery, suggesting a causal relationship. We exam-\nined this assumption by measuring changes in motor representations in eight male and six female squirrel monkeys in the\nfirst few weeks after injury, a time when motor recovery is most rapid. Maps of movement representations were derived\nusing intracortical microstimulation techniques in primary motor cortex (M1), ventral premotor cortex (PMv), and dorsal\npremotor cortex (PMd) in 14 adult squirrel monkeys before and after a focal infarct in the M1 distal forelimb area. Maps\nwere derived at baseline and at either 2 (n = 7) or 3 weeks (n = 7) postinfarct. In PMv the forelimb maps remained\nunchanged at 2 weeks but contracted significantly (242.4%) at 3 weeks. In PMd the forelimb maps expanded significantly\n(1110.6%) at 2 weeks but contracted significantly (257.4%) at 3 weeks. Motor deficits were equivalent at both time points.\nThese results highlight two features of plasticity after M1 lesions. First, significant contraction of distal forelimb motor maps\nin both PMv and PMd is evident by 3 weeks. Second, an unpredictable nonlinear pattern of reorganization occurs in the dis-\ntal forelimb representation in PMd, first expanding at 2 weeks, and then contracting at 3 weeks postinjury. Together with"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 200
encoding: FLOAT32
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{"title": "Spared Premotor Areas Undergo Rapid Nonlinear Changes in Functional Organization Following a Focal Ischemic Infarct in Primary Motor Cortex of Squirrel Monkeys", "chroma:document": "previous results demonstrating reliable map expansions in PMv several weeks to months after M1 injury, the subacute time\nperiod may represent a critical window for the timing of therapeutic interventions.\nKey words: cortical plasticity; ICMS; motor maps; premotor cortex; recovery of function; stroke\nSignificance Statement\nThe relationship between motor recovery and motor map reorganization after cortical injury has rarely been examined in\nacute/subacute periods. In nonhuman primates, premotor maps were examined at 2 and 3 weeks after injury to primary\nmotor cortex. Although maps are known to expand late after injury, the present study demonstrates early map expansion at\n2 weeks (dorsal premotor cortex) followed by contraction at 3 weeks (dorsal and ventral premotor cortex). This nonlinear\nmap reorganization during a time of gradual behavioral recovery suggests that the relationship between map plasticity and\nmotor recovery is much more complex than previously thought. It also suggests that rehabilitative motor training may have\nits most potent effects during this early dynamic phase of map reorganization.\nIntroduction\nStroke remains one of the major causes of death and disability\nworldwide (Gorelick, 2019). Although advances have been made\nin acute stroke therapy, interventions generally are limited to a\nfew hours following stroke (Hollist et al., 2021). Delays in treat-\nment often result in chronic motor impairments requiring inten-\nsive physical rehabilitation and restorative therapies to improve\nfunction. Animal models remain useful for addressing underly-\ning mechanisms of recovery and offer therapeutic targets to de-\nvelop or refine current rehabilitative therapies (Bundy and\nNudo, 2019). Principally, a large effort has been made to under-\nstand the capacity of the brain to reorganize after an ischemic\nReceived July 23, 2022; revised Jan. 10, 2023; accepted Jan. 13, 2023.\nAuthor contributions: E.J.P. and R.J.N. designed research; E.J.P., S.B., S.B.F., A.M.S., N.D., E.V.Z., I.E.-J., and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 201
encoding: FLOAT32
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{"title": "Spared Premotor Areas Undergo Rapid Nonlinear Changes in Functional Organization Following a Focal Ischemic Infarct in Primary Motor Cortex of Squirrel Monkeys", "chroma:document": "D.J.G. performed research; E.J.P. and S.B. analyzed data; and E.P., S.B., and R.J.N. wrote the paper.\nThis work was supported by National Institues of Health Grants U54 NS048126, NIH R01 NS30853, and P30\nHD002528 and Northstar Neuroscience. We thank Bob Cross, Caleb Dunham, Erica Hoover, Diane Larson, and\nPhuong Nguyen for technical assistance and Scott Bury, Pei-chun Fang, David McNeal, Michael Taylor, and Ed\nUrban for assistance with collection of mapping data.\nThe authors declare no competing financial interests.\nCorrespondence should be sent to Randolph J. Nudo at rnudo@kumc.edu or Erik Plautz at\nerik.plautz@utsouthwestern.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1452-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, March 15, 2023 \u2022 43(11):2021\u20132032 \u2022 2021"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 202
encoding: FLOAT32
metadata:
{"title": "Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis", "chroma:document": "Vol.:(0123456789)\n1 3\nInflammopharmacology (2023) 31:1167\u20131182 \nhttps://doi.org/10.1007/s10787-023-01193-1\nREVIEW\nIn\ufb02ammopharmacology\nThalidomide interaction with\u00a0inflammation in\u00a0idiopathic pulmonary \nfibrosis\nNikitha\u00a0Naomi\u00a0Dsouza1\u00a0\u00b7 Varun\u00a0Alampady1\u00a0\u00b7 Krishnaprasad\u00a0Baby1\u00a0\u00b7 Swastika\u00a0Maity1\u00a0\u00b7 Bharath\u00a0Harohalli\u00a0Byregowda1\u00a0\u00b7 \nYogendra\u00a0Nayak1 \nReceived: 10 November 2022 / Accepted: 4 March 2023 / Published online: 25 March 2023 \n\u00a9 The Author(s) 2023\nAbstract\nThe \u201cThalidomide tragedy\u201d is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there \nis a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, \nlepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing tha-\nlidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, \nand selected articles were reviewed. The content includes the proven mechanisms of action of thalidomide relevant to IPF. \nInflammation, oxidative stress, and epigenetic mechanisms are major pathogenic factors in IPF. Transforming growth factor-\u03b2 \n(TGF-\u03b2) is the major biomarker of IPF. Thalidomide is an effective anti-inflammatory drug in inhibiting TGF-\u03b2, interleu-\nkins (IL-6 and IL-1\u03b2), and tumour necrosis factor-\u03b1 (TNF-\u03b1). Thalidomide binds cereblon, a process that is involved in the \nproposed mechanism in specific cancers such as breast cancer, colon cancer, multiple myeloma, and lung cancer. Cereblon \nis involved in activating AMP-activated protein kinase (AMPK)-TGF-\u03b2/Smad signalling, thereby attenuating fibrosis. The \npast few years have witnessed an improvement in the identification of biomarkers and diagnostic technologies in respiratory \ndiseases, partly because of the COVID-19 pandemic. Hence, investment in clinical trials with a systematic plan can help \nrepurpose thalidomide for pulmonary fibrosis.\nGraphical Abstract"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 203
encoding: FLOAT32
metadata:
{"title": "Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis", "chroma:document": "Keywords Thalidomide\u00a0\u00b7 Idiopathic pulmonary fibrosis\u00a0\u00b7 Drug repurposing\u00a0\u00b7 Cereblon\u00a0\u00b7 Anti-inflammatory\nIntroduction\nIdiopathic pulmonary fibrosis (IPF) is a progressive intersti-\ntial lung disease characterized by chronic fibrotic scarring \nof lung tissues, leading to a deterioration of lung function \n * Yogendra Nayak \n \nyogendra.nayak@manipal.edu\n1 \nDepartment of\u00a0Pharmacology, Manipal College \nof\u00a0Pharmaceutical Sciences, Manipal Academy of\u00a0Higher \nEducation, Manipal, Karnataka\u00a0576104, India"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 204
encoding: FLOAT32
metadata:
{"title": "Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth", "chroma:document": "Linking Individual Differences in Personalized Functional \nNetwork Topography to Psychopathology in Youth\nZaixu Cui,\nAdam R. Pines,\nBart Larsen,\nValerie J. Sydnor,\nHongming Li,\nAzeez Adebimpe,\nAaron F. Alexander-Bloch,\nDani S. Bassett,\nMax Bertolero,\nMonica E. Calkins,\nChristos Davatzikos,\nDamien A. Fair,\nRuben C. Gur,\nRaquel E. Gur,\nTyler M. Moore,\nSheila Shanmugan,\nRussell T. Shinohara,\nJacob W. Vogel,\nCedric H. Xia,\nYong Fan,\nTheodore D. Satterthwaite\nPenn Lifespan Informatics and Neuroimaging Center (ZC, ARP, BL, VJS, AA, MB, SS, JWV, \nCHX, TDS); Departments of Psychiatry (ZC, ARP, BL, VJS, AA, AFA-B, DSB, MB, MEC, \nRCG, REG, TMM, SS, JWV, CHX, TDS) and Radiology (HL, CD, RCG, REG, YF); Center for \nBiomedical Image Computation and Analytics (HL, CD, RCG, REG, RTS, YF, TDS); Departments \nof Bioengineering (DSB, CD), Neurology (DSB, RCG, REG), Electrical and Systems Engineering \n(DSB, CD), Physics and Astronomy (DSB); and the Penn Statistics in Imaging and Visualization \nCenter (RTS, TDS), Department of Biostatistics, Epidemiology and Informatics, University of \nPennsylvania; Department of Child and Adolescent Psychiatry and Behavioral Science (AFA-B), \nThe Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania; Santa Fe Institute (DSB), \nSanta Fe, New Mexico; Masonic Institute for the Developing Brain (DAF), Institute of Child \nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).\nAddress correspondence to Zaixu Cui, Ph.D., at cuizaixu@cibr.ac.cn, or Theodore D. Satterthwaite, M.D., M.A., at \nsattertt@pennmedicine.upenn.edu. \nSupplementary material cited in this article is available online at https://doi.org/10.1016/j.biopsych.2022.05.014.\nHHS Public Access\nAuthor manuscript\nBiol Psychiatry. Author manuscript; available in PMC 2023 March 27.\nPublished in final edited form as:\nBiol Psychiatry. 2022 December 15; 92(12): 973\u2013983. doi:10.1016/j.biopsych.2022.05.014.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 205
encoding: FLOAT32
metadata:
{"title": "Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19", "chroma:document": "Hirdman\u00a0et\u00a0al. Clinical Proteomics           (2023) 20:13  \nhttps://doi.org/10.1186/s12014-023-09403-2\nRESEARCH\nOpen Access\n\u00a9 The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nClinical Proteomics\nProteomic characteristics and\u00a0diagnostic \npotential of\u00a0exhaled breath particles in\u00a0patients \nwith\u00a0COVID-19\nGabriel Hirdman1,2,3, Embla Bod\u00e9n1,2,3, Sven Kjellstr\u00f6m4, Carl\u2011Johan Fraenkel5,6, Franziska Olm1,2,3, \nOskar Hallgren1,2,3 and Sandra Lindstedt1,2,3,7* \nAbstract \nBackground SARS\u2011CoV\u20112 has been shown to predominantly infect the airways and the respiratory tract and too \noften have an unpredictable and different pathologic pattern compared to other respiratory diseases. Current clinical \ndiagnostical tools in pulmonary medicine expose patients to harmful radiation, are too unspecific or even invasive. \nProteomic analysis of exhaled breath particles (EBPs) in contrast, are non\u2011invasive, sample directly from the pathologi\u2011"}


