# embeddings_queue

created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1227
encoding: FLOAT32
metadata:
{"title": "Transient inaccuracy in reaching parietal lobe lesion", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1984;47: 1016-1019\nTransient inaccuracy in reaching caused by a posterior\nparietal lobe lesion\nJOSE M FERRO\nFrom the Neurobehavioral Unit, Centro de Estudos Egas Moniz, Department ofNeurology, Hospital de Santa\nMaria, Lisbon, Portugal\nSUMMARY A transient disturbance of manual reaching in both hemispaces associated with a small\ncontralateral posterior perietal lobe (area 7) lesion is described. This defect was increased when\nthe patient tried to reach without viewing of the affected arm. Inacurate reaching is a distinct\nsyndrome from visuomotor or optic ataxia, and is interpreted as a failure in guiding the arm\ntowards specific sites of the space.\nInaccurate reaching and manual ataxia are consis-\ntent findings after posterior parietal lesions in the\nmonkey.'-' This defect is confined to the limbs con-\ntralateral to the lesion. In humans unimanual reach-\ning defects affecting both visual fields are very rare\nand unilateral posterior parietal lesions usually pro-\nduce visuomotor ataxia of one or both hands in the\ncontralateral half-field.'-'\nTzavaras and Masure,'\"\nLevine,\nKauffman and\nMohr,'3\nPerenin\net\nal14\ndescribed patients who were mostly impaired when\nthey tried to reach with the contralesional arm into\nboth half-fields. Misreaching was interpreted by\nLevine et al'4 as due to a loss of posterior parietal\nneurons subserving a supramodal function of integ-\nration of visual and upper extremity sensory and\nmotor information.\nWe report a patient who had a similar but trans-\nient disorder of reaching caused by a small ischaemic\nleft posterior parietal lesion.\nCase report\nA\n73-year-old\nright-handed\nwoman\ncame\nto\nthe\nemergency room of our hospital complaining of speech\ndisturbance, incoordination of her right hand and of bump-\ning obstacles with her right limbs. These symptoms had\nsuddenly appeared four hours before. Blood pressure was\n110-80 mmHg and general physical examination was nega-\ntive. Neurological examination disclosed fluent speech with"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1228
encoding: FLOAT32
metadata:
{"title": "Transient inaccuracy in reaching parietal lobe lesion", "chroma:document": "abundant circumlocutions and some verbal paraphasias.\nUnderstanding\nof\noral commands\nand naming were\nAddress\nfor\nreprint\nrequests:\nJost\nM.\nFerro,\nM.D.,\nNeurobehavioral Unit, Centro de Estudos Egas Moniz, Hospital de\nSanta Maria, 1600 Lisboa, Portugal.\nReceived 25 October 1983, and in revised form 7 March 1984.\nAccepted 10 March 1984.\nimpaired but repetition was normal. There was a right\nhomonymous hemianopia, flattened right naso-labial fold,\nan old left peripheral facial palsy and a questionable right\nextensor plantar response. Limb strength, tonus and deep\ntendon reflexes were symmetrical. Manual reaching was\ndisturbed with the right hand in both hemispaces and to a\nminor degree with the left hand in the right hemispace.\n(We use the term hemispace in the sense defined by Heil-\nman and Valenstein:\"I the space to one side of the midline\nof the body).\nRoutine blood counts and serum chemistry examinations\nwere normal except for an abnormal response on a glucose\nloading test.\nFormal neuropsychological evaluations were carried out\non the 3rd, 7th and 10th days of illness. On the 3rd day\nafter onset language disturbance assessed with a standar-\ndised aphasia battery'6 was very mild: spontaneous speech\nwas fluent and anomic, confrontation naming was moder-\nately impaired (10 out of 16 objects). Aural comprehen-\nsion and word and sentence repetition were normal. The\npatient showed very severe alexia, agraphia and contruc-\ntional disability: she could neither read or copy (with either\nhand) letters and her own name, nor copy (with either\nhand) simple drawings. Her performance on the Benton\nFogel Test of three-dimensional constructional praxis was\nvery poor: she scored 4/29 and presented \"closing-in\"\nphenomenon. She showed no bucco-facial or limb apraxia,\nbut she was somewhat clumsy when manipulating objects\nwith the right hand. She still presented a right homonym-\nous hemianopia and right threat reflex was absent. Visual\nfixation, spontaneous conjugate eye movements, slow and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1229
encoding: FLOAT32
metadata:
{"title": "Transient inaccuracy in reaching parietal lobe lesion", "chroma:document": "saccadic pursuit were normal. Optokinetic nystamus was\ndiminished to the right. Right hand strength and sensation\nwere normal. However, even with free eye and head\nmovements, when she attempted\nto reach\nfor\nvisual\ntargets, (for example, trying to grasp the examiner's index\nfinger with her index finger and thumb) her right hand\nperformance was impaired in both hemi-spaces, while the\nleft hand performance\nwas\naccurate. When\nfree eye\n1016"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1230
encoding: FLOAT32
metadata:
{"title": "Behavioural manifestations of third ventricular colloid", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1984;47:1075-1080\nBehavioural manifestations of third ventricular\ncolloid cysts\nJEFFREY M LOBOSKY,* JOHN C VANGILDER,* ANTONIO R DAMASIOt\nFrom the Department ofSurgery (Division of Neurosurgery*), and Department ofNeurology (Divisioni of\nBehavioural Neurologyt), The University of Iowa College of Medicine, Iowa City, Iowa, USA\nSUMMARY Three patients with third ventricular colloid cysts manifested disturbances of memory,\nemotion and personality in the absence of hydrocephalus. All three patients demonstrated\nsignificant improvement following removal of the tumours. The symptoms and signs associated\nwith these neoplasms may be attributed to compression or vascular compromise of the diencepha-\nlon with disorder of major limbic system structures. Tumour removal should be undertaken in\npatients with symptoms even in the absence of hydrocephalus, and ventricular shunting may be\ninadequate as a sole therapeutic measure.\nColloid cysts of the third ventricle are uncommon,\ncomprising less than 1% of intracranial neoplasms.\nInitially described by Wallmann'\nin\n1858,\nthey\nremained no more than a pathologic curiosity until\nDandy's2 first successful operative removal of this\ntumour in 1921. These midline masses are benign\nand\nlend\nthemselves\nto complete removal\nwith\nminimal morbidity and mortality utilising micro-\nscopic surgical techniques.\nColloid tumours afflict males and females with\nequal frequency. They have been reported between\nthe age extremes of 2 months and 79 years but most\nbecome symptomatic between the third and fifth\ndecades of life. The cysts range in size from 0-3 to 9\ncm but the majority are found to be between 1 and 3\ncm\nin diameter.\nSjovall3\ninitially postulated the\nparaphysis as the site of origin of these tumours but\nthis\ntheory\nwas\nlater\nchallenged\nby\nKappers.4\nShuangshoti5 subsequently suggested that the cysts\narise from infolding of the neuroepithelium which\nlines the ventricular cavities thus accounting for"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1231
encoding: FLOAT32
metadata:
{"title": "Behavioural manifestations of third ventricular colloid", "chroma:document": "their occurrence in areas other than the anterior\nthird ventricle. Most neuropathologists concur with\nthis latter theory of pathogenesis.\nThe symptomatology of colloid cysts is protean\nand the classical history of positional headache with\nintermittent apoplectic episodes is rare. Nonethe-\nAddress for reprint requests: Jeffrey M Lobosky, MD, Division of\nNeurosurgery, The University of Iowa Hospitals and Clinics, Iowa\nCity, Iowa 52242, USA.\nReceived 31 January 1984\nAccepted 10 March 1984\nless, headache is the most consistent complaint and\nis usually related to accompanying hydrocephalus.\nVenous distention secondary to compression of the\ndeep cerebral veins or their tributaries has also been\npostulated as a contributing cause of the cephal-\ngia.67\nLess attention has been focused upon the abnor-\nmal behavioural manifestations of this disorder and\nearly authors-5I\nconsidered the neuropsychological\ndisturbances to be a reflection of ventricular dilata-\ntion. Others' \"12-'4 have noted a similarity between\nthe mental decline in patients with colloid cysts and\nin those with normal pressure hydrocephalus. Thus,\na\ncausative\nrelationship\nbetween\nthe\ntwo\nhas\nbecome\naccepted. The\nalternative\npossibility\nof\ndiencephalic dysfunction from the tumour has been\nlargely ignored.\nYenerman,'4\nin his review of 54 patients with\nneuroepithelial cysts, agreed that hydrocephalus was\nthe most likely cause for the frequently observed\ndementia. He and others6\"\n14 added, however, that\npressure effects from the tumour on diencephalic\nstructures might play a significant aetiologic role. In\nthis report we describe three patients with colloid\ncysts of the third ventricle whose findings may help\nelucidate the role of diencephalic dysfunction in the\ngeneration of abnormal behavioUral symptoms.\nCase reports\nCase 1\nIn June, 1980. a 64-year-old housewife was investigated\nfor a 3 year history of progressive gait difficulty and uri-\n1075"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1232
encoding: FLOAT32
metadata:
{"title": "Cerebellar degeneration in dominantly inherited spastic paraplegia", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:145-149\nCerebellar degeneration in dominantly inherited\nspastic paraplegia\nCL SCHOLTZ, M SWASH\nFrom the Departments ofNeuropathology and Neurology, The London Hospital and The London Hospital\nMedical College, London, UK\nSUMMARY The clinical features of five affected members in three generations of a family with\ndominantly inherited Strumpell's spastic paraplegia are described, together with the pathological\nfindings in two cases. The late presentation and slow progression of the disease encompass\nfeatures of the types I and II of other authors illustrating the heterogeneous expression of the\ndisorder. Cerebellar involvement was evident clinically and pathologically.\nHereditary spastic paraplegia is a disorder character-\nised by slowly increasing spasticity and weakness of\nthe lower limbs.' Since Seeligmuller s original study2\nand the reports of Strumpell34 and Lorrain5 approx-\nimately 200 families with the disorder have been\ndescribed.6\" Pathologically\nit is characterised by\ndegeneration of the corticospinal tracts and, to a\nlesser extent, of the posterior columns.' 67 It may\npresent as a pure form, \"Strumpell-Lorrain Dis-\nease\" ,\nin which degeneration of the corticospi-\nnal\ntracts occurs below\nthe decussation\nof the\npyramids,7 or as a complicated form in which there is\nextension of the disease process into other neuronal\nsystems.8 In the latter, optic nerve involvement and\nretinal\ndegeneration\nhave\nbeen\ndescribed\nand\nextrapyramidal features, distal atrophy of the upper\nlimbs, and dementia may also occur.9 Mild cerebel-\nlar ataxia may occur in the arms in some cases, but\nataxia of gait is uncommon.'0 Hereditary spastic\nparaplegia is of adult onset and progression is slow;\nlongevity is usually unimpaired.\nTwo forms of pure dominantly inherited spastic\nparaplegia have been recognised.78 In the Type 1\nform, spasticity of the lower limbs is more marked\nthan weakness. In this group of patients there is usu-\nally a history of delay in developmental milestones,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1233
encoding: FLOAT32
metadata:
{"title": "Cerebellar degeneration in dominantly inherited spastic paraplegia", "chroma:document": "particularly in walking, and the disorder usually pre-\nsents before the age of 35 years. Progression is slow\nand disability variable. In the Type 2 form muscle\nweakness, distal sensory loss and urinary urgency or\neven incontinence may be evident. This form usually\nAddress for reprint requests: Dr M Swash, The London Hospital,\nWhitechapel, London El 1BB, UK.\nReceived 3 April 1984 and in revised form 19 July 1984.\nAccepted 21 July 1984\npresents after the age of 35 years but progresses\nmore rapidly resulting in more disability than in the\nType 1 form. Families affected by a similar disorder,\nbut inherited as an autosomal recessive trait have\nalso been reported, but this mode of inheritance is\nuncommon.8 \" Many of these latter families show\nother features,\nin addition to corticospinal\ntract\ninvolvement.8\nIn\nthis\nreport we\ndescribe\nthe\nclinical\nand\npathological features of. a late-onset, dominantly\ninherited form of the disease in which ataxia accom-\npanied severe spastic paraplegia.\nClinical features\nThe family tree is illustrated in fig 1.\nGeneration II (six members; one affected)\nI.1. female, I1.2. female, I1.3. female. Died in infancy\ncause unknown.\nII.4. female. Died aged 83 yr. She was bedridden for many\nyears before her death. Postmortem examination carried\nout 40 years ago at another hospital showed degeneration\nof the\nlateral columns and spinocerebellar\ntracts. No\nfurther details are known'\n11.5. female. Died in childhood.\n11.6. male. Died aged 36 yr of pulmonary tuberculosis.\nGeneration III (six members; two affected)\n111.1. female. Died aged 60 yr of pneumonia and renal\ndisease.\n111.2. female. Presented aged 50 yr with gradually progres-\nsive spastic paraplegia. She required a wheelchair by the\nage of about 70 years. No cerebellar ataxia was observed in\nthe arms. Eye movements and vision were normal. She\ndied at the age of 84 years. Postmortem examination was\nperformed.\n111.3. female. Died aged 5 yr of meningitis.\n145"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1234
encoding: FLOAT32
metadata:
{"title": "Ultrastructure of cerebral arteries following experimental subarachnoid haemorrhage", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:256-262\nUltrastructure of cerebral arteries following\nexperimental subarachnoid haemorrhage\nJD PICKARD,* DI GRAHAM,t ELIZABETH MATEAR,t P MACPHERSON,t\nA TAMURA, W FITCH\u00a7\nFrom the Departments ofNeurosurgery, * Neuropathology, t Neuroradiologyt and Neuroanaesthesia\u00a7\nInstitute ofNeurological Sciences, Southern General Hospital, Glasgow, Scotland, UK\nSUMMARY Scanning and transmission electron microscopy have been used to examine the ultra-\nstructure of cerebral arteries taken from dogs up to nine days following the injection of autolog-\nous blood into the suprachiasmatic cistern and using meticulous perfusion-fixation technique. No\nultrastructural changes in the cerebral arteries were noted either at sites of radiologically demon-\nstrated arterial constriction or elsewhere. The only abnormality noted was the presence of some\nleucocytes and macrophages in the subarachnoid space surrounding the arteries. These results are\ndiscussed in relation to changes in cerebrovascular reactivity that occur at this stage following\nsubarachnoid haemorrhage.\nPost-mortem studies in man have revealed that\nwhere death occurs at least three weeks after sub-\narachnoid haemorrhage, there may be subendothel-\nial infiltration with lymphocytes and macrophages\nfollowed by fibrosis localised to the segment of\nartery shown previously to be in spasm by angiogra-\nphy.'-3 Where death occurs earlier there may be\nsome inflammatory changes within the adventitia\nand possibly some necrosis within the tunica media.\nControversy has arisen over whether or not such\nstructural changes are reproducible in laboratory\nanimals. Three types of experimental subarachnoid\nhaemorrhage have been used: the cisternal injection\nof autologous blood; the rupture of an intracranial\nartery and the application of high concentrations of\nspasmogenic agents directly onto a cerebral artery.\nWithin days, at least in the subhuman primate and\nthe dog, the changes described included swelling and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1235
encoding: FLOAT32
metadata:
{"title": "Ultrastructure of cerebral arteries following experimental subarachnoid haemorrhage", "chroma:document": "separation of endothelial cells from the internal elas-\ntic lamina and degeneration of some smooth muscle\ncells. However, more recent work using the techni-\nque of cisternal injection of autologous blood has\nfailed to replicate these findings in the cat, dog and\nbaboon\n(see\ndiscussion\nfor\nreferences).\nThis\nAddress for reprint requests: Mr JD Pickard, Wessex Neurological\nCentre, Southampton General Hospital, Shirley, Southampton\nS09 4XY, UK.\nDr A Tamura: present address, Dept of Neurosurgery, Teiko Uni-\nversity Hospital, 2-11-1 Kaga Itaboshi-Ku, Tokyo, Japan.\nReceived 30 May 1984 and in revised form 31 July 1984.\nAccepted 6 August 1984\nmethod, however, is known to induce changes in the\nresponsiveness of the cerebral circulation to hyper-\ncapnia and drug induced hypotension, when studied\none week later both in the baboon and dog and is\nassociated with abnormal CSF prostanoid levels.46\nThe aim of our study was to determine whether\nsuch \"physiological\" changes are associated with\nultrastructural changes in the cerebral arteries. A\npossible explanation for the contradictory results in\nthe literature might be poor fixation and hence we\npaid particular attention to the technique of perfu-\nsion fixation in order to correlate the scanning and\ntransmission electron microscopic appearances with\nthe angiographic findings.\nMaterial and methods\nGeneral preparation\nTwenty-three adult mongrel dogs of either sex were used\nweighing between nine and 25 kg. There were three\ncategories of dogs, namely three controls, seven acute and\nthirteen chronic preparations. The animals were starved\novernight and on the day of the experiment anaesthesia\nwas induced with intravenous sodium thiopentone (10-30\nmg/kg iv). The animals were intubated and allowed to\nbreathe spontaneously on a mixture of 70% nitrous oxide\nand 30% oxygen. Under sterile conditions a femoral artery\nwas exposed and a headhunting catheter inserted. Using an\nimage intensifier this was guided into a common carotid\nartery and angiography performed by injecting 5 ml of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1236
encoding: FLOAT32
metadata:
{"title": "Ultrastructure of cerebral arteries following experimental subarachnoid haemorrhage", "chroma:document": "contrast (300 mglIml) when taking lateral subtraction\nviews.\n256"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1237
encoding: FLOAT32
metadata:
{"title": "The limbic system and the localisation of herpes simplex encephalitis", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:297-301\nOccasional review\nThe limbic system and the localisation of herpes\nsimplex encephalitis\nANTONIO R DAMASIO,* GARY W VAN HOESEN*t\nFrom the Departments ofNeurology* and Anatomyt, University ofIowa College of Medicine, Iowa City,\nIowa, USA\nSUMMARY The selective destruction of temporal and frontal lobe structures by herpes simplex\nencephalitis has been explained as a consequence of the proximity of those regions to the point of\nentry of the virus in the encephalon, through olfactory pathways or meningeal branches of the\ntrigeminal nerves. An alternative hypothesis is presented: that the encephalitis is due to a special\naffinity of the herpes simplex Type 1 virus for the limbic cortices, that is, that distinctive\nneuroanatomical, neurochemical and neuroimmunological properties of those cortices permit the\nvirus to manifest its destructive behaviour, regardless of the route of entry to the CNS, possibly\nduring altered immunological states. The study of the neurochemical and neuroimmunological\nproperties of the limbic cortices may be a useful approach to the enigma of why and when herpes\nsimplex Type 1 causes encephalitis.\nDespite some advances in antiviral therapy, herpes\nsimplex encephalitis is still a devastating and often\nfatal disease.' Patients who survive do so with major\ndefects of memory and affect, often incompatible\nwith personal and social rehabilitation. The agent of\nthe encephalitis, the herpes simplex virus Type 1,\nresides latent, possibly for many years, in the trigem-\ninal ganglia of its victims.2 4 But the reason why the\nvirus abandons its dormant state to invade and des-\ntroy the central nervous system remains a mystery.\nIt is also not known why the virus selectively dam-\nages some neural structures of the temporal and\nfrontal lobes and spares most other cortices, gray\nmatter nuclear masses and related white matter.\nConsidering that infection with herpes simplex virus\nType 1 is highly prevalent in humans, it is important"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1238
encoding: FLOAT32
metadata:
{"title": "The limbic system and the localisation of herpes simplex encephalitis", "chroma:document": "to discover (a) why the virus turns from relatively\nbenign tenant to malignant invader, (b) the route\nAddress for reprint requests: Antonio R Damasio, MD PhD,\nDepartment of Neurology. University of Iowa Hospitals & Clinics,\nIowa City, IA 52242, USA.\nReceived 8 June 1984 and in revised form 6 September 1984.\nAccepted 18 September 1984\nThis work was supported by NINCDS Grant P01 NS 19632-01.\ntaken to invade the central nervous system, and (c)\nthe reasons why a specific set of neural structures is\nconsistently chosen as target. In this article we\naddress the latter two issues.\nThe first explanation proposed for the unique\nlocalisation of herpes simplex encephalitis invoked\nintranasal inoculation and spread along the olfactory\npathways into the nearby temporal and frontal cor-\ntices.5 More recently, Davis and Johnson advanced\nanother explanation.6 They postulated that from its\nlatent site in the trigeminal ganglia, the virus would\ntravel through the tentorial branches of the trigemi-\nnal nerve in the direction of the dura mater. Because\nthe tentorial nerves supply the dura mater in both\nthe middle and anterior fossae, in and about the\nareas that the mesial and polar temporal lobes and\nthe inferior surface of the frontal lobes directly over-\nlie,' the virus would then travel in cell to cell contact\nacross the meninges and into the subjacent cortices.\nBoth explanations are plausible but they do not\nacknowledge (a) that the structures damaged by\nherpes simplex encephalitis are part of an anatomi-\ncal and functional neural unit, the limbic system; (b)\nthat the boundaries of that anatomical system are\nrespected, often faithfully, by the destructive pro-\ncess; (c) that if the location of damage would be due\n297"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1239
encoding: FLOAT32
metadata:
{"title": "Cholinergic correlates of cognitive impairment in Parkinson' disease: comparisons with Alzheimer' disease", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:413-421\nCholinergic correlates of cognitive impairment in\nParkinson' s disease: comparisons with Alzheimer' s\ndisease\nELAINE K PERRY,* MICHAEL CURTIS,t DAVID J DICK,t JOHN M CANDY,\u00a7\nJOHN R ATACK,* CLIVE A BLOXHAM,* GARRY BLESSED,II ANDREW FAIRBAIRN,**\nBERNARD E TOMLINSON,* ROBERT H PERRY\u00a7\nFrom the Department ofNeuropathology, Newcastle General Hospital; * Department ofPathology, Royal\nVictoria Infirmary; t Regional Neurological Centre, Newcastle General Hospital; t MRC Neuroendocrinology\nUnit, Newcastle General Hospital; \u00a7 Psychogeriatric Unit, Newcastle General Hospitall and St Nicholas\nHospital, Newcastle Upon Tyne,** UK\nSUMMARY Dementia in Parkinson's disease has previously been attributed to the presence in the\ncerebral cortex of Alzheimer-type neuropathological abnormalities. New evidence suggests,\nhowever, that dementia in this disease usually occurs in the absence of substantial Alzheimer-\ntype changes in the cortex and may be related to abnormalities in the cortical cholinergic system.\nThus, in Parkinsonian patients with dementia there were extensive reductions of choline acetyl-\ntransferase and less extensive reductions of acetylcholinesterase in all four cortical lobes. Choline\nacetyltransferase reductions in temporal neocortex correlated with the degree of mental impair-\nment assessed by a test of memory and information but not with the extent of plaque or tangle\nformation. In Parkinson's but not Alzheimer's disease the decrease in neocortical (particularly\ntemporal) choline acetyltransferase correlated with the number of neurons in the nucleus of\nMeynert suggesting that primary degeneration of these cholinergic neurons may be related,\ndirectly or indirectly, to declining cognitive function in Parkinson's disease.\nEvidence of an involvement of the transmitter,\nacetylcholine, in memory' 2 has stimulated investiga-\ntion of the cholinergic system in disorders of the\nhuman brain affecting memory and other cognitive"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1240
encoding: FLOAT32
metadata:
{"title": "Cholinergic correlates of cognitive impairment in Parkinson' disease: comparisons with Alzheimer' disease", "chroma:document": "functions. An abnormality of the cholinergic system\nin Alzheimer-type dementia is now well established\nand correlations between the severity of the disease\n(assessed either neuropathologicallly or clinically)\nand reductions in the cortical cholinergic enzyme,\ncholine\nacetyltransferase\n(CAT),\nhave\nbeen\nreported.34 Dementia or cognitive impairment also\noccurs in a significant number of patients with Par-\nkinson's disease (for review, see reference 5) and\nseveral reports have attributed the dementia to the\npresence of Alzheimer-type cortical neuropathology\nin these cases.67\nAddress for reprint requests: Dr EK Perry, Dept of Neuropathol-\nogy\nResearch,\nNewcastle\nGeneral\nHospital,\nWestgate\nRd,\nNewcastle upon Tyne, NE4 6BE, UK.\nReceived 14 February 1984 and in revised form 3 October 1984.\nAccepted 10 October 1984.\nThe condition of the cortical cholinergic system in\nParkinson's disease is unclear since some groups\nhave reported, in cases not assessed for mental func-\ntion, normal CAT\nactivities8 9\nwhereas another\ngroup has reported CAT reductions correlating with\nthe degree of dementia assessed retrospectively.'0\nWith\nrespect\nto the condition\nof the principal\ncholinergic nucleus innervating the neocortex-the\nnucleus of Meynert-there is evidence that loss of\nneurons occurs in both Parkinson's and Alzheimers\ndisease.\" 12 Whether this neuronal degeneration in\nboth diseases is closely associated with the cortical\ncholinergic abnormalities (assessed biochemically) is\nunclear although this issue is relevant to the ques-\ntion\nof whether\nsubcortical\ncholinergic\nabnor-\nmalities represent primary or secondary features of\nthe disease processes.\nThe present investigation was undertaken primar-\nily to examine the relationship between, on the one\nhand, cognitive impairment or dementia in Parkin-\nson's disease and, on the other hand, the presence\nof\ncortical\ncholinergic\nabnormalities,\ncortical\n413"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1241
encoding: FLOAT32
metadata:
{"title": "The influence of physostigmine visual-vestibular interaction in hereditary ataxias", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:977-981\nThe influence of physostigmine on visual-vestibular\ninteraction in hereditary ataxias\nCC TIJSSEN,t LJ ENDTZ,* C GOORt\nFrom the Departments ofNeurology* and Neurophysiology, t Municipal Hospital Leyenburg, The Hague,\nThe Netherlands\nSUMMARY Visual suppression of caloric nystagmus was studied in five patients with hereditary\nataxia before and after administration of physostigmine. All patients had an initial abnormal\nocular fixation index that improved after physostigmine was given. The data indicate that there is\na partly reversible disturbance of visual-vestibular interaction in patients with hereditary ataxia,\ncaused by an impairment of a central cholinergic mechanism.\nThe\nhereditary\nataxias\nconstitute\na number\nof\ndegenerative cerebellar diseases having ataxia as\ntheir common feature. The pathophysiological basis\nunderlying\nthis group of disorders\nis unknown.\nHereditary factors play an important role in their\naetiology but sporadic cases also occur.' Recent\nstudies have indicated a possible biochemical deficit.\nPrimary or secondary abnormalities of pyruvate\nmetabolism have been identified in up to 50% of\nunselected series of patients with hereditary atax-\nias,23 and in patients with Friedreich's ataxia a low-\nered activity of pyruvate oxidation caused by a\ndefect at the level of the third component of the\npyruvate\ndehydrogenase\ncomplex,\nthat\nis\nthe\nlipoamide\ndehydrogenase,\nhas\nbeen\ndemons-\ntrated.4-6 This disturbance of the pyruvate metabol-\nism\nleads\nto\nimpaired\nproduction\nof\nacetyl-\ncoenzyme A and subsequently to impaired synthesis\nof the\nneurotransmitter\nacetylcholine.26\nAcetyl-\ncholine\nsynthesis\nseems\nexquisitely\nsensitive\nto\nimpaired pyruvate oxidation.3 Clinical studies have\nsuggested that low doses of physostigmine, a cen-\ntrally active cholinesterase inhibitor, improve signs\nof ataxia\nin patients with hereditary ataxias.79\nObjective criteria to evaluate the influence of this\ndrug are however lacking.\nA\nnumber\nof\nocular\nabnormalities\noccur"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1242
encoding: FLOAT32
metadata:
{"title": "The influence of physostigmine visual-vestibular interaction in hereditary ataxias", "chroma:document": "occur\nin\nhereditary ataxias including nystagmus (especially\ngaze-evoked, rebound and downbeat nystagmus),\nimpaired smooth pursuit, saccadic dysmetria and\nPresent address and address for reprint requests: Dr CC Tijssen,\nDepartment of Neurology, St. Elisabeth Hospital, P.O. Box 90151,\n5000 LC Tilburg, The Netherlands.\nReceived 6 July 1984 and in revised form 6 November 1984.\nAccepted 12 January 1985\ndefective visual suppression of vestibular nystag-\nMUS.'0-'2 The\nability\nto suppress the vestibulo-\nocular reflex (VOR) by fixation is a valuable indica-\ntion of cerebellar pathology.'2-5 There is evidence\nthat\nthe\nvestibulo-cerebellum,\nespecially\nthe\nflocculus,\nis\nan\nimportant\nsite\nfor\nthis\nvisual-\nvestibular\ninteraction\nthat\nfacilitates\nadaptive\nchanges in the VOR.'6-2'\nIn this study we investigated the influence of the\ndrug physostigmine on the visual suppression of\ncaloric-induced vestibular nystagmus in five patients\nwith hereditary ataxia.\nMaterial and methods\nFive patients with hereditary ataxia were studied, whose\nrelevant data are summarised in the table. The patients\nused no drugs at the time of investigation. Each subject\nwas\nexamined\nwith\nelectro-nystagmography\n(ENG)\nequipment using a time constant of 5 seconds and a filter of\n15 Hz (3 dB). Horizontal eye movements were recorded\nwith surface electrodes placed near the inner and outer\ncanthus of both eyes. A voluntary eye movement over 200\nwas used for calibration of the angular velocity of the slow\nphase of the nystagmus. Caloric stimulation was applied by\nirrigating both ears with 50 ml of water at 30\u00b0C during 20\nseconds with eyes closed. If no good response was obtained\nwater at 15\u00b0C was also applied. With this procedure a max-\nimum slow phase eye velocity occurs at about 45 seconds\nafter the onset of irrigation and maintains for about 30\nseconds.25 The visual suppression test was carried out dur-\ning this maximum intensity of caloric nystagmus at 55 sec-\nonds after the onset of irrigation. The patients were asked"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1243
encoding: FLOAT32
metadata:
{"title": "The influence of physostigmine visual-vestibular interaction in hereditary ataxias", "chroma:document": "to open their eyes and fix their gaze upon a red spot light at\na distance of 11/2 metre for 15 seconds. Nystagmus fre-\nquency, amplitude and slow phase velocity, which was\naveraged over 10 wave forms, were measured before and\nafter eye opening. The maximum response during visual\n977"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1244
encoding: FLOAT32
metadata:
{"title": "A study of the relationship between neurological function and vitamin E concentrations in patients with cystic fibrosis", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1985;48: 1097-1102\nA study of the relationship between neurological\nfunction and serum vitamin E concentrations in\npatients with cystic fibrosis\nHJ WILLISON,* DPR MULLER,t S MATTHEWS,t S JONES,t A KRISS, RJ STEAD,*\nME HODSON,* AE HARDINGt\nFrom Brompton Hospital and the Cardiothoracic Institute, * the Institute ofChild Health, t and the Institute of\nNeurology,t London, UK\nSUMMARY A patient with cystic fibrosis and undetectable serum vitamin E concentrations is\ndescribed who developed a progressive spinocerebellar syndrome and pigmentary retinopathy\nwith abnormal somatosensory and visual evoked potentials (SSEPs and VEPs). In order to assess\nthe relationship between neurological function and serum vitamin E concentrations in cystic\nfibrosis, 29 unselected patients who had no neurological symptoms were examined neurologi-\ncally. Ten were randomly selected for neurophysiological assessment by recording SSEPs and\nVEPs. Electroretinograms (ERGs) were also performed in five cases. The findings were corre-\nlated with serum vitamin E concentrations which were unknown to the neurological investigators\nprior to completion of the study. Only one patient had definite reflex and sensory abnormalities,\nand the remaining 28 were clinically normal. The ERG was abnormal in two cases, one of whom\nhad abnormal VEPs. SSEPs were normal in all 10 cases. Twenty six patients had serum vitamin E\nconcentrations below the normal range. In two of the three patients who had definite neurological\nor electrophysiological abnormalities serum vitamin E concentrations were below the median\nvalue for the whole group.\nSevere vitamin E deficiency as a consequence of pro-\nlonged fat malabsorption is now a well established\ncause of a progressive neurological disorder com-\nprising ataxia, areflexia, and proprioceptive loss.\nThis syndrome is particularly prevalent in children\nwith abetalipoproteinaemia and chronic liver dis-\nease.' It has also been reported after extensive ileal"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1245
encoding: FLOAT32
metadata:
{"title": "A study of the relationship between neurological function and vitamin E concentrations in patients with cystic fibrosis", "chroma:document": "resection23 and in a few cases of cystic fibrosis.4-6\nPathological\nstudies in man78 and experimental\nanimals9 have shown that vitamin E deficiency pro-\nduces a dying-back neuropathy in sensory neurons\nwhich affects the centrally directed fibres in the\nposterior columns more severely than the peripheral\naxons. Mild degenerative changes also occur in the\nspinocerebellar tracts.7\nReduced serum concentrations of vitamin E are\ncommon in patients with cystic fibrosis, but it is not\nAddress for reprint requests: Dr DPR Muller, Department of Child\nHealth, Institute of Child Health, 30 Guilford Street, London\nWC1N IEM.\nReceived 11 January 1985 and in revised form 26 March 1985.\nAccepted 5 April 1985\nclear how often these are of clinical or pathological\nsignificance. This paper describes a patient with\nundetectable serum vitamin E concentrations who\ndeveloped a spinocerebellar syndrome and a pig-\nmentary retinopathy. The results of a study correlat-\ning\nvitamin\nE\nstatus\nwith\nclinical\nand\nneurophysiological observations in 29 neurologi-\ncally asymptomatic cases of cystic fibrosis are also\nreported.\nCase report\nA 22-year-old woman with cystic fibrosis presented with\nmeconium ileus in infancy. She had steatorrhoea and\nrecurrent chest infections throughout childhood, and a\nnumber of episodes of jaundice before the age of five.\nHepatomegaly was first noted when she was 12, and on\ninvestigation it appeared that her liver disease resulted\nfrom chronic active hepatitis. At the age of 14 yr she com-\nplained of night blindness and was found to have a pigmen-\ntary retinopathy. This was attributed to a documented\nsevere deficiency of vitamin A but her symptoms progres-\nsed despite replacement therapy. Serum vitamin A con-\ncentrations increased but remained below the normal\n1097"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1246
encoding: FLOAT32
metadata:
{"title": "conduction velocity in the human spinal cord: slowed conduction in multiple sclerosis and radiation myelopathy", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1985;48: 1135-1139\nMotor conduction velocity in the human spinal cord:\nslowed conduction in multiple sclerosis and radiation\nmyelopathy\nSJ SNOOKS, M SWASH\nFrom St Mark's Hospital, and The London Hospital, London, UK\nSUMMARY Transcutaneous electrical stimulation of the central nervous system was used to meas-\nure motor conduction velocity in the human spinal cord in 21 subjects aged 22 to 75 years (mean\n55 years), none of whom had neurological disease. The motor conduction velocity between the\nsixth cervical (C6) and first lumbar (L1) vertebral levels was 67-4\n+ 9-1 m/s. This probably\nrepresents conduction velocity in the corticospinal tracts. In these subjects the motor conduction\nvelocity in the cauda equina, between the first lumbar (Li) and fourth lumbar (L4) vertebral\nlevels, was 57 9 + 10*3 m /s. In four of five patients with multiple sclerosis, all with corticospinal\nsigns in the legs, motor conduction velocity between C6 and Li was slowed (41-8 + 16-8 m /s), but\ncauda equina conduction was normal (55.8\n+ 7-8 m/s). Similar slowing of spinal cord motor\nconduction was found in a patient with radiation myelopathy. This method should provide a\nrelevant, simple clinical test in patients with spinal cord disease.\nThe scope of electrophysiological investigation of\nthe central nervous system is limited and, in particu-\nlar, there is no method available for assessment of\nthe motor system in the spinal cord. We have\ndevised a method for measurement of the motor\nconduction velocity in the human spinal cord by\nadapting the technique of transcutaneous electrical\nstimulation of the CNS devised by Merton and Mor-\nton.' 2 This method promises to be of considerable\npractical value in clinical practice. It also enables\nmotor conduction\nto be\nassessed\nin the cauda\nequina. In this report we present our results in nor-\nmal subjects and show that motor conduction veloc-\nity in the spinal cord is slowed in some patients with\ndemyelinating diseases.\nMethods"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1247
encoding: FLOAT32
metadata:
{"title": "conduction velocity in the human spinal cord: slowed conduction in multiple sclerosis and radiation myelopathy", "chroma:document": "Methods\nWe stimulated the spinal cord and cauda equina at C6, Li\nand L4 vertebral levels respectively using a device consist-\ning of two\n1 cm diameter saline-soaked pad electrodes\nmounted 5 cm apart. We have not found it possible, so far,\nto stimulate reliably the motor roots of the cauda equina at\nAddress for reprint requests: Dr M Swash, The London Hospital,\nLondon El lBB, UK.\nReceived 14 August 1984 and in revised form 19 November 1984.\nAccepted 23 November 1984\na lower vertebral level than L4. The subject lay in the left\nlateral position and an earth electrode was applied to the\nright upper thigh. The stimulating electrodes, mounted on\na holder, were pressed firmly against the skin overlying the\nspine at the appropriate level, in the midline, with the\ncathode caudally. Single shocks of 800-1500 volts, decay-\ning with a time constant of 50 uts, were used.2 The stimulus\ntriggered\nthe\noscilloscope\nof a Medelec MS6 EMG\napparatus through the delay line. Muscle contraction was\nobserved in response to the stimulus in the paravertebral\nand abdominal muscles and in the muscles of the buttocks\nand legs. This was perceived as a jolt, but was not painful.\nWe recorded the muscle response from the pelvic floor\nmuscles, innervated by the S3-4 myotomes3 using intra-\nanal surface electodes or, as in cases 4 and 6 (table), from\ntibialis anterior (L4-5 myotomes). Selection of a lower\nlimb muscle, for example tibialis anterior, excludes the sac-\nral component of the spinal cord from the measurement,\nbut does allow lateralisation of the response. The intra-\nanal recording electrode consisted of a modified telephone\njack placed in the anal canal adjacent to the external anal\nsphincter muscle2 or a pair of electrodes mounted on the\ntip of a rubber finger stall held digitally in the anal canal\nagainst the puborectalis bar.4 The latter technique gave the\nbetter result (fig 1).\nThe latencies from transcutaneous stimulation at C6, Li\nand L4 vertebral levels, with a constant recording site,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1248
encoding: FLOAT32
metadata:
{"title": "conduction velocity in the human spinal cord: slowed conduction in multiple sclerosis and radiation myelopathy", "chroma:document": "were used to determine latencies between C6 and Li, rep-\nresenting the length of the spinal cord from C6 to the conus\nmedullaris, and between Li and L4, representing the ros-\ntral portion of the motor roots in the cauda equina. After\n1135"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1249
encoding: FLOAT32
metadata:
{"title": "Dopamine agonists visual-cortical reflex myoclonus", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1985;48: 1277-1283\nDopamine agonists suppress visual-cortical reflex\nmyoclonus\nJA OBESO, J ARTIEDA, T TUNON,* MR LUQUIN, JM MARTINEZ LAGE\nFrom the Movement Disorders Unit, Department ofNeurology, Clinica Universitaria, University ofNavarra,\nPamplona, Spain.\nSUMMARY Two patients with a diagnosis of olivo-ponto-cerebellar atrophy developed cortical\nreflex myoclonus to visual (flash) and somaesthetic stimuli. Oral treatment with levodopa-\ncarbidopa (1000/100 mg) or subcutaneous administration of apomorphine (1 mg) abolished the\nvisually-triggered myoclonus, without modifiying reflex myoclonus to electrical or tactile stimula-\ntion. Intravenous administration of lisuride (0-1 mg) produced a marked reduction in both types\nof reflex myoclonus. These results indicate a selective inhibitory effect of dopamine agonist drugs\non visual reflex myoclonus of cortical origin.\nIn recent years the pharmacological basis of myo-\nclonus has been focused on a disorder of cerebral\nserotoninergic mechanisms. This followed the dis-\ncovery by Lhermitte\net al,' 2\nlater confirmed by\nothers,36\nthat\noral\ntreatment\nwith\n5-hydroxytryptophan (5-HTP) plus carbidopa pro-\nduced a reduction in post-anoxic action myoclonus,\nand\nthe\nfindings\nof\nlow\nCSF\nlevels\nof\n5-hydroxyindolacetic acid in similar patients who\nresponded\nto\ntreatment\nwith\n5-HTP\nor\nclonazepam.78 However, a deficit of serotonin may\nnot be important in other myoclonic disorders9 10 in\nwhich other neurotransmitters may be involved. The\nanti-myoclonic effect of clonazepam, valproic acid\nor primidone might be due at least partially, to\nenchancement of cerebral gamma aminobutyric acid\n(GABA) activity.\" A protective effect of apomor-\nphine against visually induced myoclonus has been\ndemonstrated in the baboon.'2 Quesney et al'3 found\nthat in patients with generalised epilepsy, apomor-\nphine produced transient inhibition of spike and\nwave EEG activity induced by photic stimulation,\nsuggesting a dopamine influence on certain types of\nmyoclonus."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1250
encoding: FLOAT32
metadata:
{"title": "Dopamine agonists visual-cortical reflex myoclonus", "chroma:document": "Cortical reflex myoclonus results from abnormal\n*Present address: Neuropathology section, Hospital de Navarra,\nPamplona.\nAddress for reprint requests: Dr JA Obeso, Neurologia, Clinica\nUniversitaria, Apartado 192, Pamplona, Spain.\nReceived 23 January 1985 and in revised form 9 May 1985.\nAccepted 17 May 1985\nmotor cortex activity triggered by sensory input.'4 '5\nElectrophysiological characteristics of cortical myo-\nclonus are the presence of enhanced cortical evoked\npotentials, EEG activity time-locked to the muscle\njerks and brief EMG discharges.4 12 Clinical and\nelectrophysiological studies indicate the existence of\nseparate mechanisms underlying different types of\ncortical myoclonus in man.'6 Such pathophysiologi-\ncal discrimination may also indicate different phar-\nmacological characteristics. For example, cortical\nreflex myoclonus\nto somaesthetic\nstimulation\nis\nhighly responsive to serotonin agonists, but is not\nimproved by dopaminergic drugs.'7 We now report a\nselective effect of levodopa-carbidopa and apomor-\nphine on cortical reflex myoclonus induced by photic\nstimulation\nin\ntwo\npatients\nwith\nolivo-ponto-\ncerebellar-atrophy. These two cases were included\nin a previous report on the pathophysiology of corti-\ncal myoclonus.'6\nMethod\nElectrophysiological technique\nA Medelec MS 6 machine\nwas\nused\nfor\nelectrophysiological\ninvestigations.\nSomatosensory evoked potentials (SEPs) to digital nerve\nstimulation were recorded from a scalp electrode placed on\nthe hand area (7 cm lateral and 2 cm posterior to the\nvertex) with the reference electrode on Fz (10-20 EEG\ninternational system). Visual evoked potentials (VEPs) to\nflash stimulation recorded from the scalp over the occipital\ncortex also were recorded. For reasons explained previ-\nously,'8 we have designated the major cortical potential\npeaks by their polarity and sequence (Ni, P1, N2, etc).\nThe electromyographic (EMG) reflex responses elicited by\nelectrical or flash stimulation were recorded simultane-\n1277"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1251
encoding: FLOAT32
metadata:
{"title": "Effect of ammonia intoxication cerebral blood flow, its autoregulation and responsiveness carbon dioxide and papaverine", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:302-309\nEffect of ammonia intoxication on cerebral blood\nflow, its autoregulation and responsiveness to carbon\ndioxide and papaverine\nADAM CHODOBSKI,* JOANNA SZMYDYNGER-CHODOBSKA,t\nKRYSTYNA SKOLASINSKA*\nFrom the Microcirculation Research Unit,* and Department of Physiology,t Institute of Physiological\nSciences, School of Medicine, Warsaw, Poland\nSUMMARY Cerebral blood flow (CBF) was measured in anaesthetised cats with 133Xe clearance\nmethod under normal conditions and with hyperammonaemia. Elevation of blood ammonia con-\ncentration by an intravenous infusion of ammonium acetate caused an increase in CBF and a\nparallel decrease in cerebrovascular resistance (CVR). These parameters reached, however, plateau\nat an arterial blood ammonia level exceeding 500 Mmol/l. Cerebrovascular reactivity to CO2 dimin-\nished following elevation of blood ammonia concentration and at arterial blood ammonia level\nexceeding 500 umol/l it was virtually abolished. In contrast, hyperammonaemia influenced neither\ncerebrovascular responsiveness to papaverine nor autoregulatory properties of the cerebral circu-\nlation. It is concluded, therefore, that hyperammonaemia exerts some dilatatory effect on cerebral\nvessels and severely impairs chemical regulation of CBF but does not elicit cerebral vasomotor\nparalysis.\nA pathogenic role of ammonia in hepatic encepha-\nlopathy and coma had already been recognised at the\nend of the last century.' However, the mechanisms by\nwhich hyperammonaemia affects the central nervous\nsystem are not clear. Especially, the effect ofammonia\non regulation of the cerebral blood flow (CBF) still\nremains to be elucidated.\nIn\n1976\nChandler\nand\nKindt2\ndemonstrated\nsignificant elevation of intracranial pressure (ICP) in\npatients suffering from hepatic encephalopathy of\ndifferent aetiologies. An increase in ICP by 200-300%\nof control values has also been found in rhesus mon-\nkeys during hyperammonaemia\nelicited by intra-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1252
encoding: FLOAT32
metadata:
{"title": "Effect of ammonia intoxication cerebral blood flow, its autoregulation and responsiveness carbon dioxide and papaverine", "chroma:document": "venous infusion of ammonium acetate.3 Altenau and\nKindt4 using the same experimental model have\nfound that ammonia intoxication causes an increase\nin CBF and impairs cerebrovascular reactivity to CO2\nand autoregulatory properties of cerebral circulation.\nBasing on these results, these authors have postulated\nthat ammonia intoxication brings about the cerebral\nvasomotor paralysis leading to an increase in intra-\nAddress for reprint requests: Adam Chodobski, Microcirculation\nResearch\nUnit,\nInstitute\nof Physiological\nSciences,\nSchool\nof\nMedicine, Krakowskie Przedmieicie 26/28, 00-927 Warsaw, Poland.\nReceived 23 November 1984 and in revised form 9 July 1985.\nAccepted 13 July 1985\ncranial blood volume, which in turn would produce an\nelevation of ICP.\nThe present study was undertaken to evaluate the\neffect of elevation of blood ammonia concentration\non CBF and its responsiveness to CO2. Furthermore,\ncerebrovascular reactivity to papaverine, the agent\nknown to affect cerebral vessels in a manner different\nfrom carbon dioxide, as well as autoregulatory prop-\nerties of cerebral circulation were examined under\nnormal conditions and with hyperammonaemia in\norder to elucidate whether an elevation of blood\nammonia concentration may result in the vasomotor\nparalysis of the cerebral vessels.\nMaterials and methods\nThe experiments were carried out on 82 cats of either sex\nweighing between 2 4 and 3 8 kg. Anaesthesia was induced\nwith\npentobarbital\nsodium (Nembutal-Abbott)\ninjected\nintraperitoneally in a dose of 20 mg/kg and maintained with\nintravenous alpha-chloralose (60 mg/kg). A tracheostomy\nwas performed and catheters inserted into the left femoral\nartery and vein for measurement of mean arterial blood\npressure (MABP), collection of arterial blood samples and\nintravenous administration of drugs and solutions. In the\nexperiments, in which autoregulation of CBF was examined\nthe right femoral artery was additionally cannulated for\nwithdrawal of blood to produce controlled hypotension. The\n302"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1253
encoding: FLOAT32
metadata:
{"title": "The effect on plasma prolactin levels of interictal epileptiform EEG activity", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:702-705\nShort report\nThe effect on plasma prolactin levels of interictal\nepileptiform EEG activity\nMICHAEL J AMINOFF,* ROGER P SIMON,* ECKEHART WIEDEMANNt\nFrom the Departments ofNeurology* and Medicine,t School ofMedicine, University of California, San\nFrancisco, California\nSUMMARY\nBecause of the known effects of seizures on plasma prolactin, the plasma prolactin levels\nwere measured before and after generalised interictal epileptiform activity was provoked in the EEG\nin five epileptic patients. The findings were compared with those obtained in five normal subjects\nand three epileptic patients who were also exposed to flicker stimulation, but who did not develop\na photoconvulsive EEG response. There was no significant difference in baseline prolactin values,\nand levels did not change with photic stimulation or in response to the presence of generalised\nepileptiform activity in the EEG.\nA marked increase in plasma prolactin level is known\nto occur in many patients shortly after a tonic-clonic\nseizure' -5 and may sometimes occur also following\npartial seizures.`\nHowever, the effect on plasma\nprolactin of interictal epileptiform EEG activity is un-\nknown. Epileptiform EEG discharges (that is, abnor-\nmal paroxysmal activity consisting of spike, polyspike\nor sharp wave discharges with or without associated\nslow waves) may occur without obvious clinical ac-\ncompaniments in many patients with epilepsy. Never-\ntheless such EEG discharges may be accompanied by\nan increase in reaction time, or by complete failure to\nrespond to a stimulus.8 Indeed, some authors con-\nsider that generalised spike-wave activity is always ac-\ncompanied by impaired performance.9 The likelihood\nof discerning some impairment of cerebral function\nduring the occurrence of epileptiform activity de-\npends upon the testing technique used. In particular,\nsimple motor tasks are relatively little affected by gen-\neralised spike-wave EEG activity, whereas choice re-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1254
encoding: FLOAT32
metadata:
{"title": "The effect on plasma prolactin levels of interictal epileptiform EEG activity", "chroma:document": "action time, signal detection, and short-term memory\ntasks are more sensitive.8\nAddress for reprint requests: Dr Michael J Aminoff, Room 794-M,\nDepartment of Neurology, University of California, School of\nMedicine, San Francisco, California 94143, USA.\nReceived 30 July 1985.\nAccepted 10 October 1985\nWe have examined the effect of interictal epi-\nleptiform EEG activity on plasma prolactin levels be-\ncause any change in prolactin levels under these\ncircumstances might provide further support for the\nbelief that interictal generalised epileptiform EEG\ndischarges are of functional significance. At the same\ntime, it would detract from the possible importance of\nmeasuring plasma prolactin levels when attempting to\ndetermine in epileptic patients whether clinical at-\ntacks of uncertain nature represent seizures. Finally,\nany increase in prolactin level with subclinical gener-\nalised interictal epileptiform EEG discharges might\nprovide further insight to the basis of the prolactin\nresponse accompanying seizures.\nMethods\nSpontaneous interictal epileptiform EEG activity occurs un-\npredictably, and this would preclude the taking of blood\nsamples for baseline purposes before the occurrence of such\nactivity. Accordingly we had to use some means of pro-\nvoking a generalised epileptiform discharge in the EEG, and\nthis was achieved by photic stimulation. The subject lay on\na couch in a quiet, darkened room while a 16-channel EEG\nwas recorded for one hour. A Grass intermittent photic\nstimulator was then used to cause rhythmic flash stimulation\nwhile the EEG was recorded bipolarly from a wide region of\nthe scalp including the parietal and occipital areas. Flash\nstimuli were delivered at 1, 3, 6, 9, 12, 15, 18 and 21 Hz. At\neach flash rate the EEG was recorded with the subject's eyes\n702"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1255
encoding: FLOAT32
metadata:
{"title": "This Week in The Journal", "chroma:document": "This Week in The Journal\nRetinal Pigmented Epithelium\n\u201cNibbles\u201d Away Outer Segment\nTips\nAnkita Umapathy, Gil Torten, Antonio\nE. Paniagua, Julie Chung, Madeline\nTomlinson, et al.\n(see pages 2653\u20132664)\nThe retinal pigmented epithelium (RPE)\nserves a remarkable support role in the\nretina, nourishing and maintaining pho-\ntoreceptor cells in ways that are crucial\nfor vision. This includes \u201cnibbling\u201d away\nat the tips of the outer segment (OS) of\nrods and cones. Photoreceptors are made\nup of stacks of membranous discs that\ncontain photoreceptive proteins. As these\ndiscs are added at the base of the OS,\nthe tip must be removed and recycled\nto make way. Deficits in this membrane\ningestion and degradation by the RPE\ncan lead to retinal degradation and blind-\nness. Scientists have long marveled at this\nprocess, but little is known about how it\noccurs, although some proteins required\nfor the activity have been identified. Now,\nUmapathy et al. investigate using high-\nspeed 3D live-cell imaging in mice to vis-\nualize the spatiotemporal details of the\nphagocytic event. The researchers created\na culture of primary RPE cells together\nwith OSs and then transiently transfected\nRPEs with F-tractin-RFP to label actin\nfilaments. Peak coordinated ingestion\noccurred over 30\u201345 min but could be\nobserved for up to 90 min. Actin fila-\nments extended apical membranes from\nRPE cells, which enveloped the tip of an\nOS and engulfed the separated cellular\nmatter, suggesting a scission event medi-\nated by dynamic actin filaments. The\nspecific events suggested a process called\ntrogocytosis. Inhibition of actin poly-\nmerization prolonged but did not pre-\nvent the scission process. The authors\nthen honed in on which proteins played a\npart in the scission events\u2014specifically the\nBin-Amphiphysin-Rev domain-contain-\ning proteins formin-binding protein\n17 (FBP17) and amphiphysin-1 (AMPH1),\nwhich sense and bind to curved mem-\nbranes and can induce further curvature.\nLive imaging revealed that fluorescently la-\nbeled FBP17 and AMPH1 were associated"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1256
encoding: FLOAT32
metadata:
{"title": "This Week in The Journal", "chroma:document": "with membrane \u201ccups\u201d of RPE cells con-\ntaining OS tips, albeit in slightly different\nlocalization patterns. The study finds once\nand for all that, rather than the OS pas-\nsively shedding its distal discs for phagocy-\ntosis, RPE cells actively trogocytose, or\nnibble away, the tips.\nAbstract Sequential Monitoring\nOccurs in the Prefrontal Cortex\nNadira Yusif Rodriguez, Theresa H.\nMcKim, Debaleena Basu, Aarit Ahuja,\nand Theresa M. Desrochers\n(see pages 2741\u20132755)\nImagine walking into a kitchen stocked\nwith ingredients, tools, and appliances\u2014\nbut to make a successful meal, you\u2019ll need\na recipe. The cognitive processes needed\nto keep track of such sequential, abstract\ninstructions requires an active process\ncalled sequence monitoring. The neural\nunderpinnings of such abstract monitor-\ning remain mostly unknown, but brain-\nimaging studies in humans indicate that it\nincludes activity in the left or bilateral ros-\ntrolateral prefrontal cortex (RLPFC), and\nstudies in nonhuman primates suggest\nthat the dorsolateral PFC (DLPFC) medi-\nates abstract thought and sequential in-\nformation. This week, Yusif Rodriguez\net al. explore the possibility in monkeys\nthat area 46 of the DLPFC, an area an-\nalogous to human RLPFC, monitors\nabstract visual sequential information.\nThe authors conducted functional mag-\nnetic resonance imaging in three awake\nadult male rhesus macaque monkeys\nthat fixated on a central spot while\nviewing fractal images in four-item\nvisual sequences. No responses were\nrequired, and monkeys received con-\ntinuous liquid reward as long as they\nmaintained fixation.\nVisual\nstimuli\nwere presented in blocks that either\nfollowed or deviated from sequential\nrules. The imaging data suggested that\nboth the right and left sides of area 46\nof DLPFC monitors abstract visual\nsequence structure. Interestingly, the\nright and left sides seemed to track the\nabstract information with differing dy-\nnamics, with onset-based activity on the\nright and ramping dynamics during\nthe presentation on the left. Importantly,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1257
encoding: FLOAT32
metadata:
{"title": "This Week in The Journal", "chroma:document": "the data show that similar brain areas in\nhumans and nonhuman primates mediate\nabstract sequence monitoring, although\nin humans the activity is more consistent\nbilaterally. The work brings us a step\ncloser to deciphering the neural sub-\nstrates of abstract sequential cognitive\nprocesses.\nThisWeekinTheJournalwaswrittenbyStephaniSutherland\nhttps://doi.org/10.1523/JNEUROSCI.twij.43.15.2023\nInset, fluorescently labeled f-actin (red) of a phagocytic cup\nengulfing the tip of an OS labeled with antibody (green);\nthe larger image is a 3D rendering of the interaction.\n2630 \u2022 The Journal of Neuroscience, April 12, 2023 \u2022 43(15):2630"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1258
encoding: FLOAT32
metadata:
{"title": "Hindbrain Adenosine 5-Triphosphate (ATP)-Purinergic Signaling Triggers LH Surge and Ovulation via Activation of AVPV Kisspeptin Neurons in Rats", "chroma:document": "Systems/Circuits\nHindbrain Adenosine 5-Triphosphate (ATP)-Purinergic\nSignaling Triggers LH Surge and Ovulation via Activation of\nAVPV Kisspeptin Neurons in Rats\nNaoko Inoue,p Safiullah Hazim,p Hitomi Tsuchida, Yuri Dohi, Ren Ishigaki, Ai Takahashi, Yuki Otsuka,\nKoki Yamada, Yoshihisa Uenoyama, and Hiroko Tsukamura\nLaboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan\nOvulation disorders are a serious problem for humans and livestock. In female rodents, kisspeptin neurons in the anteroven-\ntral periventricular nucleus (AVPV) are responsible for generating a luteinizing hormone (LH) surge and consequent ovula-\ntion. Here, we report that adenosine 5-triphosphate (ATP), a purinergic receptor ligand, is a possible neurotransmitter that\nstimulates AVPV kisspeptin neurons to induce an LH surge and consequent ovulation in rodents. Administration of an ATP\nreceptor antagonist (PPADS) into the AVPV blocked the LH surge in ovariectomized (OVX) rats treated with a proestrous\nlevel of estrogen (OVX 1 high E2) and significantly reduced the ovulation rate in proestrous ovary-intact rats. AVPV ATP\nadministration induced a surge-like LH increase in OVX 1 high E2 rats in the morning. Importantly, AVPV ATP administra-\ntion could not induce the LH increase in Kiss1 KO rats. Furthermore, ATP significantly increased intracellular Ca21 levels in\nimmortalized kisspeptin neuronal cell line, and coadministration of PPADS blocked the ATP-induced Ca21 increase.\nHistologic analysis revealed that the proestrous level of estrogen significantly increased the number of P2X2 receptor (an\nATP receptor)-immunopositive AVPV kisspeptin neurons visualized by tdTomato in Kiss1-tdTomato rats. The proestrous\nlevel of estrogen significantly increased varicosity-like vesicular nucleotide transporter (a purinergic marker)-immunopositive\nfibers projecting to the vicinity of AVPV kisspeptin neurons. Furthermore, we found that some hindbrain vesicular nucleotide"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1259
encoding: FLOAT32
metadata:
{"title": "Hindbrain Adenosine 5-Triphosphate (ATP)-Purinergic Signaling Triggers LH Surge and Ovulation via Activation of AVPV Kisspeptin Neurons in Rats", "chroma:document": "transporter-positive neurons projected to the AVPV and expressed estrogen receptor a, and the neurons were activated by\nthe high E2 treatment. These results suggest that hindbrain ATP-purinergic signaling triggers ovulation via activation of\nAVPV kisspeptin neurons.\nKey words: estrogen-positive feedback; GnRH/LH surge; kisspeptin neuron\nSignificance Statement\nOvulation disorders, which cause infertility and low pregnancy rates, are a serious problem for humans and livestock. The\npresent study provides evidence that adenosine 5-triphosphate, acting as a neurotransmitter in the brain, stimulates kisspep-\ntin neurons in the anteroventral periventricular nucleus, known as the gonadotropin-releasing hormone surge generator, via\npurinergic receptors to induce the gonadotropin-releasing hormone/luteinizing hormone surge and ovulation in rats. In addi-\ntion, histologic analyses indicate that adenosine 5-triphosphate is likely to be originated from the purinergic neurons in the\nA1 and A2 of the hindbrain. These findings may contribute to new therapeutic controls for hypothalamic ovulation disorders\nin humans and livestock.\nReceived July 26, 2022; revised Dec. 15, 2022; accepted Feb. 8, 2023.\nAuthor contributions: N.I. and H. Tsukamura designed research; N.I., S.H., H. Tsuchida, Y.D., R.I., A.T., and K.Y.\nperformed research; N.I., S.H., Y.D., R.I., A.T., Y.O., K.Y., and Y.U. contributed unpublished reagents/analytic tools; N.I.,\nS.H., H. Tsukamura, Y.D., R.I., A.T., Y.O., K.Y., Y.U., and H. Tsukamura analyzed data; N.I., S.H., Y.U., and H. Tsukamura\nwrote the paper.\nThis work was supported in part Japan Society for the Promotion of Science a Grant-in-Aid for a Research\nFellow KAKENHI Grants 19H03103 to N.I., 20H03127 to Y.U., and 18H03973 and 21H05031 to H. Tsukamura;\nthe Naito Foundation to N.I.; and Nagoya University Interdisciplinary Frontier Fellowship supported by Nagoya\nUniversity and JST, the establishment of university fellowships towards the creation of science technology"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1260
encoding: FLOAT32
metadata:
{"title": "Hindbrain Adenosine 5-Triphosphate (ATP)-Purinergic Signaling Triggers LH Surge and Ovulation via Activation of AVPV Kisspeptin Neurons in Rats", "chroma:document": "innovation, Grant JPMJFS2120 to S.H. The RIA was performed at the Nagoya University Radioisotope Research\nCenter. We thank the National Hormone and Peptide Program for the rat LH assay kit; and Dr. Jeremy Allen\n(Edanz Group; https://en-author-services.edanz.com) and Dr. Nicola Skoulding for editing a draft of this\nmanuscript.\n*N.I. and S.H. contributed equally to this work as co-first authors.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Naoko Inoue at ninoue@agr.nagoya-u.ac.jp.\nhttps://doi.org/10.1523/JNEUROSCI.1496-22.2023\nCopyright \u00a9 2023 Inoue, Hazim et al.\nThis is an open-access article distributed under the terms of the Creative Commons Attribution 4.0\nInternational license, which permits unrestricted use, distribution and reproduction in any medium provided\nthat the original work is properly attributed.\n2140 \u2022 The Journal of Neuroscience, March 22, 2023 \u2022 43(12):2140\u20132152"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1261
encoding: FLOAT32
metadata:
{"title": "Macrophages Promote Repair of Inner Hair Cell Ribbon Synapses following Noise-Induced Cochlear Synaptopathy", "chroma:document": "Development/Plasticity/Repair\nMacrophages Promote Repair of Inner Hair Cell Ribbon\nSynapses following Noise-Induced Cochlear Synaptopathy\nVijayprakash Manickam,1 Dinesh Y. Gawande,1 Andrew R. Stothert,1 Anna C. Clayman,2 Lyudmila Batalkina,1\nMark E. Warchol,2 Kevin K. Ohlemiller,2 and Tejbeer Kaur1\n1Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, Nebraska 68178, and 2Department of Otolaryngology,\nSchool of Medicine, Washington University, St. Louis, Missouri 63110\nResident cochlear macrophages rapidly migrate into the inner hair cell synaptic region and directly contact the damaged synaptic con-\nnections after noise-induced synaptopathy. Eventually, such damaged synapses are spontaneously repaired, but the precise role of mac-\nrophages in synaptic degeneration and repair remains unknown. To address this, cochlear macrophages were eliminated using colony\nstimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Sustained treatment with PLX5622 in CX3CR1GFP/1 mice of both sexes led\nto robust elimination of resident macrophages (;94%) without significant adverse effects on peripheral leukocytes, cochlear function,\nand structure. At 1 day (d) post noise exposure of 93 or 90dB SPL for 2 hours, the degree of hearing loss and synapse loss were\ncomparable in the presence and absence of macrophages. At 30d after exposure, damaged synapses appeared repaired in the presence\nof macrophages. However, in the absence of macrophages, such synaptic repair was significantly reduced. Remarkably, on cessation of\nPLX5622 treatment, macrophages repopulated the cochlea, leading to enhanced synaptic repair. Elevated auditory brainstem response\nthresholds and reduced auditory brainstem response Peak 1 amplitudes showed limited recovery in the absence of macrophages but\nrecovered similarly with resident and repopulated macrophages. Cochlear neuron loss was augmented in the absence of macrophages"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1262
encoding: FLOAT32
metadata:
{"title": "Macrophages Promote Repair of Inner Hair Cell Ribbon Synapses following Noise-Induced Cochlear Synaptopathy", "chroma:document": "but showed preservation with resident and repopulated macrophages after noise exposure. While the central auditory effects of\nPLX5622 treatment and microglia depletion remain to be investigated, these data demonstrate that macrophages do not affect synap-\ntic degeneration but are necessary and sufficient to restore cochlear synapses and function after noise-induced synaptopathy.\nKey words: cochlea; inner hair cells; macrophages; noise-induced hearing loss; PLX5622; ribbon synapses\nSignificance Statement\nThe synaptic connections between cochlear inner hair cells and spiral ganglion neurons can be lost because of noise over expo-\nsure or biological aging. This loss may represent the most common causes of sensorineural hearing loss also known as hidden\nhearing loss. Synaptic loss results in degradation of auditory information, leading to difficulty in listening in noisy environ-\nments and other auditory perceptual disorders. We demonstrate that resident macrophages of the cochlea are necessary and\nsufficient to restore synapses and function following synaptopathic noise exposure. Our work reveals a novel role for innate-\nimmune cells, such as macrophages in synaptic repair, that could be harnessed to regenerate lost ribbon synapses in noise- or\nage-linked cochlear synaptopathy, hidden hearing loss, and associated perceptual anomalies.\nIntroduction\nSensorineural hearing loss reflects damage to the sensory recep-\ntors (i.e., hair cells and/or spiral ganglion neurons [SGNs]) or to\nthe ribbon synapses between inner hair cells (IHCs) and SGNs.\nNoise trauma is the most common preventable cause of hearing\nloss. It has been suggested that at least 10 million adults (6%) in\nthe United States under age 70, and perhaps as many as 40 mil-\nlion adults (24%), have features of hearing loss from exposure to\nloud noise; and 12% or more of the world population is at risk\nfor noise-induced loss of hearing (Le et al., 2017; Sliwinska-\nKowalska and Zaborowski, 2017; GBD 2019 Hearing Loss"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1263
encoding: FLOAT32
metadata:
{"title": "Macrophages Promote Repair of Inner Hair Cell Ribbon Synapses following Noise-Induced Cochlear Synaptopathy", "chroma:document": "Collaborators, 2021; World Health Organization, 2021).\nResearch in rodents and primate models and in humans has\nshown that IHC ribbon synapses are vulnerable to rapid and\nReceived June 26, 2022; revised Feb. 7, 2023; accepted Feb. 10, 2023.\nAuthor contributions: V.M., D.Y.G., A.R.S., and T.K. designed research; V.M., D.Y.G., A.R.S., A.C.C., L.B., and\nT.K. performed research; V.M., D.Y.G., A.R.S., A.C.C., and T.K. analyzed data; V.M., M.E.W., K.K.O., and T.K.\nwrote the first draft of the paper; V.M., M.E.W., K.K.O., and T.K. edited the paper.\nThis work was supported by National Institute on Deafness and Other Communication Disorders Grants R03\nDC015320 and R01 DC019918, Nebraska State Funds, and Bellucci Translational Hearing Research Funds to\nT.K. This work was also supported by the Translational Hearing Center at Creighton University, Boys Town\nNational Research Hospital, and University of Nebraska Medical Center with CoBRE Award GM139762 from the\nNational Institute of General Medical Science, a component of the National Institutes of Health. This\ninvestigation is solely the responsibility of the authors and does not necessarily represent the official views of\nany supporting institution. We thank Sharon Kujawa (Massachusetts Eye and Ear) and the Translational\nHearing Research Group, Creighton University, Omaha, Nebraska for constructive criticism that tremendously\nimproved the manuscript.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Tejbeer Kaur at TejbeerKaur@creighton.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1273-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, March 22, 2023 \u2022 43(12):2075\u20132089 \u2022 2075"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1264
encoding: FLOAT32
metadata:
{"title": "The Basolateral Amygdala Sends a Mixed (GABAergic and Glutamatergic) Projection to the Mediodorsal Thalamic Nucleus", "chroma:document": "Systems/Circuits\nThe Basolateral Amygdala Sends a Mixed (GABAergic and\nGlutamatergic) Projection to the Mediodorsal Thalamic\nNucleus\nNowrin Ahmed and Denis Par\u00e9\nCenter for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102\nThe medial prefrontal cortex receives converging inputs from the mediodorsal thalamic nucleus (MD) and basolateral amyg-\ndala (BLA). Although many studies reported that the BLA also projects to MD, there is conflicting evidence regarding this\nprojection, with some data suggesting that it originates from GABAergic or glutamatergic neurons. Therefore, the present\nstudy aimed to determine the neurotransmitter used by MD-projecting BLA cells in male and female rats. We first examined\nwhether BLA cells retrogradely labeled by Fast Blue infusions in MD are immunopositive for multiple established markers of\nBLA interneurons. A minority of MD-projecting BLA cells expressed somatostatin (;22%) or calretinin (;11%) but not\nother interneuronal markers, suggesting that BLA neurons projecting to MD not only include glutamatergic cells, but also\nlong-range GABAergic neurons. Second, we examined the responses of MD cells to optogenetic activation of BLA axons using\nwhole-cell recordings in vitro. Consistent with our immunohistochemical findings, among responsive MD cells, light stimuli\ntypically elicited isolated EPSPs (73%) or IPSPs (27%) as well as coincident EPSPs and IPSPs (11%). Indicating that these\nIPSPs were monosynaptic, light-evoked EPSPs and IPSPs had the same latency and the IPSPs persisted in the presence of\nionotropic glutamate receptor antagonists. Overall, our results indicate that the BLA sends a mixed, glutamatergic-GABAergic\nprojection to MD, which likely influences coordination of activity between BLA, MD, and medial prefrontal cortex. An impor-\ntant challenge for future studies will be to examine the connections formed by MD-projecting glutamatergic and GABAergic\nBLA cells with each other and other populations of BLA cells."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1265
encoding: FLOAT32
metadata:
{"title": "The Basolateral Amygdala Sends a Mixed (GABAergic and Glutamatergic) Projection to the Mediodorsal Thalamic Nucleus", "chroma:document": "Key words: amygdala; basolateral; mediodorsal; optogenetics; prefrontal; thalamus\nSignificance Statement\nThe mediodorsal thalamic nucleus (MD) and basolateral amygdala (BLA) send convergent projections to the medial prefron-\ntal cortex. Although many studies reported that the BLA also projects to MD, there is conflicting evidence as to whether this\nprojection is glutamatergic or GABAergic. By combining tract tracing, immunohistochemistry, optogenetics, and patch clamp\nrecordings in vitro, we found that BLA neurons projecting to MD not only include glutamatergic cells, but also long-range\nGABAergic neurons. Differential recruitment of these two contingents of cells likely influences coordination of activity\nbetween the BLA, MD, and medial prefrontal cortex.\nIntroduction\nAlthough the basolateral complex of the amygdala (BLA) is often\nlikened to the cerebral cortex (Carlsen and Heimer, 1988), some\nof its features are inconsistent with this analogy. Reminiscent of\ncortex, the BLA contains a similar complement of cell types, includ-\ning a majority of spiny glutamatergic projection cells and a hetero-\ngeneous group of aspiny inhibitory interneurons (McDonald, 1992;\nSmith and Par\u00e9, 1994; Mascagni and McDonald, 2007; Spampanato\net al., 2011; Capogna, 2014; Vereczki et al., 2021). Also, as in cortex\nwhere inter-related areas tend to project to the same striatal territo-\nries (Alexander et al., 1986), the BLA innervates cortical areas that\ntarget the same regions of the striatum as it does (Groenewegen et\nal., 1990; McDonald, 1991).\nHowever, the analogy breaks down when considering BLA\u2019s\nthalamic connections. Unlike the generally reciprocal connec-\ntions between the dorsal thalamus and cortex (Jones, 2007), most\ndorsal thalamic nuclei projecting to the BLA receive little or no\nreturn afferents. Indeed, the BLA receives heavy inputs from\nparts of the ventroposterior and medial geniculate nuclei as well\nReceived Oct. 11, 2022; revised Dec. 13, 2022; accepted Dec. 20, 2022."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1266
encoding: FLOAT32
metadata:
{"title": "The Basolateral Amygdala Sends a Mixed (GABAergic and Glutamatergic) Projection to the Mediodorsal Thalamic Nucleus", "chroma:document": "Author contributions: N.A. and D.P. designed research; N.A. performed research; N.A. and D.P. analyzed\ndata; N.A. and D.P. edited the paper; D.P. wrote the first draft of the paper; D.P. wrote the paper.\nThis work was supported by the National Institutes of Health National Institute of Mental Health Grant R01\nMH-107239 (to D.P.). N.A. was supported by the Behavioral and Neural Sciences Graduate Program of Rutgers\nUniversity.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Denis Par\u00e9 at pare@rutgers.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1924-22.2022\nCopyright \u00a9 2023 the authors\n2104 \u2022 The Journal of Neuroscience, March 22, 2023 \u2022 43(12):2104\u20132115"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1267
encoding: FLOAT32
metadata:
{"title": "Sensory and Choice Responses in MT Distinct from Motion Encoding", "chroma:document": "Systems/Circuits\nSensory and Choice Responses in MT Distinct from Motion\nEncoding\nAaron J. Levi,1p\nYuan Zhao,2p\nIl Memming Park,2 and Alexander C. Huk1,3\n1Center for Perceptual Systems, Departments of Neuroscience and Psychology, The University of Texas at Austin, Austin, Texas 78705,\n2Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York 11794, and 3Fuster Laboratory, University of\nCalifornia Los Angeles, Los Angeles CA 90095\nThe macaque middle temporal (MT) area is well known for its visual motion selectivity and relevance to motion perception,\nbut the possibility of it also reflecting higher-level cognitive functions has largely been ignored. We tested for effects of task\nperformance distinct from sensory encoding by manipulating subjects\u2019 temporal evidence-weighting strategy during a direc-\ntion discrimination task while performing electrophysiological recordings from groups of MT neurons in rhesus macaques\n(one male, one female). This revealed multiple components of MT responses that were, surprisingly, not interpretable as behaviorally\nrelevant modulations of motion encoding, or as bottom-up consequences of the readout of motion direction from MT. The time-vary-\ning motion-driven responses of MT were strongly affected by our strategic manipulation\u2014but with time courses opposite the subjects\u2019\ntemporal weighting strategies. Furthermore, large choice-correlated signals were represented in population activity distinct from its\nmotion responses, with multiple phases that lagged psychophysical readout and even continued after the stimulus (but which preceded\nmotor responses). In summary, a novel experimental manipulation of strategy allowed us to control the time course of readout to\nchallenge the correlation between sensory responses and choices, and population-level analyses of simultaneously recorded ensembles\nallowed us to identify strong signals that were so distinct from direction encoding that conventional, single-neuron-centric analyses"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1268
encoding: FLOAT32
metadata:
{"title": "Sensory and Choice Responses in MT Distinct from Motion Encoding", "chroma:document": "could not have revealed or properly characterized them. Together, these approaches revealed multiple cognitive contributions to MT\nresponses that are task related but not functionally relevant to encoding or decoding of motion for psychophysical direction discrimi-\nnation, providing a new perspective on the assumed status of MT as a simple sensory area.\nKey words: choice-related activity; decision-making; population decoding; temporal weighting; visual motion\nSignificance Statement\nThis study extends understanding of the middle temporal (MT) area beyond its representation of visual motion. Combining\nmultineuron recordings, population-level analyses, and controlled manipulation of task strategy, we exposed signals that\ndepended on changes in temporal weighting strategy, but did not manifest as feedforward effects on behavior. This was dem-\nonstrated by (1) an inverse relationship between temporal dynamics of behavioral readout and sensory encoding, (2) a\nchoice-correlated signal that always lagged the stimulus time points most correlated with decisions, and (3) a distinct choice-\ncorrelated signal after the stimulus. These findings invite re-evaluation of MT for functions outside of its established sensory\nrole and highlight the power of experimenter-controlled changes in temporal strategy, coupled with recording and analysis\napproaches that transcend the single-neuron perspective.\nIntroduction\nPrimate middle temporal (MT) area plays a critical role in the\nperception of visual motion. A long line of study has established\nthat MT\u2019s encoding of motion direction is quantitatively consist-\nent with perceptual sensitivity, that noise in its responses is cor-\nrelated with behavioral variability, and that causal perturbations\nof its activity affect motion perception in lawful and substantial\nways (Newsome and Par\u00e9, 1988; Britten et al., 1992; Salzman et\nal., 1992; Britten et al., 1996). Owing to this powerfully integrated\nset of findings, many models and experiments have been able to"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1269
encoding: FLOAT32
metadata:
{"title": "Sensory and Choice Responses in MT Distinct from Motion Encoding", "chroma:document": "assume that MT is the key place that the brain looks to for infor-\nmation about visual motion. However, these successes do not\nReceived Feb. 6, 2022; revised Jan. 16, 2023; accepted Jan. 19, 2023.\nAuthor contributions: A.J.L. and A.C.H. designed research; A.J.L. performed research; A.J.L., Y.Z., and I.M.P.\nanalyzed data; A.J.L. and A.C.H. wrote the paper.\nI.M.P and A.C.H. were supported by National Science Fondation Grant IIS-1734910. A.J.L. was supported by\nNational Institutes of Health/National Eye Institute Grant R01-EY-017366. We thank A. Laudano for animal\nsupport, C. Badillo for technical support, as well as J. Yates and L. Katz for helpful advice and discussion.\n*A.J.L. and Y.Z. contributed equally to this work.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Aaron J. Levi at alevi813@gmail.com or Alexander C. Huk at\nalexhuk@ucla.edu.\nhttps://doi.org/10.1523/JNEUROSCI.0267-22.2023\nCopyright \u00a9 2023 Levi, Zhao et al.\nThis is an open-access article distributed under the terms of the Creative Commons Attribution 4.0\nInternational license, which permits unrestricted use, distribution and reproduction in any medium provided\nthat the original work is properly attributed.\n2090 \u2022 The Journal of Neuroscience, March 22, 2023 \u2022 43(12):2090\u20132103"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1270
encoding: FLOAT32
metadata:
{"title": "The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning", "chroma:document": "Behavioral/Cognitive\nThe Human Centromedial Amygdala Contributes to\nNegative Prediction Error Signaling during Appetitive and\nAversive Pavlovian Gustatory Learning\nEmilia Kolada,1 Krzysztof Bielski,1 Mateusz Wilk,1 Krystyna Rymarczyk,2 Piotr Bogorodzki,3 Pawe\u0142 Kazulo,3\nBartosz Kossowski,4 Marek Wypych,4 Artur Marchewka,4 Leszek Kaczmarek,5\nEwelina Knapska,1\nand\nIwona Szatkowska1\n1Neurobiology of Emotions Laboratory, Centre of Excellence for Neural Plasticity and Brain Disorders (BrainCity), Nencki Institute of Experimental\nBiology, Polish Academy of Sciences, 02-093 Warsaw, Poland, 2Behavioral Neuroscience Laboratory, Department of Biological Psychology, SWPS\nUniversity, 03-815 Warsaw, Poland, 3Institute of Radioelectronics and Multimedia Technology, Warsaw University of Technology, 00-665 Warsaw,\nPoland, 4Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland, and\n5Laboratory of Neurobiology, Centre of Excellence for Neural Plasticity and Brain Disorders (BrainCity), Nencki Institute of Experimental Biology,\nPolish Academy of Sciences, Warsaw, 02-093, Poland\nPrediction error (PE) is the mismatch between a prior expectation and reality, and it lies at the core of associative\nlearning about aversive and appetitive stimuli. Human studies on fear learning have linked the amygdala to aversive\nPEs. In contrast, the relationship between the amygdala and PE in appetitive settings and stimuli, unlike those that\ninduce fear, has received less research attention. Animal studies show that the amygdala is a functionally heterogene-\nous structure. Nevertheless, the role of the amygdala nuclei in PE signaling remains unknown in humans. To clarify\nthe role of two subdivisions of the human amygdala, the centromedial amygdala (CMA) and basolateral amygdala\n(BLA), in appetitive and aversive PE signaling, we used gustatory pavlovian learning involving eating-related natural-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1271
encoding: FLOAT32
metadata:
{"title": "The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning", "chroma:document": "istic outcomes. Thirty-eight right-handed individuals (19 females) participated in the study. We found that surprise\nwith neutral feedback when a reward is expected triggers activity within the left and right CMA. When an aversive\noutcome is expected, surprise with neutral feedback triggers activity only within the left CMA. Notably, the BLA was\nnot activated by those conditions. Thus, the CMA engages in negative PE signaling during appetitive and aversive gus-\ntatory pavlovian learning, whereas the BLA is not critical for this process. In addition, PE-related activity within the\nleft CMA during aversive learning is negatively correlated with neuroticism and positively correlated with extraver-\nsion. The findings indicate the importance of the CMA in gustatory learning when the value of outcomes changes and\nhave implications for understanding psychological conditions that manifest perturbed processing of negative PEs.\nKey words: centromedial amygdala; extraversion; gustatory learning; neuroticism; pavlovian learning; prediction error\nSignificance Statement\nA discrepancy between a prediction and an actual outcome (PE) plays a crucial role in learning. Learning improves when an\noutcome is more significant than expected (positive PE) and worsens when it is smaller than expected (negative PE). We\nfound that the negative PE during appetitive and aversive taste learning is associated with increased activity of the CMA,\nwhich suggests that the CMA controls taste learning. Our findings may have implications for understanding psychological\nstates associated with deficient learning from negative PEs, such as obesity and addictive behaviors.\nReceived May 13, 2022; revised Mar. 6, 2023; accepted Mar. 13, 2023.\nAuthor contributions: E. Kolada, A.M., L.K., E. Knapska, and I.S. designed research; E. Kolada, K.B., K.R., B.K., and I.S.\nperformed research; E. Kolada, K.B., M. Wilk, P.B., P.K., and M. Wypych analyzed data; E. Kolada, E. Knapska, and\nI.S. wrote the paper."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1272
encoding: FLOAT32
metadata:
{"title": "The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning", "chroma:document": "This work was supported by National Science Center (Poland) Grant 2014/15/B/HS6/03658) to I.S. and BrainCity\nCenter of Excellence for Neural Plasticity and Brain Disorders Grant MAB 2 to E. Kolada, K.B., L.K., and E. Knapska.\nK. Bielski\u2019s present address: Institute of Psychology, Jagiellonian University, 30-060 Cracow, Poland.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Emilia Kolada at e.kolada@nencki.edu.pl or Iwona Szatkowska at\ni.szatkowska@nencki.edu.pl.\nhttps://doi.org/10.1523/JNEUROSCI.0926-22.2023\nCopyright \u00a9 2023 Kolada et al.\nThis is an open-access article distributed under the terms of the Creative Commons Attribution 4.0\nInternational license, which permits unrestricted use, distribution and reproduction in any medium provided\nthat the original work is properly attributed.\n3176 \u2022 The Journal of Neuroscience, April 26, 2023 \u2022 43(17):3176\u20133185"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1273
encoding: FLOAT32
metadata:
{"title": "Concurrent- and After-Effects of Medial Temporal Lobe Stimulation on Directed Information Flow to and from Prefrontal and Parietal Cortices during Memory Formation", "chroma:document": "Behavioral/Cognitive\nConcurrent- and After-Effects of Medial Temporal Lobe\nStimulation on Directed Information Flow to and from\nPrefrontal and Parietal Cortices during Memory Formation\nAnup Das1 and Vinod Menon1,2,3\n1Department of Psychiatry & Behavioral Sciences, 2Department of Neurology & Neurological Sciences, and 3Stanford Neurosciences Institute,\nStanford University School of Medicine, Stanford, California 94305\nElectrical stimulation of the medial temporal lobe (MTL) has the potential to uncover causal circuit mechanisms underlying\nmemory function. However, little is known about how MTL stimulation alters information flow with frontoparietal cortical\nregions implicated in episodic memory. We used intracranial EEG recordings from humans (14 participants, 10 females) to\ninvestigate how MTL stimulation alters directed information flow between MTL and PFC and between MTL and posterior pa-\nrietal cortex (PPC). Participants performed a verbal episodic memory task during which they were presented with words and\nasked to recall them after a delay of ;20 s; 50 Hz stimulation was applied to MTL electrodes on selected trials during mem-\nory encoding. Directed information flow was examined using phase transfer entropy. Behaviorally, we observed that MTL\nstimulation reduced memory recall. MTL stimulation decreased top-down PFC\ufb01MTL directed information flow during\nboth memory encoding and subsequent memory recall, revealing aftereffects more than 20 s after end of stimulation.\nStimulation suppressed top-down PFC\ufb01MTL influences to a greater extent than PPC\ufb01MTL. Finally, MTL\ufb01PFC informa-\ntion flow on stimulation trials was significantly lower for successful, compared with unsuccessful, memory recall; in con-\ntrast, MTL\ufb01ventral PPC information flow was higher for successful, compared with unsuccessful, memory recall.\nTogether, these results demonstrate that the effects of MTL stimulation are behaviorally, regionally, and directionally spe-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1274
encoding: FLOAT32
metadata:
{"title": "Concurrent- and After-Effects of Medial Temporal Lobe Stimulation on Directed Information Flow to and from Prefrontal and Parietal Cortices during Memory Formation", "chroma:document": "cific, that MTL stimulation selectively impairs directional signaling with PFC, and that causal MTL-ventral PPC circuits\nsupport successful memory recall. Findings provide new insights into dynamic casual circuits underling episodic memory\nand their modulation by MTL stimulation.\nKey words: causal circuits in episodic memory; deep brain stimulation; directed information flow; human intracranial\nEEG; medial temporal lobe; prefrontal and parietal cortices\nSignificance Statement\nThe medial temporal lobe (MTL) and its interactions with prefrontal and parietal cortices (PFC and PPC) play a critical role in\nhuman memory. Dysfunctional MTL-PFC and MTL-PPC circuits are prominent in psychiatric and neurologic disorders, includ-\ning Alzheimer\u2019s disease and schizophrenia. Brain stimulation has emerged as a potential mechanism for enhancing memory and\ncognitive functions, but the underlying neurophysiological mechanisms and dynamic causal circuitry underlying bottom-up and\ntop-down signaling involving the MTL are unknown. Here, we use intracranial EEG recordings to investigate the effects of MTL\nstimulation on causal signaling in key episodic memory circuits linking the MTL with PFC and PPC. Our findings have implica-\ntions for translational applications aimed at realizing the promise of brain stimulation-based treatment of memory disorders.\nIntroduction\nThe medial temporal lobe (MTL) and its interactions with pre-\nfrontal cortex (PFC) play a foundational role in human memory\n(Vogt and Pandya, 1987; Wagner et al., 2005; Curtis, 2006;\nHusain and Nachev, 2007; Cabeza et al., 2008; Eichenbaum,\n2017; Rolls, 2018, 2019; Rutishauser et al., 2021; Amer and\nDavachi, 2022). Dysfunctional MTL-PFC circuits are prominent\nin psychiatric and neurologic disorders, including Alzheimer\u2019s\ndisease and schizophrenia (Meyer-Lindenberg et al., 2005;\nDickerson and Eichenbaum, 2010; Uhlhaas and Singer, 2012).\nReceived Sep. 10, 2022; revised Mar. 6, 2023; accepted Mar. 13, 2023."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1275
encoding: FLOAT32
metadata:
{"title": "Concurrent- and After-Effects of Medial Temporal Lobe Stimulation on Directed Information Flow to and from Prefrontal and Parietal Cortices during Memory Formation", "chroma:document": "Author contributions: A.D. and V.M. designed research; A.D. and V.M. performed research; A.D. analyzed\ndata; A.D. wrote the first draft of the paper; A.D. and V.M. edited the paper; A.D. and V.M. wrote the paper.\nThis work was supported by National Institutes of Health Grants NS086085 and EB022907. We thank Dr.\nYuan Zhang for assistance with statistical analysis.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Anup Das at a1das@stanford.edu or Vinod Menon at\nmenon@stanford.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1728-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, April 26, 2023 \u2022 43(17):3159\u20133175 \u2022 3159"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1276
encoding: FLOAT32
metadata:
{"title": "Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing", "chroma:document": "Systems/Circuits\nSubgenual and Hippocampal Pathways in Amygdala Are Set\nto Balance Affect and Context Processing\nMary Kate P. Joyce,1,2\nJingyi Wang,1 and\nHelen Barbas1,2,3\n1Neural Systems Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts 022152, 2Graduate Program in\nNeuroscience, Boston University and School of Medicine, Boston, Massachusetts 02118, and 3Department of Anatomy and Neurobiology, Boston\nUniversity School of Medicine, Boston, Massachusetts 02118\nThe amygdala, hippocampus, and subgenual cortex area 25 (A25) are engaged in complex cognitive-emotional processes. Yet\npathway interactions from hippocampus and A25 with postsynaptic sites in amygdala remain largely unknown. In rhesus\nmonkeys of both sexes, we studied with neural tracers how pathways from A25 and hippocampus interface with excitatory\nand inhibitory microcircuits in amygdala at multiple scales. We found that both hippocampus and A25 innervate distinct as\nwell as overlapping sites of the basolateral (BL) amygdalar nucleus. Unique hippocampal pathways heavily innervated the\nintrinsic paralaminar basolateral nucleus, which is associated with plasticity. In contrast, orbital A25 preferentially innervated\nanother intrinsic network, the intercalated masses, an inhibitory reticulum that gates amygdalar autonomic output and inhib-\nits fear-related behaviors. Finally, using high-resolution confocal and electron microscopy (EM), we found that among inhibi-\ntory postsynaptic targets in BL, both hippocampal and A25 pathways preferentially formed synapses with calretinin (CR)\nneurons, which are known for disinhibition and may enhance excitatory drive in the amygdala. Among other inhibitory post-\nsynaptic sites, A25 pathways innervated the powerful parvalbumin (PV) neurons which may flexibly regulate the gain of neu-\nronal assemblies in the BL that affect the internal state. In contrast, hippocampal pathways innervated calbindin (CB)"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1277
encoding: FLOAT32
metadata:
{"title": "Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing", "chroma:document": "inhibitory neurons, which modulate specific excitatory inputs for processing context and learning correct associations.\nCommon and unique patterns of innervation in amygdala by hippocampus and A25 have implications for how complex cog-\nnitive and emotional processes may be selectively disrupted in psychiatric disorders.\nKey words: emotional regulation; fear conditioning; inhibitory neurons; neural circuits; nonhuman primate; ventrome-\ndial prefrontal cortex\nSignificance Statement\nThe hippocampus, subgenual A25, and amygdala are associated with learning, memory, and emotions. We found that A25 is\npoised to affect diverse amygdalar processes, from emotional expression to fear learning by innervating the basal complex\nand the intrinsic intercalated masses. Hippocampal pathways uniquely interacted with another intrinsic amygdalar nucleus\nwhich is associated with plasticity, suggesting flexible processing of signals in context for learning. In the basolateral (BL)\namygdala, which has a role in fear learning, both hippocampal and A25 interacted preferentially with disinhibitory neurons,\nsuggesting a boost in excitation. The two pathways diverged in innervating other classes of inhibitory neurons, suggesting cir-\ncuit specificities that could become perturbed in psychiatric diseases.\nIntroduction\nThe amygdala, hippocampus, and subgenual cingulate area\n25 (A25) of the medial prefrontal cortex (mPFC) are essen-\ntial for processes associated with emotion, memory, and in-\nternal states, and disruption of these nodes can precipitate\npsychiatric disturbances in humans (for review, see Hiser\nand Koenigs, 2018; Gray et al., 2020; Kaul et al., 2021).\nUnderstanding the organization of these circuits in nonhu-\nman primates remains an urgent goal, as novel and safe\ntherapies for mood disorders have proven difficult to trans-\nlate from rodent models, although remarkable strides have\nbeen made (Roberts, 2020).\nReceived Nov. 5, 2022; revised Mar. 2, 2023; accepted Mar. 13, 2023."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1278
encoding: FLOAT32
metadata:
{"title": "Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing", "chroma:document": "Author contributions: M.K.P.J., J.W., and H.B. designed research; M.K.P.J. and J.W. performed research;\nM.K.P.J., J.W., and H.B. analyzed data; M.K.P.J. wrote the first draft of the paper; M.K.P.J., J.W., and H.B.\nedited the paper; M.K.P.J., J.W., and H.B. wrote the paper.\nThis work was supported by National Institutes of Health Grants R01MH057414 and R01MH117785 (to H.B.).\nWe thank Jess Holz, MFA for electron microscopy and technical assistance.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Helen Barbas at barbas@bu.edu.\nhttps://doi.org/10.1523/JNEUROSCI.2066-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, April 26, 2023 \u2022 43(17):3061\u20133080 \u2022 3061"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1279
encoding: FLOAT32
metadata:
{"title": "Pharmacological Inactivation of the Bed Nucleus of the Stria Terminalis Increases Affiliative Social Behavior in Rhesus Macaques", "chroma:document": "Behavioral/Cognitive\nPharmacological Inactivation of the Bed Nucleus of the Stria\nTerminalis Increases Affiliative Social Behavior in Rhesus\nMacaques\nJessica T. Jacobs,1,2\nRafael S. Maior,2,3 Hannah F. Waguespack,1,2 Carolina Campos-Rodriguez,2\nPatrick A. Forcelli,1,2,4p and Ludise Malkova1,2p\n1Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, 20057, 2Department of Pharmacology & Physiology, Georgetown\nUniversity, Washington, DC, 20057, 3Laboratory of Neurosciences, Metabolism and Behavior, Department of Physiological Sciences, Institute of\nBiology, University of Brasilia, 70910-900, Brasilia, Brazil, and 4Department of Neuroscience, Georgetown University, Washington, DC 20057\nThe bed nucleus of the stria terminalis (BNST) has been implicated in a variety of social behaviors, including aggression,\nmaternal care, mating behavior, and social interaction. Limited evidence from rodent studies suggests that activation of the\nBNST results in a decrease in social interaction between unfamiliar animals. The role of the BNST in social interaction in pri-\nmates remains wholly unexamined. Nonhuman primates provide a valuable model for studying social behavior because of\nboth their rich social repertoire and neural substrates of behavior with high translational relevance to humans. To test the\nhypothesis that the primate BNST is a critical modulator of social behavior, we performed intracerebral microinfusions of the\nGABAA agonist muscimol to transiently inactivate the BNST in male macaque monkeys. We measured changes in social inter-\naction with a familiar same-sex conspecific. Inactivation of the BNST resulted in significant increase in total social contact.\nThis effect was associated with an increase in passive contact and a significant decrease in locomotion. Other nonsocial\nbehaviors (sitting passively alone, self-directed behaviors, and manipulation) were not impacted by BNST inactivation. As"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1280
encoding: FLOAT32
metadata:
{"title": "Pharmacological Inactivation of the Bed Nucleus of the Stria Terminalis Increases Affiliative Social Behavior in Rhesus Macaques", "chroma:document": "part of the \u201cextended amygdala,\u201d the BNST is highly interconnected with the basolateral (BLA) and central (CeA) nuclei of\nthe amygdala, both of which also play critical roles in regulating social interaction. The precise pattern of behavioral changes\nwe observed following inactivation of the BNST partially overlaps with our prior reports in the BLA and CeA. Together, these\ndata demonstrate that the BNST is part of a network regulating social behavior in primates.\nKey words: amygdala; BNST; macaque; muscimol; primate\nSignificance Statement\nThe bed nucleus of the stria terminalis (BNST) has a well-established role in anxiety behaviors, but its role in social behavior\nis poorly understood. No prior studies have evaluated the impact of BNST manipulations on social behavior in primates. We\nfound that transient pharmacological inactivation of the BNST increased social behavior in pairs of macaque monkeys. These\ndata suggest the BNST contributes to the brain networks regulating sociability.\nIntroduction\nThe bed nucleus of the stria terminalis (BNST) is a subcortical\nstructure located in the ventral forebrain. It has been described\nas a component of the \u201cextended amygdala\u201d because of its ana-\ntomic and functional similarities to the amygdaloid complex\n(Alheid and Heimer, 1988; Alheid et al., 1998; Fox et al., 2015).\nThe BNST is densely and reciprocally interconnected with key\nlimbic structures, including the amygdala and the hypothalamus\n(Silverman et al., 1981; Weller and Smith, 1982; Dong et al.,\n2001a; Dong and Swanson, 2004; deCampo and Fudge, 2013;\nKim et al., 2013; Torrisi et al., 2015; Fudge et al., 2017; Huang et\nal., 2021) and has been implicated in a range of behavioral func-\ntions, including the stress response, extended-duration fear states\n(i.e., anxiety), and social behavior (Walker et al., 2003; Lebow\nand Chen, 2016; Lischinsky and Lin, 2020; Flanigan and Kash,\n2022).\nThe BNST, and its contributions to social behavior, has been\nmost extensively studied in rodent models. In both rats and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1281
encoding: FLOAT32
metadata:
{"title": "Pharmacological Inactivation of the Bed Nucleus of the Stria Terminalis Increases Affiliative Social Behavior in Rhesus Macaques", "chroma:document": "Received Nov. 9, 2022; revised Feb. 6, 2023; accepted Feb. 27, 2023.\nAuthor contributions: J.T.J., P.A.F., and L.M. designed research; J.T.J., R.S.M., H.F.W., C.C.-R., P.A.F., and\nL.M. performed research; J.T.J., P.A.F., and L.M. analyzed data; J.T.J. wrote the first draft of the paper; J.T.J.,\nR.S.M., H.F.W., C.C.-R., P.A.F., and L.M. edited the paper.\nThis work was supported by the National Institute of Mental Health R01MH120638 to L.M. and P.A.F. RSM\nwas the recipient of a researcher fellowship from the Brazilian National Council for Scientific and\nTechnological Development (CNPq; 308291/2020-4).\n*P.A.F. and L.M. contributed equally to this work.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Ludise Malkova at malkoval@georgetown.edu or Patrick A. Forcelli\nat paf22@georgetown.edu.\nhttps://doi.org/10.1523/JNEUROSCI.2090-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, May 3, 2023 \u2022 43(18):3331\u20133338 \u2022 3331"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1282
encoding: FLOAT32
metadata:
{"title": "Beta Oscillations in Monkey Striatum Encode Reward Prediction Error Signals", "chroma:document": "Behavioral/Cognitive\nBeta Oscillations in Monkey Striatum Encode Reward\nPrediction Error Signals\nRuggero Basanisi,1\u0001 Kevin Marche,1,2\u0001 Etienne Combrisson,1\nPaul Apicella,1 \u0001\u0001 and\nAndrea Brovelli1 \u0001\u0001\n1Institut de Neurosciences de la Timone, Aix Marseille Universit\u00e9, Unit\u00e9 Mixte de Recherche 7289 Centre National de la Recherche Scientifique,\nMarseille 13005, France and 2Wellcome Center for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford,\nOxford OX3 9DU, United Kingdom\nReward prediction error (RPE) signals are crucial for reinforcement learning and decision-making as they quantify the mis-\nmatch between predicted and obtained rewards. RPE signals are encoded in the neural activity of multiple brain areas, such\nas midbrain dopaminergic neurons, prefrontal cortex, and striatum. However, it remains unclear how these signals are\nexpressed through anatomically and functionally distinct subregions of the striatum. In the current study, we examined to\nwhich extent RPE signals are represented across different striatal regions. To do so, we recorded local field potentials (LFPs)\nin sensorimotor, associative, and limbic striatal territories of two male rhesus monkeys performing a free-choice probabilistic\nlearning task. The trial-by-trial evolution of RPE during task performance was estimated using a reinforcement learning\nmodel fitted on monkeys\u2019 choice behavior. Overall, we found that changes in beta band oscillations (15\u201335 Hz), after the out-\ncome of the animal\u2019s choice, are consistent with RPE encoding. Moreover, we provide evidence that the signals related to\nRPE are more strongly represented in the ventral (limbic) than dorsal (sensorimotor and associative) part of the striatum. To\nconclude, our results suggest a relationship between striatal beta oscillations and the evaluation of outcomes based on RPE\nsignals and highlight a major contribution of the ventral striatum to the updating of learning processes.\nKey words: learning; LFP; mutual information; rewards; striatum"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1283
encoding: FLOAT32
metadata:
{"title": "Beta Oscillations in Monkey Striatum Encode Reward Prediction Error Signals", "chroma:document": "Significance Statement\nReward prediction error (RPE) signals are crucial for reinforcement learning and decision-making as they quantify the mismatch\nbetween predicted and obtained rewards. Current models suggest that RPE signals are encoded in the neural activity of multiple\nbrain areas, including the midbrain dopaminergic neurons, prefrontal cortex and striatum. However, it remains elusive whether\nRPEs recruit anatomically and functionally distinct subregions of the striatum. Our study provides evidence that RPE-related modu-\nlations in local field potential (LFP) power are dominant in the striatum. In particular, they are stronger in the rostro-ventral rather\nthan the caudo-dorsal striatum. Our findings contribute to a better understanding of the role of striatal territories in reward-based\nlearning and may be relevant for neuropsychiatric and neurologic diseases that affect striatal circuits.\nIntroduction\nThe striatum is the major component of the basal ganglia, and it\nplays a key role in reward-guided learning under the influence of\nascending dopaminergic projections from the ventral midbrain.\nIndeed, dopaminergic neurons are known to encode the differ-\nence between received and expected rewards, the so-called reward\nprediction error (RPE; Schultz, 2007, 2016a,b; Fujiyama et al.,\n2015), which is crucial for updating action values in reinforce-\nment learning models (Sutton and Barto, 1998). Previous neuro-\nphysiological studies on primates\u2019 and rodents\u2019 striatum have\nshown that subsets of output neurons (Roesch et al., 2009; Oyama\net al., 2010; Asaad and Eskandar, 2011) and putative interneurons\n(Apicella et al., 2009; Stalnaker et al., 2012) may carry RPE signals\nto promote reward-guided learning. Functional neuroimaging\nstudies in humans have also highlighted the role of the striatum\nin encoding RPEs (O\u2019Doherty, 2004, 2007; Bray and O\u2019Doherty,\n2007; Brovelli et al., 2008; Valentin and O\u2019Doherty, 2009; Park et\nReceived May 19, 2022; revised Feb. 22, 2023; accepted Mar. 17, 2023."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1284
encoding: FLOAT32
metadata:
{"title": "Beta Oscillations in Monkey Striatum Encode Reward Prediction Error Signals", "chroma:document": "Author contributions: K.M. and P.A. designed research; K.M. and P.A. performed research; R.B., K.M., E.C.,\nP.A., and A.B. contributed unpublished reagents/analytic tools; R.B. and A.B. analyzed data; R.B. and A.B.\nwrote the first draft of the paper; R.B., K.M., E.C., P.A., and A.B. edited the paper; R.B., K.M., P.A., and A.B.\nwrote the paper.\nR.B., E.C., and A.B. were supported by the Agence National de la Recherche Grant ANR-18-CE28-0016. R.B.\nwas supported by a PhD Scholarship awarded by the Neuroschool. E.C. was supported by the European\nUnion\u2019s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement\nNo. 945539 (Human Brain Project SGA3). P.A. and K.M. were supported by the Agence Nationale de la\nRecherche Grant ANR-11-BSV4-006. Support for K.M. was partially provided by Association Fran\u00e7aise du\nSyndrome de Gilles de la Tourette. The Center de Calcul Intensif of the Aix-Marseille University is\nacknowledged for granting access to its high-performance computing resources. We thank L. Renaud for\nassistance with monkey surgery and Dr. M. Esclapez for help with histology.\npR.B. and K.M. contributed equally to this work.\nppP.A. and A.B. are co-senior authors.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Andrea Brovelli at andrea.brovelli@univ-amu.fr or Ruggero\nBasanisi at ruggero.basanisi@gmail.com.\nhttps://doi.org/10.1523/JNEUROSCI.0952-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, May 3, 2023 \u2022 43(18):3339\u20133352 \u2022 3339"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1285
encoding: FLOAT32
metadata:
{"title": "3 ASO targeting RBM temperature-controlled poison in vivo exon splicing prevents neurodegeneration", "chroma:document": "Report\nASO targeting RBM3 temperature-controlled poison\nexon splicing prevents neurodegeneration in vivo\nMarco Preu\u00dfner1,*,\u2020\n, Heather L Smith2,3,\u2020, Daniel Hughes2,\u2021\n, Min Zhang1,\u2021,\nAnn-Kathrin Emmerichs1, Silvia Scalzitti1, Diego Peretti2, Dean Swinden2,3, Alexander Neumann1,4,\nTom Haltenhof1,4, Giovanna R Mallucci2,3,**\n& Florian Heyd1,***\nAbstract\nNeurodegenerative diseases are increasingly prevalent in the aging\npopulation, yet no disease-modifying treatments are currently\navailable. Increasing the expression of the cold-shock protein\nRBM3 through therapeutic hypothermia is remarkably neuropro-\ntective. However, systemic cooling poses a health risk, strongly\nlimiting its clinical application. Selective upregulation of RBM3 at\nnormothermia thus holds immense therapeutic potential. Here we\nidentify a poison exon within the RBM3 gene that is solely respon-\nsible for its cold-induced expression. Genetic removal or antisense\noligonucleotide (ASO)-mediated manipulation of this exon yields\nhigh RBM3 levels independent of cooling. Notably, a single admin-\nistration of ASO to exclude the poison exon, using FDA-approved\nchemistry, results in long-lasting increased RBM3 expression in\nmouse brains. In prion-diseased mice, this treatment leads to\nremarkable neuroprotection, with prevention of neuronal loss and\nspongiosis despite high levels of disease-associated prion protein.\nOur promising results in mice support the possibility that RBM3-\ninducing ASOs might also deliver neuroprotection in humans in\nconditions ranging from acute brain injury to Alzheimer\u2019s disease.\nKeywords alternative splicing coupled to nonsense-mediated decay;\nhypothermia; neurodegenerative diseases; neuroprotection; RBM3\nSubject Categories Genetics, Gene Therapy & Genetic Disease; Molecular\nBiology of Disease; Neuroscience\nDOI 10.15252/emmm.202217157 | Received 9 November 2022 |\nRevised 16 February 2023 | Accepted 18 February 2023 | Published online 22\nMarch 2023\nEMBO Mol Med (2023) 15: e17157\nIntroduction"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1286
encoding: FLOAT32
metadata:
{"title": "3 ASO targeting RBM temperature-controlled poison in vivo exon splicing prevents neurodegeneration", "chroma:document": "The expression of glycine-rich RNA-binding proteins upon cooling,\nsuch as CIRBP (Cold-induced RNA-binding protein) and RBM3\n(RNA-binding motif-3), was originally described in the 1990s (Danno\net al, 1997; Nishiyama et al, 1997). However, despite evolutionary\nconservation (Ciuzan et al, 2015) and extreme temperature sensitiv-\nity of this phenomenon (Jackson et al, 2015; Los et al, 2022), the\nmechanistic basis for cold-induced RBM3 expression has remained\nenigmatic. Our recent identification of temperature-regulated alter-\nnative splicing coupled to nonsense-mediated decay (NMD) provides\na global mechanism for the control of temperature-dependent gene\nexpression (Neumann et al, 2020). The NMD pathway recognizes\nmRNA isoforms containing premature termination codons (PTCs)\nand targets these mRNAs for degradation, thus allowing splicing-\ncontrolled\nregulation\nof\ngene\nexpression\n(Lykke-Andersen\n&\nJensen, 2015). NMD-inducing poison isoforms are frequently found\nin RNA-binding proteins (Neumann et al, 2020) and exclusion of a\npoison exon upon cooling in CIRBP provides an explanation for\ncold-induced expression (Haltenhof et al, 2020). While CIRBP has\ndiverse functions ranging from circadian sleep homeostasis to\ninflammation and cancer (Morf et al, 2012; Qiang et al, 2013; Lujan\net al, 2018; Hoekstra et al, 2019), the closely related RBM3 protein is\nstrongly associated with the neuroprotective effect of hypothermia.\nThis has been observed in scenarios ranging from in vitro protection\nfrom forced apoptosis of neuronal cell lines and brain slices (Chip\net al, 2011) to profound neuroprotective effects in vivo, where RBM3\ninduction by cooling or over-expression restores memory, prevents\nsynapse and neuronal loss, and extends survival in preclinical\nmouse models of prion and Alzheimer\u2019s disease (Peretti et al, 2015,\n2021). More recently, RBM3 has been shown to stimulate neurogen-\nesis in rodent brain after hypoxic\u2013ischemic brain injury (Zhu\net al, 2019) and to protect against neurotoxin effects in neuronal cell"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1287
encoding: FLOAT32
metadata:
{"title": "3 ASO targeting RBM temperature-controlled poison in vivo exon splicing prevents neurodegeneration", "chroma:document": "lines (Yang et al, 2019). Therapeutic hypothermia is used in some\n1 Institut f\u20acur Chemie und Biochemie, RNA Biochemie, Freie Universit\u20acat Berlin, Berlin, Germany\n2\nUK Dementia Research Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK\n3\nAltos Labs, Cambridge Institute of Science, Cambridge, UK\n4 Omiqa Bioinformatics, Berlin, Germany\n*Corresponding author. Tel: +49 30 838 70703; E-mail: mpreussner@zedat.fu-berlin.de\n**Corresponding author. Tel: +44 7766 924461; E-mail: gmallucci@altoslabs.com\n***Corresponding author. Tel: +49 30 838 62938; E-mail: florian.heyd@fu-berlin.de\n\u2020These authors contributed equally to this work\n\u2021These authors contributed equally to this work\n\u0001 2023 The Authors. Published under the terms of the CC BY 4.0 license.\nEMBO Molecular Medicine\n15: e17157 | 2023\n1 of 12"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1288
encoding: FLOAT32
metadata:
{"title": "Brain p3-Alcb peptide restores neuronal viability impaired by Alzheimer\u2019s amyloid b-peptide", "chroma:document": "Article\nBrain p3-Alcb peptide restores neuronal viability\nimpaired by Alzheimer\u2019s amyloid b-peptide\nSaori Hata1,2,\u2020, Haruka Saito1,3,\u2020, Takeharu Kakiuchi4, Dai Fukumoto4, Shigeyuki Yamamoto4\n,\nKensaku Kasuga5\n, Ayano Kimura1, Koichi Moteki1,3, Ruriko Abe3, Shungo Adachi6, Shoich Kinoshita1,3,\nKumiko Yoshizawa-Kumagaye7, Hideki Nishio7, Takashi Saito8,9\n, Takaomi C Saido8\n,\nTohru Yamamoto10\n, Masaki Nishimura11, Hidenori Taru1,3, Yuriko Sobu1,3, Hiroyuki Ohba4\n,\nShingo Nishiyama4, Norihiro Harada4\n, Takeshi Ikeuchi5\n, Hideo Tsukada4\n, Yasuomi Ouchi12,* &\nToshiharu Suzuki1,3,**\nAbstract\nWe propose a new therapeutic strategy for Alzheimer\u2019s disease\n(AD). Brain peptide p3-Alcb37 is generated from the neuronal pro-\ntein alcadein b through cleavage of c-secretase, similar to the gen-\neration of amyloid b (Ab) derived from Ab-protein precursor/APP.\nNeurotoxicity by Ab oligomers (Abo) is the prime cause prior to the\nloss of brain function in AD. We found that p3-Alcb37 and its\nshorter peptide p3-Alcb9-19 enhanced the mitochondrial activity\nof neurons and protected neurons against Abo-induced toxicity.\nThis is due to the suppression of the Abo-mediated excessive Ca2+\ninflux into neurons by p3-Alcb. Successful transfer of p3-Alcb9-19\ninto the brain following peripheral administration improved the\nmitochondrial viability in the brain of AD mice model, in which the\nmitochondrial activity is attenuated by increasing the neurotoxic\nhuman Ab42 burden, as revealed through brain PET imaging to\nmonitor mitochondrial function. Because mitochondrial dysfunc-\ntion is common in the brain of AD patients alongside increased Ab\nand reduced p3-Alcb37 levels, the administration of p3-Alcb9-19\nmay be a promising treatment for restoring, protecting, and pro-\nmoting brain functions in patients with AD.\nKeywords AD therapy; alcadein; Alzheimer\u2019s disease (AD); mitochondria; PET\nimaging\nSubject Category Neuroscience\nDOI 10.15252/emmm.202217052 | Received 16 October 2022 | Revised 14"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1289
encoding: FLOAT32
metadata:
{"title": "Brain p3-Alcb peptide restores neuronal viability impaired by Alzheimer\u2019s amyloid b-peptide", "chroma:document": "March 2023 | Accepted 14 March 2023 | Published online 30 March 2023\nEMBO Mol Med (2023) 15: e17052\nIntroduction\nAlzheimer\u2019s disease (AD) is an incurable neurodegenerative disor-\nder that causes progressive dementia in aged subjects. More than 50\nmillion people live with dementia worldwide and AD accounts for\n60\u201380% of these cases (World Alzheimer\u2019s Report, 2018). The gen-\neration and accumulation of neurotoxic amyloid b (Ab) protein, a\npathogenic hallmark in the AD brain, are believed to be the primary\ncause of neurodegeneration, resulting in cognitive deficits and mem-\nory loss (McLean et al, 1999; Hardy & Selkoe, 2002). In neurons, Ab\nis generated from Ab-protein precursor (APP), a single membrane-\nspanning protein, via intramembrane proteolysis of c-secretase after\nthe\nshedding\nof\nthe\nAPP\nextracellular/luminal\nregion\nby\nb-\nsecretase/BACE1 (De Strooper et al, 1998; Vassar et al, 1999; Thina-\nkaran & Koo, 2008).\nAlcadeins (Alcs)/calsyntenins (Clstns) are a family of type I trans-\nmembrane proteins expressed in neurons. This family includes alca-\ndein a (Alca/Clstn1), b (Alcb/Clstn3), and c (Alcc/Clstn2), which\nare\nencoded\nby\nseparate\ngenes\n(Hintsch\net\nal,\n2002;\nAraki\net al, 2003). Alca/Clstn1 is a cargo receptor of kinesin-1 (Konecna\n1\nLaboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan\n2\nBiomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan\n3\nAdvanced Prevention and Research Laboratory for Dementia, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan\n4\nCentral Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Japan\n5\nMolecular Genetics, Niigata University Brain Research Institute, Nigata, Japan\n6\nCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan\n7\nPeptide Institute, Inc., Ibaraki, Japan\n8"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1290
encoding: FLOAT32
metadata:
{"title": "Brain p3-Alcb peptide restores neuronal viability impaired by Alzheimer\u2019s amyloid b-peptide", "chroma:document": "8\nLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science Institute, Wako, Japan\n9\nDepartment of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan\n10\nDepartment of Molecular Neurobiology, Factory of Medicine, Kagawa University, Takamatsu, Japan\n11\nMolecular Neuroscience Research Center, Shiga University of Medical Science, Shiga, Japan\n12\nDepartment of Biofunctional Imaging, Preeminent Medical Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan\n*Corresponding author. Tel: +81 53 435 2466; E-mail: ouchi@hama-med.ac.jp\n**Corresponding author. Tel: +81 11 706 3250; E-mail: tsuzuki@pharm.hokudai.ac.jp\n\u2020These authors contributed equally to this work\n\u0001 2023 The Authors. Published under the terms of the CC BY 4.0 license.\nEMBO Molecular Medicine\n15: e17052 | 2023\n1 of 15"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1291
encoding: FLOAT32
metadata:
{"title": "Effect of a False Inertial Cue in the Velocity-Storage Circuit on Head Posture and Inertia Perception", "chroma:document": "Systems/Circuits\nEffect of a False Inertial Cue in the Velocity-Storage Circuit\non Head Posture and Inertia Perception\nJeong-Yoon Choi,1,2 Yu Jin Koo,1 Jung-Mi Song,1 Hyo-Jung Kim,3 and Ji-Soo Kim1,2\n1Dizziness Center, Clinical Neuroscience Center, and Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi\n13620 South Korea, 2Department of Neurology, Seoul National University College of Medicine, Seoul 03080, South Korea, and 3Research\nAdministration Team, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620 South Korea\nThe velocity-storage circuit participates in the vestibulopostural reflex, but its role in the postural reflex requires further elu-\ncidation. The velocity-storage circuit differentiates gravitoinertial information into gravitational and inertial cues using rota-\ntional cues. This implies that a false rotational cue can cause an erroneous estimation of gravity and inertial cues. We\nhypothesized the velocity-storage circuit is a common gateway for all vestibular reflex pathways and tested that hypothesis by\nmeasuring the postural and perceptual responses from a false inertial cue estimated in the velocity-storage circuit. Twenty\nhealthy human participants (40.5 6 8.2 years old, 6 men) underwent two different sessions of earth-vertical axis rotations at\n120\u00b0/s for 60 s. During each session, the participants were rotated clockwise and then counterclockwise with two different\nstarting head positions (head-down and head-up). During the first (control) session, the participants kept a steady head posi-\ntion at the end of rotation. During the second (test) session, the participants changed their head position at the end of rota-\ntion, from head-down to head-up or vice versa. The head position and inertial motion perception at the end of rotation were\naligned with the inertia direction anticipated by the velocity-storage model. The participants showed a significant correlation"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1292
encoding: FLOAT32
metadata:
{"title": "Effect of a False Inertial Cue in the Velocity-Storage Circuit on Head Posture and Inertia Perception", "chroma:document": "between postural and perceptual responses. The velocity-storage circuit appears to be a shared neural integrator for the vesti-\nbulopostural reflex and vestibular perception. Because the postural responses depended on the inertial direction, the postural\ninstability in vestibular disorders may be the consequence of the vestibulopostural reflex responding to centrally estimated\nfalse vestibular cues.\nKey words: perception; posture; velocity-storage; vestibular system\nSignificance Statement\nThe velocity-storage circuit appears to participate in the vestibulopostural reflex, which stabilizes the head and body position\nin space. However, it is still unclear whether the velocity-storage circuit for the postural reflex is in common with that\ninvolved in eye movement and perception. We evaluated the postural and perceptual responses to a false inertial cue esti-\nmated by the velocity-storage circuit. The postural and perceptual responses were consistent with the inertia direction pre-\ndicted in the velocity-storage model and were correlated closely with each other. These results show that the velocity-storage\ncircuit is a shared neural integrator for vestibular-driven responses and suggest that the vestibulopostural response to a false\nvestibular cue is the pathomechanism of postural instability clinically observed in vestibular disorders.\nIntroduction\nTo maintain head and body stability, humans must update and\nadjust their head and body positions in a given reference frame,\nsuch as head and body positions in space or the position of the\nhead on the body (Suzuki and Cohen, 1964; Goldberg and Cullen,\n2011). Although multisensorial inputs, such as vestibular, visual,\nproprioceptive, and efference copy cues, are involved in this func-\ntion, vestibular cues play a primary role in stabilizing head and\nbody positions in space through the vestibulocollic reflex (VCR)\nand vestibulospinal reflex (VSR; Angelaki and Cullen, 2008; Cullen,\n2011). This function also operates while standing upright through"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1293
encoding: FLOAT32
metadata:
{"title": "Effect of a False Inertial Cue in the Velocity-Storage Circuit on Head Posture and Inertia Perception", "chroma:document": "the righting reflex, a kind of VCR and VSR, which activates the\nneck and spine extensors to counteract the gravity force (Molina-\nNegro et al., 1980; Dichgans and Diener, 1989).\nDespite the common vestibular inputs, the vestibulopostural\nreflex shows a response distinct from that resulting from the\nReceived June 10, 2022; revised Dec. 16, 2022; accepted Jan. 8, 2023.\nAuthor contributions: J.-Y.C. and J.-M.S. designed research; Y.-J.K., J.-M.S., and H.-J.K. performed research;\nJ-Y.C., Y.-J.K., J.-M.S., and H.-J.K. contributed unpublished reagents/analytic tools; J.-Y.C., Y.-J.K., H.-J.K., and\nJ.-S.K. analyzed data; and J.-Y.C. and J.-S.K. wrote the paper.\nThis study was supported by the Basic Science Research Program through the National Research\nFoundation of Korea (NRF) funded by the Ministry of Science and ICT (2020R1A2C4002281).\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Jeong-Yoon Choi at saideiju@gmail.com.\nhttps://doi.org/10.1523/JNEUROSCI.1148-22.2023\nCopyright \u00a9 2023 the authors\n1530 \u2022 The Journal of Neuroscience, March 1, 2023 \u2022 43(9):1530\u20131539"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1294
encoding: FLOAT32
metadata:
{"title": "Nutrient-Sensitive Reinforcement Learning in Monkeys", "chroma:document": "Behavioral/Cognitive\nNutrient-Sensitive Reinforcement Learning in Monkeys\nFei-Yang Huang (\u9ec3\u98db\u63da)1,2 and\nFabian Grabenhorst1,2\n1Department of Experimental Psychology, University of Oxford, Oxford OX1 3TA, United Kingdom and 2Department of Physiology, Development\nand Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom\nIn reinforcement learning (RL), animals choose by assigning values to options and learn by updating these values from\nreward outcomes. This framework has been instrumental in identifying fundamental learning variables and their neuronal\nimplementations. However, canonical RL models do not explain how reward values are constructed from biologically critical\nintrinsic reward components, such as nutrients. From an ecological perspective, animals should adapt their foraging choices\nin dynamic environments to acquire nutrients that are essential for survival. Here, to advance the biological and ecological\nvalidity of RL models, we investigated how (male) monkeys adapt their choices to obtain preferred nutrient rewards under\nvarying reward probabilities. We found that the nutrient composition of rewards strongly influenced learning and choices.\nPreferences of the animals for specific nutrients (sugar, fat) affected how they adapted to changing reward probabilities; the\nhistory of recent rewards influenced choices of the monkeys more strongly if these rewards contained the their preferred\nnutrients (nutrient-specific reward history). The monkeys also chose preferred nutrients even when they were associated with\nlower reward probability. A nutrient-sensitive RL model captured these processes; it updated the values of individual sugar\nand fat components of expected rewards based on experience and integrated them into subjective values that explained the\nchoices of the monkeys. Nutrient-specific reward prediction errors guided this value-updating process. Our results identify\nnutrients as important reward components that guide learning and choice by influencing the subjective value of choice"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1295
encoding: FLOAT32
metadata:
{"title": "Nutrient-Sensitive Reinforcement Learning in Monkeys", "chroma:document": "options. Extending RL models with nutrient-value functions may enhance their biological validity and uncover nutrient-spe-\ncific learning and decision variables.\nKey words: food; learning; nutrients; preference; reward; reward prediction error\nSignificance Statement\nRL is an influential framework that formalizes how animals learn from experienced rewards. Although reward is a founda-\ntional concept in RL theory, canonical RL models cannot explain how learning depends on specific reward properties, such as\nnutrients. Intuitively, learning should be sensitive to the nutrient components of the reward to benefit health and survival.\nHere, we show that the nutrient (fat, sugar) composition of rewards affects how the monkeys choose and learn in an RL paradigm\nand that key learning variables including reward history and reward prediction error should be modified with nutrient-specific\ncomponents to account for the choice behavior observed in the monkeys. By incorporating biologically critical nutrient rewards\ninto the RL framework, our findings help advance the ecological validity of RL models.\nIntroduction\nAccording to reinforcement learning (RL) theory, animals\nchoose by assigning values to options and learn by updating\nthese values from experienced rewards (Sutton and Barto, 1998).\nThis framework has been instrumental in identifying learning\nand decision variables that explain animal behavior, including\nobject values and action values, which guide choices, and reward\nprediction errors, which update values from experienced out-\ncomes. Physical implementations of these concepts have been\ndiscovered in neurons of the primate dopamine system, striatum,\namygdala, and frontal cortex (Schultz et al., 1997; Samejima et\nal., 2005; Lau and Glimcher, 2008; So and Stuphorn, 2010; Lee et\nal., 2012; Seo et al., 2012; Tsutsui et al., 2016; Costa et al., 2019;\nGrabenhorst et al., 2019a). One important factor that limits the\nbiological validity of canonical RL models is that they do not"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1296
encoding: FLOAT32
metadata:
{"title": "Nutrient-Sensitive Reinforcement Learning in Monkeys", "chroma:document": "explain how learning and choice depend on the composition of\nexperienced rewards. Nutrients, for example, are biologically\ncritical intrinsic components of food rewards that engage\ndedicated sensory and physiological mechanisms and are\nessential for survival (Carreiro et al., 2016; Rolls, 2020;\nSimpson and Raubenheimer, 2020). Thus, investigating how\nReceived Apr. 16, 2022; revised Nov. 27, 2022; accepted Dec. 19, 2022.\nAuthor contributions: F.-Y.H. and F.G. designed research; F.-Y.H. and F.G. performed research; F.-Y.H. and\nF.G. analyzed data; F.-Y.H. and F.G. wrote the paper.\nThis work was supported by Wellcome Trust Grants 206207/Z/17/Z and 206207/Z/17/A to F.G. F.-Y.H. was\nsupported by a fellowship from the Taiwan Ministry of Education. We thank Wolfram Schultz and group for\nsupport and discussions, Putu Khorisantono for discussions, Christina Thompson and Aled David for animal\ncare, Polly Taylor for anesthesia, and Henri Bertrand for veterinary care.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Fabian Grabenhorst at fabian.grabenhorst@psy.ox.ac.uk.\nhttps://doi.org/10.1523/JNEUROSCI.0752-22.2022\nCopyright \u00a9 2023 the authors\n1714 \u2022 The Journal of Neuroscience, March 8, 2023 \u2022 43(10):1714\u20131730"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1297
encoding: FLOAT32
metadata:
{"title": "Neurons in Primate Area MSTd Signal Eye Movement Direction Inferred from Dynamic Perspective Cues in Optic Flow", "chroma:document": "Systems/Circuits\nNeurons in Primate Area MSTd Signal Eye Movement\nDirection Inferred from Dynamic Perspective Cues in Optic\nFlow\nGrace F. DiRisio,1,4\nYongsoo Ra,1,2 Yinghui Qiu,1,3 Akiyuki Anzai,1 and\nGregory C. DeAngelis1\n1Department of Brain and Cognitive Sciences, Center for Visual Science, University of Rochester, Rochester, New York 14627, 2Department of\nNeurobiology, Harvard Medical School, Boston, Massachusetts 02115, 3College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-\n6401, and 4Department of Neurobiology, University of Chicago, Chicago, Illinois 60637\nSmooth eye movements are common during natural viewing; we frequently rotate our eyes to track moving objects or to\nmaintain fixation on an object during self-movement. Reliable information about smooth eye movements is crucial to various\nneural computations, such as estimating heading from optic flow or judging depth from motion parallax. While it is well\nestablished that extraretinal signals (e.g., efference copies of motor commands) carry critical information about eye velocity,\nthe rotational optic flow field produced by eye rotations also carries valuable information. Although previous work has shown\nthat dynamic perspective cues in optic flow can be used in computations that require estimates of eye velocity, it has\nremained unclear where and how the brain processes these visual cues and how they are integrated with extraretinal signals\nregarding eye rotation. We examined how neurons in the dorsal region of the medial superior temporal area (MSTd) of two\nmale rhesus monkeys represent the direction of smooth pursuit eye movements based on both visual cues (dynamic perspec-\ntive) and extraretinal signals. We find that most MSTd neurons have matched preferences for the direction of eye rotation\nbased on visual and extraretinal signals. Moreover, neural responses to combinations of these signals are well predicted by a"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1298
encoding: FLOAT32
metadata:
{"title": "Neurons in Primate Area MSTd Signal Eye Movement Direction Inferred from Dynamic Perspective Cues in Optic Flow", "chroma:document": "weighted linear summation model. These findings demonstrate a neural substrate for representing the velocity of smooth eye\nmovements based on rotational optic flow and establish area MSTd as a key node for integrating visual and extraretinal sig-\nnals into a more generalized representation of smooth eye movements.\nKey words: eye movements; motion processing; optic flow; smooth pursuit; visual cortex\nSignificance Statement\nWe frequently rotate our eyes to smoothly track objects of interest during self-motion. Information about eye velocity is cru-\ncial for a variety of computations performed by the brain, including depth perception and heading perception. Traditionally,\ninformation about eye rotation has been thought to arise mainly from extraretinal signals, such as efference copies of motor\ncommands. Previous work shows that eye velocity can also be inferred from rotational optic flow that accompanies smooth\neye movements, but the neural origins of these visual signals about eye rotation have remained unknown. We demonstrate\nthat macaque neurons signal the direction of smooth eye rotation based on visual signals, and that they integrate both visual\nand extraretinal signals regarding eye rotation in a congruent fashion.\nIntroduction\nDuring natural viewing, we rotate and reorient our body, head,\nand eyes to focus on relevant objects and collect information\nabout the visual scene. When the eyes rotate smoothly to track a\ntarget of interest, there are associated motor signals (i.e., effer-\nence copies of motor commands), and there are also visual con-\nsequences in the form of global optic flow. Traditionally, these\nvisual consequences have been considered undesirable, thus\nrequiring compensation by extraretinal signals such as efference\ncopies of motor commands (von Holst and Mittelstaedt, 1950;\nWallach, 1987; Royden et al., 1992; Bradley et al., 1996; Ben\nHamed et al., 2003). However, theoretical work has emphasized\nReceived Oct. 5, 2022; revised Jan. 18, 2023; accepted Jan. 24, 2023."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1299
encoding: FLOAT32
metadata:
{"title": "Neurons in Primate Area MSTd Signal Eye Movement Direction Inferred from Dynamic Perspective Cues in Optic Flow", "chroma:document": "Author contributions: A.A. and G.C.D. designed research; G.F.D., Y.R., and Y.Q. performed research; A.A.\ncontributed unpublished reagents/analytic tools; G.F.D., Y.R., Y.Q., and G.C.D. analyzed data; G.F.D. and G.C.D.\nwrote the paper.\nThis work was supported by National Eye Institute (NEI) Grant R01-EY-013644 and by Core Grant EY-\n001319 from the NEI. We thank Johnny Wen and Amanda Yung for assistance with the programming of\nvisual stimuli. We also thank Dina Graf and Emily Murphy for assistance with animal training and care. In\naddition, we thank Marjena Popovic for assistance with data collection for one animal.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Gregory C. DeAngelis at gdeangelis@ur.rochester.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1885-22.2023\nCopyright \u00a9 2023 the authors\n1888 \u2022 The Journal of Neuroscience, March 15, 2023 \u2022 43(11):1888\u20131904"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1300
encoding: FLOAT32
metadata:
{"title": "Vestibular Contributions to Primate Neck Postural Muscle Activity during Natural Motion", "chroma:document": "Systems/Circuits\nVestibular Contributions to Primate Neck Postural Muscle\nActivity during Natural Motion\nRobyn L. Mildren and\nKathleen E. Cullen\nDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205\nTo maintain stable posture of the head and body during our everyday activities, the brain integrates information across mul-\ntiple sensory systems. Here, we examined how the primate vestibular system, independently and in combination with visual\nsensory input, contributes to the sensorimotor control of head posture across the range of dynamic motion experienced dur-\ning daily life. We recorded activity of single motor units in the splenius capitis and sternocleidomastoid muscles in rhesus\nmonkeys during yaw rotations spanning the physiological range of self-motion (up to 20Hz) in darkness. Splenius capitis motor\nunit responses continued to increase with frequency up to 16Hz in normal animals, and were strikingly absent following bilateral\nperipheral vestibular loss. To determine whether visual information modulated these vestibular-driven neck muscle responses, we\nexperimentally controlled the correspondence between visual and vestibular cues of self-motion. Surprisingly, visual information\ndid not influence motor unit responses in normal animals, nor did it substitute for absent vestibular feedback following bilateral\nperipheral vestibular loss. A comparison of muscle activity evoked by broadband versus sinusoidal head motion further revealed\nthat low-frequency responses were attenuated when low- and high-frequency self-motion were experienced concurrently. Finally,\nwe found that vestibular-evoked responses were enhanced by increased autonomic arousal, quantified via pupil size. Together, our\nfindings directly establish the vestibular system\u2019s contribution to the sensorimotor control of head posture across the dynamic\nmotion range experienced during everyday activities, as well as how vestibular, visual, and autonomic inputs are integrated for pos-\ntural control."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1301
encoding: FLOAT32
metadata:
{"title": "Vestibular Contributions to Primate Neck Postural Muscle Activity during Natural Motion", "chroma:document": "Key words: motor unit; natural motion; neck muscle; postural control; vestibular; vestibulocollic\nSignificance Statement\nOur sensory systems enable us to maintain control of our posture and balance as we move through the world. Notably, the\nvestibular system senses motion of the head and sends motor commands, via vestibulospinal pathways, to axial and limb\nmuscles to stabilize posture. By recording the activity of single motor units, here we show, for the first time, that the vestibu-\nlar system contributes to the sensorimotor control of head posture across the dynamic motion range experienced during\neveryday activities. Our results further establish how vestibular, autonomic, and visual inputs are integrated for postural con-\ntrol. This information is essential for understanding both the mechanisms underlying the control of posture and balance, and\nthe impact of the loss of sensory function.\nIntroduction\nThe ability to maintain posture and balance during our everyday\nactivities requires the integration of multiple sensory and motor\nsignals. In this context, the vestibular organs provide essential in-\nformation about motion of the head in space, which is rapidly\ntransmitted via central vestibular pathways to drive compensatory\nvestibulospinal reflexes that help stabilize head and body posture\n(Roy and Cullen, 2001; Cullen and Roy, 2004; Brooks and Cullen,\n2013). To date, however, the vestibular system\u2019s contributions to\nthe control of posture during natural motion experienced in daily\nlife, both independently and in combination with other sensory\ncues, are not well understood.\nIn this context, the pathways responsible for stabilizing the\nhead relative to space constitute an excellent model to under-\nstand the vestibular system\u2019s contribution to postural control.\nFirst, the central brainstem and cerebellar vestibular circuits that\nmediate compensatory neck muscle responses have been well\ncharacterized in primates (Roy and Cullen, 2001; Cullen and\nRoy, 2004; Brooks and Cullen, 2013; Zobeiri and Cullen, 2022)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1302
encoding: FLOAT32
metadata:
{"title": "Vestibular Contributions to Primate Neck Postural Muscle Activity during Natural Motion", "chroma:document": "Second, relative to the complex biomechanics of the appendicu-\nlar system, the biomechanics of head-on-body motion in the yaw\nplane are relatively simple because the majority of movement\nReceived Sep. 26, 2022; revised Jan. 10, 2023; accepted Feb. 13, 2023.\nAuthor contributions: R.L.M. and K.E.C. designed research; R.L.M. performed research; R.L.M. analyzed\ndata; R.L.M. wrote the first draft of the paper; R.L.M. and K.E.C. edited the paper; R.L.M. and K.E.C. wrote the\npaper.\nWe thank Olivia Leavitt for assistance with the modeling; oMid Zobeiri and Dale Roberts for technical\nassistance; and Oliver Stanley, Dr. Patrick Forbes, and Dr. Silvia Muceli for critical feedback on the manuscript.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Kathleen E. Cullen at kathleen.cullen@jhu.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1831-22.2023\nCopyright \u00a9 2023 the authors\n2326 \u2022 The Journal of Neuroscience, March 29, 2023 \u2022 43(13):2326\u20132337"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1303
encoding: FLOAT32
metadata:
{"title": "Shared Neural Activity But Distinct Neural Dynamics for Cognitive Control in Monkey Prefrontal and Parietal Cortex", "chroma:document": "Behavioral/Cognitive\nShared Neural Activity But Distinct Neural Dynamics for\nCognitive Control in Monkey Prefrontal and Parietal Cortex\nRachael K. Blackman,1,2,3 David A. Crowe,2,4 Adele L. DeNicola,1,2 Sofia Sakellaridi,1,2\nJacob A. Westerberg,5\nAnh M. Huynh,4 Angus W. MacDonald,6 Scott R. Sponheim,7,8 and Matthew V. Chafee1,2\n1Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, 2Brain Sciences Center, VA Medical Center, Minneapolis,\nMinnesota 55417, 3Medical Scientist Training Program (MD/PhD), University of Minnesota, Minneapolis, Minnesota 55455, 4Department of\nBiology, Augsburg University, Minneapolis, Minnesota 55454, 5Neuroscience Program, St. Olaf College, Northfield, Minnesota 55057, 6Department\nof Psychology, University of Minnesota, Minneapolis, Minnesota 55455, 7Minneapolis VA Health Care System, Minneapolis, Minnesota 55417, and\n8Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota 55454\nTo better understand how prefrontal networks mediate forms of cognitive control disrupted in schizophrenia, we translated a vari-\nant of the AX continuous performance task that measures specific deficits in the human disease to 2 male monkeys and recorded\nneurons in PFC and parietal cortex during task performance. In the task, contextual information instructed by cue stimuli deter-\nmines the response required to a subsequent probe stimulus. We found parietal neurons encoding the behavioral context instructed\nby cues that exhibited nearly identical activity to their prefrontal counterparts (Blackman et al., 2016). This neural population\nswitched their preference for stimuli over the course of the trial depending on whether the stimuli signaled the need to engage cog-\nnitive control to override a prepotent response. Cues evoked visual responses that appeared in parietal neurons first, whereas popu-\nlation activity encoding contextual information instructed by cues was stronger and more persistent in PFC. Increasing cognitive"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1304
encoding: FLOAT32
metadata:
{"title": "Shared Neural Activity But Distinct Neural Dynamics for Cognitive Control in Monkey Prefrontal and Parietal Cortex", "chroma:document": "control demand biased the representation of contextual information toward the PFC and augmented the temporal correlation of\ntask-defined information encoded by neurons in the two areas. Oscillatory dynamics in local field potentials differed between corti-\ncal areas and carried as much information about task conditions as spike rates. We found that, at the single-neuron level, patterns\nof activity evoked by the task were nearly identical between the two cortical areas. Nonetheless, distinct population dynamics in\nPFC and parietal cortex were evident. suggesting differential contributions to cognitive control.\nKey words: AX-CPT; cognitive control; monkey; parietal; prefrontal; schizophrenia\nSignificance Statement\nWe recorded neural activity in PFC and parietal cortex of monkeys performing a task that measures cognitive control deficits\nin schizophrenia. This allowed us to characterize computations performed by neurons in the two areas to support forms of\ncognitive control disrupted in the disease. Subpopulations of neurons in the two areas exhibited parallel modulations in firing\nrate; and as a result, all patterns of task-evoked activity were distributed between PFC and parietal cortex. This included the\npresence in both cortical areas of neurons reflecting proactive and reactive cognitive control dissociated from stimuli or\nresponses in the task. However, differences in the timing, strength, synchrony, and correlation of information encoded by\nneural activity were evident, indicating differential contributions to cognitive control.\nReceived Aug. 28, 2022; revised Jan. 15, 2023; accepted Feb. 15, 2023.\nAuthor contributions: R.K.B., D.A.C., A.L.D., S.S., A.W.M., S.R.S., and M.V.C. designed research;\nR.K.B., D.A.C., A.L.D., S.S., and M.V.C. performed research; R.K.B., D.A.C., A.L.D., J.A.W., A.M.H., and M.V.C.\nanalyzed data; R.K.B., D.A.C., A.L.D., S.S., J.A.W., A.M.H., A.W.M., S.R.S., and M.V.C. edited the paper;\nR.K.B., D.A.C., and M.V.C. wrote the paper."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1305
encoding: FLOAT32
metadata:
{"title": "Shared Neural Activity But Distinct Neural Dynamics for Cognitive Control in Monkey Prefrontal and Parietal Cortex", "chroma:document": "This work was supported by National Institutes of Health R01MH077779, R01MH107491, and\nP50MH119569; the Department of Veterans Affairs; the American Brain Sciences Chair; the Wilfred Wetzel\nGraduate Fellowship; and National Institute of General Medical Sciences T32 GM008244 and T32 HD007151.\nThis work was performed while R.K.B. was employed at the University of Minnesota. The opinions expressed\nin this article are the author\u2019s own and do not reflect the views of the National Institutes of Health, the\nDepartment of Health and Human Services, or the U.S. Government. This material is the result of work\nsupported with resources and the use of facilities at the Minneapolis VA Health Care System. The contents do\nnot represent the views of the U.S. Department of Veterans Affairs, the National Institutes of Health, the\nDepartment of Health and Human Services, or the U.S. Government. We thank C. Dean Evans for technical\nassistance during surgeries and neural recordings as well as exemplary animal care; Dale Boeff for assistance\nwith computer programming as well as design and construction of neurophysiological recording equipment;\nand A.D. Reddish for insightful suggestions regarding the decoding analyses.\nR. K. Blackman\u2019s present address: National Institute of Mental Health, National Institutes of Health,\nBethesda, MD 20892.\nA. L. DeNicola\u2019s present address: Department of Neurology, University of Minnesota, Minneapolis, MN 55455.\nS. Sakellaridi\u2019s present address: Bioengineering Department, University of California Riverside, Riverside, CA 92521.\nJ. A. Westerberg\u2019s present address: Department of Vision and Cognition, Netherlands Institute for\nNeuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Matthew V. Chafee at chafe001@umn.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1641-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, April 12, 2023 \u2022 43(15):2767\u20132781 \u2022 2767"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1306
encoding: FLOAT32
metadata:
{"title": "Monkey Dorsolateral Prefrontal Cortex Represents Abstract Visual Sequences during a No-Report Task", "chroma:document": "Behavioral/Cognitive\nMonkey Dorsolateral Prefrontal Cortex Represents Abstract\nVisual Sequences during a No-Report Task\nNadira Yusif Rodriguez,1,2 Theresa H. McKim,1 Debaleena Basu,1 Aarit Ahuja,1,2 and\nTheresa M. Desrochers1,2,3\n1Department of Neuroscience, Brown University, Providence, RI 02912, 2Robert J. and Nancy D. Carney Institute for Brain Science, Brown\nUniversity, Providence, RI 02912, and 3Department of Psychiatry and Human Behavior, Brown University, Providence, RI 02912\nMonitoring sequential information is an essential component of our daily lives. Many of these sequences are\nabstract, in that they do not depend on the individual stimuli, but do depend on an ordered set of rules (e.g., chop\nthen stir when cooking). Despite the ubiquity and utility of abstract sequential monitoring, little is known about its\nneural mechanisms. Human rostrolateral prefrontal cortex (RLPFC) exhibits specific increases in neural activity (i.e.,\n\u201cramping\u201d) during abstract sequences. Monkey dorsolateral prefrontal cortex (DLPFC) has been shown to represent\nsequential information in motor (not abstract) sequence tasks, and contains a subregion, area 46, with homologous\nfunctional connectivity to human RLPFC. To test the prediction that area 46 may represent abstract sequence infor-\nmation, and do so with parallel dynamics to those found in humans, we conducted functional magnetic resonance\nimaging (fMRI) in three male monkeys. When monkeys performed no-report abstract sequence viewing, we found\nthat left and right area 46 responded to abstract sequential changes. Interestingly, responses to rule and number\nchanges overlapped in right area 46 and left area 46 exhibited responses to abstract sequence rules with changes in\nramping activation, similar to that observed in humans. Together, these results indicate that monkey DLPFC moni-\ntors abstract visual sequential information, potentially with a preference for different dynamics in the two hemi-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1307
encoding: FLOAT32
metadata:
{"title": "Monkey Dorsolateral Prefrontal Cortex Represents Abstract Visual Sequences during a No-Report Task", "chroma:document": "spheres. More generally, these results show that abstract sequences are represented in functionally homologous\nregions across monkeys and humans.\nKey words: abstract sequence; fMRI; nonhuman primate; prefrontal cortex; ramping activation\nSignificance Statement\nDaily, we complete sequences that are \u201cabstract\u201d because they depend on an ordered set of rules (e.g., chop then stir when\ncooking) rather than the identity of individual items. Little is known about how the brain tracks, or monitors, this abstract se-\nquential information. Based on previous human work showing abstract sequence related dynamics in an analogous area, we\ntested whether monkey dorsolateral prefrontal cortex (DLPFC), specifically area 46, represents abstract sequential informa-\ntion using awake monkey functional magnetic resonance imaging (fMRI). We found that area 46 responded to abstract\nsequence changes, with a preference for more general responses on the right and dynamics similar to humans on the left.\nThese results suggest that abstract sequences are represented in functionally homologous regions across monkeys and\nhumans.\nReceived Nov. 1, 2022; revised Feb. 22, 2023; accepted Feb. 24, 2023.\nAuthor contributions: N.Y.R. and T.M.D. designed research; N.Y.R., T.H.M., D.B., A.A., and T.M.D. performed\nresearch; N.Y.R., T.H.M., D.B., A.A., and T.M.D. contributed unpublished reagents/analytic tools; N.Y.R. and\nT.M.D. analyzed data; N.Y.R. and T.M.D. wrote the first draft of the paper; N.Y.R., T.H.M., D.B., A.A., and\nT.M.D. edited the paper; N.Y.R. and T.M.D. wrote the paper.\nThis study was supported by the National Science Foundation (NSF) Established Program to Stimulate Competitive\nResearch (EPSCoR) Neural Basis of Attention Grant 1632738 (N.Y.R. and T.M.D.), the National Institute of General\nMedical Sciences (NIGMS)-National Institutes of Health (NIH) Initiative to Maximize Student Development Grant IMSD\nR25GM083270 (N.Y.R.), the NIH-NIGMS Grant COBRE P20GM103645 (T.M.D), NIH National Institutes of Mental Health"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1308
encoding: FLOAT32
metadata:
{"title": "Monkey Dorsolateral Prefrontal Cortex Represents Abstract Visual Sequences during a No-Report Task", "chroma:document": "(NIMH) R21MH125010 (T.M.D.), NSF Faculty Early Career Development (CAREER) Program Award 2143656 (T.M.D.), and\nthe Carney Institute for Brain Science Innovation Award (T.M.D.). Part of this research was conducted using\ncomputational resources and services at the Center for Computation and Visualization, Brown University (NIH Grant\nS10OD025181). We thank Matthew Maestri for his assistance with animal training and data collection. We thank Dr.\nMichael Worden, Lynn Fanella, Fabienne McEleney, and Brown University\u2019s MRI Facilities staff for their support and\nguidance throughout this project. We also thank Dr. David Sheinberg, Dr. David Badre, Dr. Amitai Shenhav, Dr. Katherine\nConen, and Dr. Diana Burk for their continued support throughout this project and preparation of this publication as well\nas members of both the Sheinberg and the Desrochers Labs for many helpful discussions and contributions.\nT. H. McKim\u2019s present address: Department of Child and Adolescent Psychiatry, Psychosomatics and\nPsychotherapy, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany, 97080.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Theresa M. Desrochers at theresa_desrochers@brown.edu.\nhttps://doi.org/10.1523/JNEUROSCI.2058-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, April 12, 2023 \u2022 43(15):2741\u20132755 \u2022 2741"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1309
encoding: FLOAT32
metadata:
{"title": "Spatiotemporal Live-Cell Analysis of Photoreceptor Outer Segment Membrane Ingestion by the Retinal Pigment Epithelium Reveals Actin-Regulated Scission", "chroma:document": "Cellular/Molecular\nSpatiotemporal Live-Cell Analysis of Photoreceptor Outer\nSegment Membrane Ingestion by the Retinal Pigment\nEpithelium Reveals Actin-Regulated Scission\nAnkita Umapathy, Gil Torten, Antonio E. Paniagua, Julie Chung, Madeline Tomlinson, Caleb Lim, and\nDavid S. Williams\nDepartment of Ophthalmology and Stein Eye Institute, and Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles,\nCalifornia 90095\nThe photoreceptor outer segment (OS) is the phototransductive organelle in the vertebrate retina. OS tips are regularly\ningested and degraded by the adjacent retinal pigment epithelium (RPE), offsetting the addition of new disk membrane at\nthe base of the OS. This catabolic role of the RPE is essential for photoreceptor health, with defects in ingestion or degrada-\ntion underlying different forms of retinal degeneration and blindness. Although proteins required for OS tip ingestion have\nbeen identified, spatiotemporal analysis of the ingestion process in live RPE cells is lacking; hence, the literature reflects no\ncommon understanding of the cellular mechanisms that affect ingestion. We imaged live RPE cells from mice (both sexes) to\nelucidate the ingestion events in real time. Our imaging revealed roles for f-actin dynamics and specific dynamic localizations\nof two BAR (Bin-Amphiphysin-Rvs) proteins, FBP17 and AMPH1-BAR, in shaping the RPE apical membrane as it surrounds\nthe OS tip. Completion of ingestion was observed to occur by scission of the OS tip from the remainder of the OS, with a\ntransient concentration of f-actin forming around the site of imminent scission. Actin dynamics were also required for regu-\nlating the size of the ingested OS tip, and the time course of the overall ingestion process. The size of the ingested tip is con-\nsistent with the term \u201cphagocytosis.\u201d However, phagocytosis usually refers to engulfment of an entire particle or cell, whereas"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1310
encoding: FLOAT32
metadata:
{"title": "Spatiotemporal Live-Cell Analysis of Photoreceptor Outer Segment Membrane Ingestion by the Retinal Pigment Epithelium Reveals Actin-Regulated Scission", "chroma:document": "our observations of OS tip scission indicate a process that is more specifically described as \u201ctrogocytosis,\u201d in which one cell\n\u201cnibbles\u201d another cell.\nKey words: actin dynamics; BAR proteins; live-cell imaging; phagocytosis; RPE; trogocytosis\nSignificance Statement\nThe ingestion of the photoreceptor outer segment (OS) tips by the retinal pigment epithelium (RPE) is a dynamic cellular pro-\ncess that has fascinated scientists for 60years. Yet its molecular mechanisms had not been addressed in living cells. We devel-\noped a live-cell imaging approach to investigate OS tip ingestion, and focused on the dynamic participation of actin filaments\nand membrane-shaping BAR proteins. We observed scission of OS tips for the first time, and were able to monitor local\nchanges in protein concentration preceding, during, and following scission. Our approach revealed that actin filaments were\nconcentrated at the site of OS scission and were required for regulating the size of the ingested OS tip and the time course of\nthe ingestion process.\nIntroduction\nThe retinal pigment epithelium (RPE) is an extraordinary epithe-\nlium. It performs several specialized functions that are crucial to\nthe maintenance of vision (Strauss, 2005; Lakkaraju et al., 2020).\nIn one such function, it takes care of the catabolic phase of pho-\ntoreceptor outer segment (OS) renewal. OSs are composed of\ntightly packed membranous disks, which contain the phototrans-\nductive proteins. The distal tip, amounting to ;10% of each OS\nin mammals, is phagocytosed by the RPE each day (Young, 1967;\nYoung and Bok, 1969). Given that each RPE cell interfaces with\nnumerous photoreceptors, .200 in the central mouse retina\n(Volland et al., 2015), it must ingest and degrade large amounts\nReceived Sep. 9, 2022; revised Jan. 16, 2023; accepted Jan. 18, 2023.\nAuthor contributions: A.U., G.T., and D.S.W. designed research; A.U., G.T., A.E.P., J.C., M.T., and C.L.\nperformed research; A.U., G.T., J.C., M.T., C.L., D.S.W., and A.P. analyzed data; A.U. and D.S.W. wrote the\npaper."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1311
encoding: FLOAT32
metadata:
{"title": "Spatiotemporal Live-Cell Analysis of Photoreceptor Outer Segment Membrane Ingestion by the Retinal Pigment Epithelium Reveals Actin-Regulated Scission", "chroma:document": "paper.\nThe study was supported by NIH NEI grants R01EY027442, R01EY033035, R21EY031109, T32EY007026, and\nP30EY00333, and a program project grant from the Foundation Fighting Blindness. We thank Barry Burgess\nfor technical support, Fei Yu for assistance with statistical analysis, and Michael Schell for generously\nproviding the F-Tractin constructs.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to David S. Williams at dswilliams@ucla.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1726-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, April 12, 2023 \u2022 43(15):2653\u20132664 \u2022 2653"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1312
encoding: FLOAT32
metadata:
{"title": "Sound Improves Neuronal Encoding of Visual Stimuli in Mouse Primary Visual Cortex", "chroma:document": "Systems/Circuits\nSound Improves Neuronal Encoding of Visual Stimuli in\nMouse Primary Visual Cortex\nAaron M. Williams,1,2,3\nChristopher F. Angeloni,1,4 and\nMaria N. Geffen1,2,3\n1Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, 2Department of Neuroscience, University of\nPennsylvania, Philadelphia, Pennsylvania, 19104, 3Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, and\n4Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104\nIn everyday life, we integrate visual and auditory information in routine tasks such as navigation and communication.\nWhile concurrent sound can improve visual perception, the neuronal correlates of audiovisual integration are not\nfully understood. Specifically, it remains unclear whether neuronal firing patters in the primary visual cortex (V1) of\nawake animals demonstrate similar sound-induced improvement in visual discriminability. Furthermore, presentation\nof sound is associated with movement in the subjects, but little is understood about whether and how sound-associ-\nated movement affects audiovisual integration in V1. Here, we investigated how sound and movement interact to\nmodulate V1 visual responses in awake, head-fixed mice and whether this interaction improves neuronal encoding of\nthe visual stimulus. We presented visual drifting gratings with and without simultaneous auditory white noise to\nawake mice while recording mouse movement and V1 neuronal activity. Sound modulated activity of 80% of light-\nresponsive neurons, with 95% of neurons increasing activity when the auditory stimulus was present. A generalized\nlinear model (GLM) revealed that sound and movement had distinct and complementary effects of the neuronal visual\nresponses. Furthermore, decoding of the visual stimulus from the neuronal activity was improved with sound, an\neffect that persisted even when controlling for movement. These results demonstrate that sound and movement modu-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1313
encoding: FLOAT32
metadata:
{"title": "Sound Improves Neuronal Encoding of Visual Stimuli in Mouse Primary Visual Cortex", "chroma:document": "late visual responses in complementary ways, improving neuronal representation of the visual stimulus. This study\nclarifies the role of movement as a potential confound in neuronal audiovisual responses and expands our knowledge\nof how multimodal processing is mediated at a neuronal level in the awake brain.\nKey words: auditory cortex; electrophysiology; multimodal; visual cortex; visual processing\nSignificance Statement\nSound and movement are both known to modulate visual responses in the primary visual cortex; however, sound-\ninduced movement has largely remained unaccounted for as a potential confound in audiovisual studies in awake\nanimals. Here, authors found that sound and movement both modulate visual responses in an important visual\nbrain area, the primary visual cortex, in distinct, yet complementary ways. Furthermore, sound improved encoding\nof the visual stimulus even when accounting for movement. This study reconciles contrasting theories on the mech-\nanism underlying audiovisual integration and asserts the primary visual cortex as a key brain region participating\nin tripartite sensory interactions.\nIntroduction\nOur brains use incoming sensory information to generate a\ncontinuous perceptual experience across sensory modal-\nities. The neuronal systems underlying sensory perception\nof different modalities interact in a way that often improves\nperception of the complementary modality (Gingras et al.,\n2009; Gleiss and Kayser, 2012; Bigelow and Poremba, 2016;\nHammond-Kenny et al., 2017; Meijer et al., 2018; Stein et\nal., 2020). In the audiovisual realm, it is often easiest to\nunderstand what someone is saying in a crowded room by\nadditionally relying on visual cues such as lip movement\nand facial expression (Maddox et al., 2015; Tye-Murray et\nReceived Dec. 2, 2021; revised Feb. 14, 2023; accepted Feb. 23, 2023.\nAuthor contributions: A.M.W. and M.N.G. designed research; A.M.W., C.F.A., and M.N.G. performed"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1314
encoding: FLOAT32
metadata:
{"title": "Sound Improves Neuronal Encoding of Visual Stimuli in Mouse Primary Visual Cortex", "chroma:document": "research; A.M.W. and C.F.A. contributed unpublished reagents/analytic tools; A.M.W. and C.F.A. analyzed data;\nA.M.W. and M.N.G. wrote the first draft of the paper; A.M.W., C.F.A., and M.N.G. edited the paper; A.M.W.\nand M.N.G. wrote the paper.\nThis work was supported by National Institute of Health National Institute on Deafness and Other\nCommunication Disorders Grants 5T32DC016903 (to A.M.W. and C.F.A.), F31DC016524 (to C.F.A.), and\nR01DC015527, R01DC014479, and R01NS113241 (to M.N.G.). We thank Gabrielle Samulewicz for assistance\nwith experiments and members of the Geffen laboratory for helpful discussions, as well as Dr. Jay Gottfried\nand Dr. Yale Cohen at the University of Pennsylvania.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Maria N. Geffen at mgeffen@pennmedicine.upenn.edu.\nhttps://doi.org/10.1523/JNEUROSCI.2444-21.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, April 19, 2023 \u2022 43(16):2885\u20132906 \u2022 2885"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1315
encoding: FLOAT32
metadata:
{"title": "Face-Selective Patches in Marmosets Are Involved in Dynamic and Static Facial Expression Processing", "chroma:document": "Systems/Circuits\nFace-Selective Patches in Marmosets Are Involved in\nDynamic and Static Facial Expression Processing\nAudrey Dureux,1 Alessandro Zanini,1 and\nStefan Everling1,2\n1Centre for Functional and Metabolic Mapping, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, Canada and\n2Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5K8, Canada\nThe correct identification of facial expressions is critical for understanding the intention of others during social communica-\ntion in the daily life of all primates. Here we used ultra-high-field fMRI at 9.4 T to investigate the neural network activated\nby facial expressions in awake New World common marmosets from both male and female sex, and to determine the effect\nof facial motions on this network. We further explored how the face-patch network is involved in the processing of facial\nexpressions. Our results show that dynamic and static facial expressions activate face patches in temporal and frontal areas\n(O, PV, PD, MD, AD, and PL) as well as in the amygdala, with stronger responses for negative faces, also associated with an\nincrease of the respiration rates of the monkey. Processing of dynamic facial expressions involves an extended network\nrecruiting additional regions not known to be part of the face-processing network, suggesting that face motions may facilitate\nthe recognition of facial expressions. We report for the first time in New World marmosets that the perception and identifi-\ncation of changeable facial expressions, vital for social communication, recruit face-selective brain patches also involved in\nface detection processing and are associated with an increase of arousal.\nKey words: awake marmosets; faces; facial expressions; fMRI; respiration rate; social communication\nSignificance Statement\nRecent research in humans and nonhuman primates has highlighted the importance to correctly recognize and process facial"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1316
encoding: FLOAT32
metadata:
{"title": "Face-Selective Patches in Marmosets Are Involved in Dynamic and Static Facial Expression Processing", "chroma:document": "expressions to understand others\u2019 emotions in social interactions. The current study focuses on the fMRI responses of emo-\ntional facial expressions in the common marmoset (Callithrix jacchus), a New World primate species sharing several similar-\nities of social behavior with humans. Our results reveal that temporal and frontal face patches are involved in both basic face\ndetection and facial expression processing. The specific recruitment of these patches for negative faces associated with an\nincrease of the arousal level show that marmosets process facial expressions of their congener, vital for social communication.\nIntroduction\nSocial cognition requires the ability to perceive, process, and rec-\nognize the emotional expressions of conspecifics (Ferretti and\nPapaleo, 2019). This ability is crucial not only for humans but\nalso many other social species (Parr et al., 1998; Tate et al., 2006;\nAlbuquerque et al., 2016), allowing them to communicate inten-\ntions and to better adapt to environmental challenges (Russell,\n1997). Facial expressions are particularly necessary during social\ninteractions, constituting a powerful route of rapid nonverbal\ncommunication in all primates (Darwin, 2004).\nFunctional magnetic resonance imaging (fMRI) studies have\nidentified the neural networks underlying faces and facial\nexpression processing in humans and nonhuman primates.\nIn humans, faces elicit activity in a cortical and subcortical\nnetwork that includes the fusiform gyrus, amygdala, and fron-\ntotemporal areas in anterior and posterior regions of the supe-\nrior temporal sulcus (STS) and in the inferotemporal cortex as\nwell as the orbitofrontal cortex (Kanwisher et al., 1997; Puce et al.,\n1998; Haxby et al., 2000; Fusar-Poli et al., 2009). Distinct pat-\nterns of activation have also been associated with the process-\ning of facial expressions. Overall, the processing of emotional\nfaces is associated with increased activation in most occipito-\ntemporal face-selective regions, prefrontal and orbitofrontal"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1317
encoding: FLOAT32
metadata:
{"title": "Face-Selective Patches in Marmosets Are Involved in Dynamic and Static Facial Expression Processing", "chroma:document": "areas as well as subcortical areas including the amygdala and\ncerebellum (Kanwisher et al., 1997; Puce et al., 1998; Haxby et\nal., 2000; Blair, 2003; Murphy et al., 2003; Posamentier and\nAbdi, 2003; Strauss et al., 2005; Hennenlotter and Schroeder,\n2006; Vuilleumier and Pourtois, 2007; Fusar-Poli et al., 2009;\nReceived Aug. 2, 2022; revised Mar. 9, 2023; accepted Mar. 25, 2023.\nAuthor contributions: A.D. and S.E. designed research; A.D. and A.Z. performed research; A.D. analyzed\ndata; A.D. wrote the paper.\nSupport was provided for this research by the Canadian Institutes of Health Research (Grant FRN 148365),\nthe Canada First Research Excellence Fund to BrainsCAN, and a Discovery grant by the Natural Sciences and\nEngineering Research Council of Canada to S.E. We thank Cheryl Vander Tuin, Whitney Froese, Hannah\nPettypiece, and Miranda Bellyou for animal preparation and care; and Dr. Alex Li for scanning assistance.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Audrey Dureux at audrey.dureux@gmail.com.\nhttps://doi.org/10.1523/JNEUROSCI.1484-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, May 10, 2023 \u2022 43(19):3477\u20133494 \u2022 3477"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1318
encoding: FLOAT32
metadata:
{"title": "Intrinsic Neural Timescales in the Temporal Lobe Support an Auditory Processing Hierarchy", "chroma:document": "Behavioral/Cognitive\nIntrinsic Neural Timescales in the Temporal Lobe Support\nan Auditory Processing Hierarchy\nRiccardo Cusinato,1,2p Sigurd L. Alnes,1,2p Ellen van Maren,2 Ida Boccalaro,2 Debora Ledergerber,3\nAntoine Adamantidis,2 Lukas L. Imbach,3 Kaspar Schindler,2 Maxime O. Baud,2 and Athina Tzovara1,2,4\n1Institute of Computer Science, University of Bern, Bern 3012, Switzerland, 2Center for Experimental Neurology, Sleep Wake Epilepsy Center,\nNeuroTec, Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland, 3Swiss Epilepsy Center,\nKlinik Lengg, Zurich 8008, Switzerland, and 4Helen Wills Neuroscience Institute, University of California\u2013Berkeley, Berkeley 94720, California\nDuring rest, intrinsic neural dynamics manifest at multiple timescales, which progressively increase along visual and somato-\nsensory hierarchies. Theoretically, intrinsic timescales are thought to facilitate processing of external stimuli at multiple\nstages. However, direct links between timescales at rest and sensory processing, as well as translation to the auditory system\nare lacking. Here, we measured intracranial EEG in 11 human patients with epilepsy (4 women), while listening to pure\ntones. We show that, in the auditory network, intrinsic neural timescales progressively increase, while the spectral exponent\nflattens, from temporal to entorhinal cortex, hippocampus, and amygdala. Within the neocortex, intrinsic timescales exhibit\nspatial gradients that follow the temporal lobe anatomy. Crucially, intrinsic timescales at baseline can explain the latency of\nauditory responses: as intrinsic timescales increase, so do the single-electrode response onset and peak latencies. Our results\nsuggest that the human auditory network exhibits a repertoire of intrinsic neural dynamics, which manifest in cortical gra-\ndients with millimeter resolution and may provide a variety of temporal windows to support auditory processing."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1319
encoding: FLOAT32
metadata:
{"title": "Intrinsic Neural Timescales in the Temporal Lobe Support an Auditory Processing Hierarchy", "chroma:document": "Key words: amygdala; aperiodic activity; auditory processing; hippocampus; intracranial EEG; timescales\nSignificance Statement\nEndogenous neural dynamics are often characterized by their intrinsic timescales. These are thought to facilitate processing\nof external stimuli. However, a direct link between intrinsic timing at rest and sensory processing is missing. Here, with intra-\ncranial EEG, we show that intrinsic timescales progressively increase from temporal to entorhinal cortex, hippocampus, and\namygdala. Intrinsic timescales at baseline can explain the variability in the timing of intracranial EEG responses to sounds:\ncortical electrodes with fast timescales also show fast- and short-lasting responses to auditory stimuli, which progressively\nincrease in the hippocampus and amygdala. Our results suggest that a hierarchy of neural dynamics in the temporal lobe\nmanifests across cortical and limbic structures and can explain the temporal richness of auditory responses.\nIntroduction\nThe human brain gives rise to rich neural dynamics, which\nplay a fundamental role in processing sensory information.\nIntrinsic dynamics of the brain operate at multiple time-\nscales (Hasson et al., 2008; Honey et al., 2012; Murray et al.,\n2014; Raut et al., 2020) through oscillatory (Frauscher et al.,\n2018; Mahjoory et al., 2020; Vezoli et al., 2021) and non-\noscillatory (Gao et al., 2020) processes. In the visual and\nsomatosensory systems, intrinsic timescales manifest at\nrest, in ongoing neural activity: primary areas exhibit short\ntimescales that may facilitate a quick reaction to incoming\nstimuli (Murray et al., 2014; Siegle et al., 2021). These pro-\ngressively increase while advancing through the cortical hi-\nerarchy, supporting integration of information (Murray et\nal., 2014; Chaudhuri et al., 2015). Whether a similar hierar-\nchy of intrinsic dynamics exists in the auditory system, and\nin particular within the temporal lobe, a hub for auditory\nprocessing, remains underexplored."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1320
encoding: FLOAT32
metadata:
{"title": "Intrinsic Neural Timescales in the Temporal Lobe Support an Auditory Processing Hierarchy", "chroma:document": "Received Oct. 25, 2022; revised Feb. 21, 2023; accepted Mar. 2, 2023.\nAuthor contributions: R.C. analyzed data; R.C. and A.T. wrote the first draft of the paper; R.C., S.L.A.,\nE.v.M., I.B., D.L., A.A., L.L.I., K.S., M.O.B., and A.T. edited the paper; R.C., S.L.A., E.v.M., I.B., D.L., A.A., L.L.I.,\nK.S., M.O.B., and A.T. wrote the paper; S.L.A., I.B., A.A., and A.T. designed research; S.L.A., E.v.M., D.L., L.L.I.,\nK.S., and M.O.B. performed research.\nThis work was supported by Inselspital University Hospital Bern; the Interfaculty Research Cooperation\n\u201cDecoding Sleep: From Neurons to Health & Mind\u201d of the University of Bern to A.A., I.B., A.T., and S.L.A.;\nSwiss National Science Foundation to A.A. and 320030_188737 to A.T.; European Research Council CoG-\n725850 to A.A.; the Synapsis Foundation to A.A.; the University of Bern to A.A.; and Fondation Pierre Mercier\npour la science to A.T. We thank Prof. Johannes Sarnthein for support with recordings and feedback on the\nmanuscript.\n*R.C. and S.L.A. contributed equally to this work.\nM.O.B. holds shares with Epios SA, a medical device company based in Geneva. The remaining authors\ndeclare no competing financial interests.\nCorrespondence should be addressed to Athina Tzovara at athina.tz@gmail.com.\nhttps://doi.org/10.1523/JNEUROSCI.1941-22.2023\nCopyright \u00a9 2023 the authors\n3696 \u2022 The Journal of Neuroscience, May 17, 2023 \u2022 43(20):3696\u20133707"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1321
encoding: FLOAT32
metadata:
{"title": "From Prediction to Action: Dissociable Roles of Ventral Tegmental Area and Substantia Nigra Dopamine Neurons in Instrumental Reinforcement", "chroma:document": "Behavioral/Cognitive\nFrom Prediction to Action: Dissociable Roles of Ventral\nTegmental Area and Substantia Nigra Dopamine Neurons in\nInstrumental Reinforcement\nKurt M. Fraser,1 Heather J. Pribut,1 Patricia H. Janak,1,2,3 and\nRonald Keiflin4,5\n1Department of Psychological & Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland 21218, 2The\nSolomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, 3Kavli\nNeuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, 4Department of Psychological & Brain\nSciences, University of California, Santa Barbara, Santa Barbara, California 93106, and 5Neuroscience Research Institute, University of California\nSanta Barbara, Santa Barbara, California, 93106\nReward seeking requires the coordination of motor programs to achieve goals. Midbrain dopamine neurons are critical for\nreinforcement, and their activation is sufficient for learning about cues, actions, and outcomes. Here we examine in detail\nthe mechanisms underlying the ability of ventral tegmental area (VTA) and substantia nigra (SNc) dopamine neurons to sup-\nport instrumental learning. By exploiting numerous behavioral tasks in combination with time-limited optogenetic manipula-\ntions in male and female rats, we reveal that VTA and SNc dopamine neurons generate reinforcement through separable\npsychological processes. VTA dopamine neurons imbue actions and their associated cues with motivational value that allows\nflexible and persistent pursuit, whereas SNc dopamine neurons support time-limited, precise, action-specific learning that is\nnonscalable and inflexible. This architecture is reminiscent of actor\u2013critic reinforcement learning models with VTA and SNc\ninstructing the critic and actor, respectively. Our findings indicate that heterogeneous dopamine systems support unique"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1322
encoding: FLOAT32
metadata:
{"title": "From Prediction to Action: Dissociable Roles of Ventral Tegmental Area and Substantia Nigra Dopamine Neurons in Instrumental Reinforcement", "chroma:document": "forms of instrumental learning that ultimately result in disparate reward-seeking strategies.\nKey words: dopamine; ICSS; motivation; operant conditioning; reinforcement; reward\nSignificance Statement\nDopamine neurons in the midbrain are essential for learning, motivation, and movement. Here we describe in detail the abil-\nity of VTA and SNc dopamine neurons to generate instrumental reinforcement, a process where an agent learns about actions\nthey can emit to earn reward. While rats will avidly work and learn to respond for activation of VTA and SNc dopamine neu-\nrons, we find that only VTA dopamine neurons imbue actions and their associated cues with motivational value that spur con-\ntinued pursuit of reward. Our data support a hypothesis that VTA and SNc dopamine neurons engage distinct psychological\nprocesses that have consequences for our understanding of these neurons in health and disease.\nIntroduction\nMidbrain dopamine (DA) neurons encode reward prediction\nerrors, a fundamental parameter in reinforcement learning\n(Schultz et al., 1997; Waelti et al., 2001; Glimcher, 2011), and their\nactivation promotes learning about events leading to reward\n(Steinberg et al., 2013; Ilango et al., 2014; Ramayya et al., 2014;\nChang et al., 2016; Stauffer et al., 2016; Keiflin et al., 2019).\nAlthough early studies reported relatively broad and homogene-\nous responses to unexpected rewards across midbrain dopamine\ncell groups\u2014including the ventral tegmental area (VTA) and the\nsubstantia nigra (SNc)\u2014(Mirenowicz and Schultz, 1996; Schultz,\n1998; Bayer and Glimcher, 2005), more recent studies have dem-\nonstrated considerable heterogeneity in the response pattern of\ndifferent dopamine subsystems, particularly in relation to nonre-\nward variables (Matsumoto and Hikosaka, 2009; Barter et al.,\n2015; Lerner et al., 2015; Howe and Dombeck, 2016; Menegas et\nal., 2018; de Jong et al., 2019; Engelhard et al., 2019; Yuan et al.,\n2019). For instance, dopamine neurons in the medial VTA sig-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1323
encoding: FLOAT32
metadata:
{"title": "From Prediction to Action: Dissociable Roles of Ventral Tegmental Area and Substantia Nigra Dopamine Neurons in Instrumental Reinforcement", "chroma:document": "nal cue-related and outcome-related information, whereas do-\npamine neurons located in the lateral VTA and SNc appear to\nencode motor parameters in reward-guided tasks (Howe and\nDombeck, 2016; Engelhard et al., 2019). Moreover, these different\nReceived Jan. 3, 2023; revised Apr. 6, 2023; accepted Apr. 14, 2023.\nAuthor contributions: K.M.F., P.H.J., and R.K. designed research; K.M.F., H.J.P., and R.K. performed\nresearch; K.M.F., H.J.P., and R.K. analyzed data; K.M.F., P.H.J., and R.K. wrote the paper.\nThis research was supported by Department of Health and Human Services | National Institutes of Health |\nNational Institute on Drug Abuse Grant R01-DA-035943.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Ronald Keiflin at rkeiflin@ucsb.edu or Patricia H. Janak\natpatricia.janak@jhu.edu.\nhttps://doi.org/10.1523/JNEUROSCI.0028-23.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, May 24, 2023 \u2022 43(21):3895\u20133908 \u2022 3895"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1324
encoding: FLOAT32
metadata:
{"title": "Rapid Input-Output Transformation between Local Field Potential and Spiking Activity during Sensation but not Action in the Superior Colliculus", "chroma:document": "Systems/Circuits\nRapid Input-Output Transformation between Local Field\nPotential and Spiking Activity during Sensation but not\nAction in the Superior Colliculus\nClara Bourrelly,1,4 Corentin Massot,1,2,4 and\nNeeraj J. Gandhi1,3,4\n1Departments of Bioengineering, 2Neurobiology, 3Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, and 4Center for Neural\nBasis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15213\nSensorimotor transformation is the sequential process of registering a sensory signal in the environment and then responding\nwith the relevant movement at an appropriate time. For visually guided eye movements, neural signatures in the form of\nspiking activity of neurons have been extensively studied along the dorsoventral axis of the superior colliculus (SC). In con-\ntrast, the local field potential (LFP), which represents the putative input to a region, remains largely unexplored in the SC.\nWe therefore compared amplitude levels and onset times of both spike bursts and LFP modulations recorded simultaneously\nwith a laminar probe along the dorsoventral axis of SC in 3 male monkeys performing the visually guided delayed saccade\ntask. Both signals displayed a gradual transition from sensory activity in the superficial layers to a predominantly motor\nresponse in the deeper layers, although the transition from principally sensory to mostly motor response occurred ;500 lm\ndeeper for the LFP. For the sensory response, LFP modulation preceded spike burst onset by ,5 ms in the superficial and in-\ntermediate layers and only when data were analyzed on a trial-by-trial basis. The motor burst in the spiking activity led LFP\nmodulation by .25 ms in the deeper layers. The results reveal a fast and efficient input-output transformation between LFP\nmodulation and spike burst in the visually responsive layers activity during sensation but not during action. The spiking pat-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1325
encoding: FLOAT32
metadata:
{"title": "Rapid Input-Output Transformation between Local Field Potential and Spiking Activity during Sensation but not Action in the Superior Colliculus", "chroma:document": "tern observed during the movement phase is likely dominated by intracollicular processing that is not captured in the LFP.\nKey words: frontal eye field; local field potential; oculomotor; saccade; superior colliculus\nSignificance Statement\nWhat is the sequence of events between local field potential (LFP) modulation and spiking activity during sensorimotor trans-\nformation? A trial-by-trial analysis reveals that the LFP activity leads the spike burst in the superficial and intermediate layers\nof the superior colliculus during visual processing, while both trial-by-trial and the average analyses show that the spike burst\nleads the LFP modulation during movement generation. These results suggest an almost instantaneous LFP input, spike burst\noutput transformation in the visually responsive layers of the superior colliculus when registering the stimulus. In contrast,\nsubstantial intracollicular processing likely results in a saccade-related spike burst that leads LFP modulation.\nIntroduction\nThe orientation of gaze toward an object located in the visual\nfield results from successions of neural processing that converts\nsensory information into movement generation. Located in the\nmidbrain, the superior colliculus (SC) is an essential structure\ninvolved in this sensorimotor transformation (Sparks, 1986;\nKrauzlis, 2005; Gandhi and Katnani, 2011; Basso and May, 2017;\nSajad et al., 2020; Cooper and McPeek, 2021). Studies using sin-\ngle-channel and multichannel electrodes have shown that the SC\nis functionally organized across its dorsoventral axis, such that\nits neurons modulate their activities in response to either stimu-\nlus appearance (superficial layers), saccade generation (deeper\nlayers), or both (intermediate layers) (Mohler and Wurtz, 1976;\nIkeda et al., 2015; Massot et al., 2019). The spikes emitted by neu-\nrons, identified after high-pass filtering and thresholding of the\nneural signal, are not the only signature of neural processing.\nThe local field potential (LFP) present in the lower-frequency"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1326
encoding: FLOAT32
metadata:
{"title": "Rapid Input-Output Transformation between Local Field Potential and Spiking Activity during Sensation but not Action in the Superior Colliculus", "chroma:document": "spectrum is also informative. Whereas the spikes are the output\nof neurons, the nature of the LFP is still debated and largely\nReceived Dec. 20, 2022; revised Apr. 19, 2023; accepted Apr. 21, 2023.\nAuthor contributions: C.B., C.M., and N.J.G. designed research; C.B. and C.M. performed research; C.B.\nanalyzed data; C.B. wrote the first draft of the paper; C.B., C.M., and N.J.G. edited the paper; C.B. and N.J.G.\nwrote the paper.\nN.J.G. was supported by National Institutes of Health Grants R01 EY024831, R01 EY022854, and R21\nEY030667. The work was also supported by National Institutes of Health Core Grant P30 EY08098 to the\nDepartment of Ophthalmology. We thank the Division of Laboratory Animal Resources for veterinarian care\nand surgical assistance.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Neeraj J. Gandhi at neg8@pitt.edu or Clara Bourrelly at clb240@\npitt.edu.\nhttps://doi.org/10.1523/JNEUROSCI.2318-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, May 31, 2023 \u2022 43(22):4047\u20134061 \u2022 4047"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1327
encoding: FLOAT32
metadata:
{"title": "Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions", "chroma:document": "Systems/Circuits\nFast-Spiking Interneurons of the Premotor Cortex Contribute\nto Initiation and Execution of Spontaneous Actions\nNadia Giordano,1,2\u0001\nClaudia Alia,1\u0001 Lorenzo Fruzzetti,1,3,4 Maria Pasquini,3,4 Giulia Palla,1,2 Alberto Mazzoni,3,4\nSilvestro Micera,3,4,5 Leonardo Fogassi,6 Luca Bonini,6 and\nMatteo Caleo7,1\n1Neuroscience Institute, National Research Council (CNR), Pisa 56124, Italy, 2Scuola Normale Superiore, Pisa 56127, Italy, 3The BioRobotics\nInstitute, Scuola Superiore Sant\u2019Anna, Pontedera 56025, Italy, 4Department of Excellence in Robotics & IA, Scuola Superiore Sant\u2019Anna, Pisa 56127,\nItaly, 5Centre for Neuroprosthetics and Institute of Bioengineering, Bertarelli Foundation Chair in Translational NeuroEngineering Laboratory,\n\u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), Lausanne 1015, Switzerland, 6Department of Medicine and Surgery, University of Parma, Parma\n43125, Italy, and 7Department of Biomedical Sciences, University of Padua, Padua 35121, Italy\nPlanning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor\nand premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain\nonly partly understood. Here, we directly compared the response properties of putative pyramidal neurons (PNs) and\nGABAergic fast-spiking neurons (FSNs) during spontaneous licking and forelimb movements in male mice. Recordings cen-\ntered on the face/mouth motor field of the anterolateral motor cortex (ALM) revealed that FSNs fire longer than PNs and\nearlier for licking, but not for forelimb movements. Computational analysis revealed that FSNs carry vastly more information\nthan PNs about the onset of movement. While PNs differently modulate their discharge during distinct motor acts, most\nFSNs respond with a stereotyped increase in firing rate. Accordingly, the informational redundancy was greater among FSNs"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1328
encoding: FLOAT32
metadata:
{"title": "Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions", "chroma:document": "than PNs. Finally, optogenetic silencing of a subset of FSNs reduced spontaneous licking movement. These data suggest that\na global rise of inhibition contributes to the initiation and execution of spontaneous motor actions.\nKey words: electrophysiology; fast spiking neurons; licking; premotor cortex; pyramidal neurons; single unit activity\nSignificance Statement\nOur study contributes to clarifying the causal role of fast-spiking neurons (FSNs) in driving initiation and execution of spe-\ncific, spontaneous movements. Within the face/mouth motor field of mice premotor cortex, FSNs fire before pyramidal neu-\nrons (PNs) with a specific activation pattern: they reach their peak of activity earlier than PNs during the initiation of licking,\nbut not of forelimb, movements; duration of FSNs activity is also greater and exhibits less selectivity for the movement type,\nas compared with that of PNs. Accordingly, FSNs appear to carry more redundant information than PNs. Optogenetic silenc-\ning of FSNs reduced spontaneous licking movement, suggesting that FSNs contribute to the initiation and execution of spe-\ncific spontaneous movements, possibly by sculpting response selectivity of nearby PNs.\nIntroduction\nActivity occurring before the initiation of voluntary move-\nments is critical for action planning and execution (Weinrich\nand Wise, 1982; Godschalk et al., 1985; Wise and Mauritz,\n1985; Churchland et al., 2006; Guo et al., 2014; Murakami et\nal., 2014; Li et al., 2016; Gao et al., 2018). Specifically, premo-\ntor areas act as a conductor to orchestrate the network activity\nof the rest of the motor modules, on a moment-by-moment\nbasis, and exhibit tuning for specific movements (Georgopoulos\net al., 1982; Godschalk et al., 1985; Hocherman and Wise, 1991;\nRiehle and Requin, 1993; Messier and Kalaska, 2000;\nChurchland et al., 2006; Churchland and Shenoy, 2007). How do\ndistinct neuronal classes contribute to this process? The anticipa-\ntory activity of pyramidal neurons (PNs) has been previously"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1329
encoding: FLOAT32
metadata:
{"title": "Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions", "chroma:document": "examined (Svoboda and Li, 2018), however little is known on the\nReceived Apr. 11, 2022; revised Mar. 24, 2023; accepted Mar. 28, 2023.\nAuthor contributions: N.G., C.A., L.B., and M.C. designed research; N.G., C.A., G.P., and M.C. performed research; N.G.,\nC.A., L.Fr., M.P., G.P., and A.M. analyzed data; N.G. and C.A. wrote the first draft of the paper; N.G., C.A., L.Fr., A.M.,\nS.M., L.Fo., L.B., and M.C. edited the paper; N.G., C.A., L.Fr., L.B., and M.C. wrote the paper.\nThis project was supported by the H2020 EXCELLENT SCIENCE-European Research Council (ERC) Grant\nAgreement 692943 (BrainBIT); Regione Toscana (PERSONA Project, Bando Salute 2018); Fondazione Cassa di\nRisparmio di Padova e Rovigo (Foundation Cariparo, Project #52000; to M.C.); and the Ministry of University\n(MUR) Grant FARE2020, project n. R20NJ7BBA7 \u201cCIRCEM\u201d (to L.B.). We thank Francesca Biondi (National\nResearch Council Pisa) for excellent animal care.\nThis manuscript is dedicated to the memory of Prof. Matteo Caleo (DOD April 12, 2022), who was a model for\nenthusiasm and dedication in science and who introduced us (N.G. and C.A.) to the extraordinary world of this story.\n*N.G. and C.A. contributed equally to this work.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Claudia Alia at alia@in.cnr.it.\nhttps://doi.org/10.1523/JNEUROSCI.0750-22.2023\nCopyright \u00a9 2023 Giordano, Alia et al.\nThis is an open-access article distributed under the terms of the Creative Commons Attribution 4.0\nInternational license, which permits unrestricted use, distribution and reproduction in any medium provided\nthat the original work is properly attributed.\n4234 \u2022 The Journal of Neuroscience, June 7, 2023 \u2022 43(23):4234\u20134250"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1330
encoding: FLOAT32
metadata:
{"title": "The Differential Weights of Motivational and Task Performance Measures on Medial and Lateral Frontal Neural Activity", "chroma:document": "Behavioral/Cognitive\nThe Differential Weights of Motivational and Task\nPerformance Measures on Medial and Lateral Frontal Neural\nActivity\nCl\u00e9ment Goussi-Denjean,1 Vincent Fontanier,1 Frederic M. Stoll,2 and\nEmmanuel Procyk1\n1Inserm, Stem Cell and Brain Research Institute U1208, Universit\u00e9 Lyon 1, Bron, 69500, France and 2Nash Family Department of Neuroscience and\nFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029\nBehavioral adaptations are triggered by different constraints given by rules, and are informed by outcomes, or motivational\nchanges. Neural activity in multiple frontal areas is modulated during behavioral adaptations, but the source of these modula-\ntions and the nature of the mechanisms involved are unclear. Here we tested how different variables related to changes in\ntask performance and to behavioral adaptation impact the amplitude of event-related local field potentials (LFPs) in the lat-\neral prefrontal and midcingulate cortex of male rhesus macaques. We found that the behavioral task used induced consis-\ntently different types of performance modulation: in relation to task difficulty (imposed by the experimental setup), to\nsuccesses and errors, and to the time spent in the task. Difficulty had a significant effect on monkeys\u2019 accuracy and reaction\ntimes. Interestingly, there is also a strong interaction between difficulty and trial success on the reaction times variation.\nHowever, LFP modulations were mostly related to reaction times, touch position, feedback valence and time-in-session, with\nlittle, if any, effect of difficulty. Hence, difficulty modulated performance but not LFP activity. This suggests that, in our ex-\nperimental design, execution, regulation, and motivation-related factors are the main factors influencing medial and lateral\nfrontal activity.\nKey words: cingulate cortex; cognitive control; difficulty; electrophysiology; local field potential; monkeys\nSignificance Statement"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1331
encoding: FLOAT32
metadata:
{"title": "The Differential Weights of Motivational and Task Performance Measures on Medial and Lateral Frontal Neural Activity", "chroma:document": "Adapting decisions might be determined by several mechanisms and might be driven by motivational factors and/or factors\ninherent to the task at hand. Multiple frontal areas contribute to behavioral adaptations. One current challenge is to under-\nstand which information they process contributes to behavioral changes. Diverging views have emerged on whether task\ndemands, like the decision difficulty, or factors linked to incentives to adapt, are driving frontal activity. Here we show that\ntask difficulty had a strong effect on performance (accuracy and reaction times) but little effect on LFP recorded in monkey\nlateral prefrontal and midcingulate cortex. However, information related to actions, outcome valence, and time-in-session\nhad major influences. Thus, task difficulty modulated performance but not LFP activity in frontal areas.\nIntroduction\nAnimals adapt dynamically to external events and internal stim-\nuli to reactively or proactively improve their own state. The\nunderlying adaptive mechanisms are investigated in experimen-\ntal conditions by varying, for instance, the multiplicity of options\nto choose from, their order, the complexity of sensory informa-\ntion relevant to the task, the temporal scale over which informa-\ntion should be integrated for optimal response, or the nature of\nrewards associated to options (Chen et al., 2008; Quilodran et al.,\n2008; Kawai et al., 2015; Stoll et al., 2016a). In experimental as\nwell as in natural settings, other factors also influence behavior:\nintrinsic motivation, satiety, fatigue, boredom, etc. (Stoll et al.,\n2016b). All those factors can be reflected in performance (i.e., the\naccuracy or the speed with which task trials are solved) (Procyk\nand Goldman-Rakic, 2006; Martinez-Garcia et al., 2015).\nReceived Jan. 3, 2022; revised Feb. 17, 2023; accepted Feb. 24, 2023.\nAuthor contributions: C.G.-D., V.F., F.M.S., and E.P. analyzed data; C.G.-D. and E.P. wrote the first draft of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1332
encoding: FLOAT32
metadata:
{"title": "The Differential Weights of Motivational and Task Performance Measures on Medial and Lateral Frontal Neural Activity", "chroma:document": "the paper; C.G.-D., V.F., F.M.S., and E.P. edited the paper; C.G.-D. and E.P. wrote the paper; V.F. and F.M.S.\nperformed research; F.M.S. and E.P. designed research.\nThis work was supported by Fondation pour la Recherche M\u00e9dicale, DECCA ANR-10-SVSE4-1441 and\nNORAD ANR-19-CE37-0008-01 projects, and was performed within the framework of the LABEX CORTEX (ANR-\n11-LABX-0042) of Universit\u00e9 de Lyon operated by the French National Research Agency (ANR). E.P. is\nemployed by the Center National de la Recherche Scientifique. We thank Monkeys H, A, O, and D for their\nwork.\nThe authors declare no conflict of interest.\nCorrespondence should be addressed to Emmanuel Procyk at emmanuel.procyk@inserm.fr.\nhttps://doi.org/10.1523/JNEUROSCI.0007-22.2023\nCopyright \u00a9 2023 Goussi-Denjean et al.\nThis is an open-access article distributed under the terms of the Creative Commons Attribution 4.0\nInternational license, which permits unrestricted use, distribution and reproduction in any medium provided\nthat the original work is properly attributed.\nThe Journal of Neuroscience, June 7, 2023 \u2022 43(23):4329\u20134340 \u2022 4329"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1333
encoding: FLOAT32
metadata:
{"title": "How sex and age affect immune responses, susceptibility to infections, and response to vaccination", "chroma:document": "REVIEW\nHow sex and age affect immune responses, susceptibility to\ninfections, and response to vaccination\nCarmen Gie\ufb01ng-Kro\u00a8 ll, Peter Berger, Gu\u00a8 nter Lepperdinger\nand Beatrix Grubeck-Loebenstein\nInstitute for Biomedical Aging Research of Innsbruck University, Innsbruck,\nAustria\nSummary\nDo men die young and sick, or do women live long and healthy?\nBy trying to explain the sexual dimorphism in life expectancy,\nboth biological and environmental aspects are presently being\naddressed. Besides age-related changes, both the immune and\nthe endocrine system exhibit signi\ufb01cant sex-speci\ufb01c differences.\nThis review deals with the aging immune system and its interplay\nwith sex steroid hormones. Together, they impact on the\netiopathology of many infectious diseases, which are still the\nmajor causes of morbidity and mortality in people at old age.\nAmong men, susceptibilities toward many infectious diseases\nand the corresponding mortality rates are higher. Responses to\nvarious types of vaccination are often higher among women\nthereby also mounting stronger humoral responses. Women\nappear immune-privileged. The major sex steroid hormones\nexhibit opposing effects on cells of both the adaptive and the\ninnate immune system: estradiol being mainly enhancing, tes-\ntosterone by and large suppressive. However, levels of sex\nhormones change with age. At menopause transition, dropping\nestradiol potentially enhances immunosenescence effects posing\npostmenopausal women at additional, yet speci\ufb01c risks. Conclu-\nsively during aging, interventions, which distinctively consider\nthe changing level of individual hormones, shall provide potent\noptions in maintaining optimal immune functions.\nKey words: hormone replacement; immunosenescence; infec-\ntious diseases; menopause; sex differences; vaccination.\nIntroduction\nA paradoxical situation between aging male and female is evident in\nparticular regarding health status and the corresponding survival rates\n(Oksuzyan et al., 2008). Women exhibit signi\ufb01cantly higher life expec-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1334
encoding: FLOAT32
metadata:
{"title": "How sex and age affect immune responses, susceptibility to infections, and response to vaccination", "chroma:document": "tancies, while frequently experiencing disabilities earlier in life (Van Oyen\net al., 2013). Independent of age, death rates due to cancer, heart\ndisease, accidents, in\ufb02uenza, or pneumonia are signi\ufb01cantly higher in\nmen (Austad, 2006). Here, major contributors appear to be lifestyle\ndifferences: smoking accounts for ~60% of gender-speci\ufb01c mortality in\nEurope, alcohol abuse for ~30% (McCartney et al., 2011), followed by\nrisk-taking and seeking and complying with medical therapies (Oksuzyan\net al., 2008). Besides that, major biological determinants of the sexual\ndimorphism in longevity are X chromosome diploidy, as well as distinct\ndifferences in immune and hormone responses (Vina et al., 2005;\nAustad, 2006; Oksuzyan et al., 2008), the latter both showing consistent\nchanges with aging.\nWomen carry two X chromosomes. The X chromosome expresses\nseveral genes implicated in immunological processes, such as Toll-like\nreceptors, multiple cytokine receptors, genes involved in T-cell and B-cell\nactivity, and transcriptional and translational regulatory factors (Fish,\n2008), while in turn the Y chromosome encodes for a number of\nin\ufb02ammatory pathway genes, which are exclusively expressed in men\n(Flanagan, 2014). Most alleles on one X chromosome are randomly\nsilenced during X chromosome inactivation already during embryogen-\nesis. Polymorphism of X-linked genes and cellular mosaicism for X-linked\nparental alleles may offer additional advantages to women during host\nresponses, in particular by providing a more adaptive and balanced\ncellular machinery during innate immune responses (Spolarics, 2007;\nLibert et al., 2010). Here, we therefore reviewed the current consistent\nknowledge on aging and sex-dimorphic susceptibility to infectious\ndiseases and vaccination response in the context of changing levels of\nsex steroid hormones.\nSexual dimorphic susceptibility to infectious\ndiseases\nSex-speci\ufb01c infection and mortality rates have been documented in\nhumans (Table 1). This sexual dimorphism commences already during"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1335
encoding: FLOAT32
metadata:
{"title": "How sex and age affect immune responses, susceptibility to infections, and response to vaccination", "chroma:document": "intrauterine development, for example, a male fetus experiencing a\nchronic in\ufb02ammatory environment primarily being induced by the\nmaternal immune system in the male placenta via decidual sites yet\nalso likely due to a higher gestational infection rate of male placenta\n[(Goldenberg et al., 2006), reviewed in detail in (Clifton, 2010)]. Later in\nlife very probably due to socioeconomic behavior, such as higher\npathogen exposure during agricultural or occupational activities, men\nare more susceptible to many infections caused by viruses, bacteria,\nparasites, and fungi. They are signi\ufb01cantly more predisposed especially\nto environmental and vector-borne diseases such as leptospirosis (3.5- to\n4-fold increased incidence), schistosomiasis (1.5-fold), brucellosis, or\nrabies (Corbel, 2006; Guerra-Silveira & Abad-Franch, 2013). Albeit at\ncomparable exposure levels, men exhibit higher incidence rates for\nleishmaniasis (2.5- to 3.5-fold increased incidence), pulmonary tubercu-\nlosis (2- to 3-fold), and hepatitis A (1.4-fold), again surmising the role of\ndistinct biological differences (Guerra-Silveira & Abad-Franch, 2013).\nSimilarly, premenopausal women succumb less often to meningococcal\nor pneumococcal infections. Testosterone exerts immune suppressive\neffects thereby increasing the severity of malaria, leishmaniasis, amebi-\nasis, and tuberculosis, while at the same time supporting the clearance\nof toxoplasmosis (Bernin & Lotter, 2014; Nhamoyebonde & Leslie, 2014).\nCorrespondence\nProfessor Beatrix Grubeck-Loebenstein, Institute for Biomedical Aging Research,\nInnsbruck University, Rennweg 10, 6020 Innsbruck, Austria.\nTel.: +43 512 507 50801; fax: +43 512 507 50899;\ne-mail: beatrix.grubeck-loebenstein@uibk.ac.at\nAccepted for publication 16 December 2014\n\u00aa 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1336
encoding: FLOAT32
metadata:
{"title": "How sex and age affect immune responses, susceptibility to infections, and response to vaccination", "chroma:document": "distribution and reproduction in any medium, provided the original work is properly cited.\n309\nAging Cell (2015) 14, pp309\u2013321\nDoi: 10.1111/acel.12326\nAging\n \nCell"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1337
encoding: FLOAT32
metadata:
{"title": "Recent developments in the immunopathology of COVID-19", "chroma:document": "Allergy. 2023;78:369\u2013388. \n \n\u2003|\u2003369\nwileyonlinelibrary.com/journal/all\nReceived: 20 August 2022\u2003|\u2003Revised: 1 November 2022\u2003|\u2003Accepted: 22 November 2022\nDOI: 10.1111/all.15593  \nR E V I E W  A R T I C L E\nRecent developments in the immunopathology of COVID- 19\nHuan- ping Zhang1\n\u2003|   Yuan- li Sun2\u2003|   Yan- fen Wang3\u2003|   Duygu Yazici4\u2003|   Dilek Azkur5\n\u2003|   \nIsmail Ogulur4\u2003|   Ahmet Kursat Azkur6\n\u2003|   Zhao- wei Yang7\n\u2003|   Xiao- xue Chen1\u2003|    \nAi- Zhi Zhang8\u2003|   Jia- qian Hu2\u2003|   Guang- Hui Liu2\u2003|   M\u00fcbeccel Akdis4\n\u2003|    \nCezmi A. Akdis4\n\u2003|   Ya- dong Gao2\n1Department of Allergology, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, \nTaiyuan, China\n2Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, China\n3Department of Pediatrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, \nTaiyuan, China\n4Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland\n5Division of Pediatric Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, University of Kirikkale, Kirikkale, Turkey\n6Department of Virology, Faculty of Veterinary Medicine, University of Kirikkale, Kirikkale, Turkey\n7Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated \nHospital of Guangzhou Medical University, Guangzhou, China\n8Intensive Care Unit, The Second Hospital of Shanxi Medical University, Taiyuan, China\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction \nin any medium, provided the original work is properly cited and is not used for commercial purposes.\n\u00a9 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.\nCorrespondence"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1338
encoding: FLOAT32
metadata:
{"title": "Recent developments in the immunopathology of COVID-19", "chroma:document": "Ya- dong Gao, Department of Allergology, \nZhongnan Hospital of Wuhan University, \nDonghu Road 169, Wuhan 430071, Hubei, \nChina.\nEmail: gaoyadong@whu.edu.cn\nFunding information\nScientific Research Initiative Funds \nof Shanxi Bethune Hospital (Number: \n2020RC004).; Shanxi Medical University\nAbstract\nThere has been an important change in the clinical characteristics and immune pro-\nfile of Coronavirus disease 2019 (COVID- 19) patients during the pandemic thanks to \nthe extensive vaccination programs. Here, we highlight recent studies on COVID- 19, \nfrom the clinical and immunological characteristics to the protective and risk factors \nfor severity and mortality of COVID- 19. The efficacy of the COVID- 19 vaccines and \npotential allergic reactions after administration are also discussed. The occurrence \nof new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global \nadministration of COVID- 19 vaccines have changed the clinical scenario of COVID- 19. \nMultisystem inflammatory syndrome in children (MIS- C) may cause severe and het-\nerogeneous disease but with a lower mortality rate. Perturbations in immunity of T \ncells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming \nmay contribute to the long- term symptoms of COVID- 19. There is conflicting evidence \nabout whether atopic diseases, such as allergic asthma and rhinitis, are associated \nwith a lower susceptibility and better outcomes of COVID- 19. At the beginning of \npandemic, the European Academy of Allergy and Clinical Immunology (EAACI) de-\nveloped guidelines that provided timely information for the management of allergic \ndiseases and preventive measures to reduce transmission in the allergic clinics. The"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1339
encoding: FLOAT32
metadata:
{"title": "Huntington disease: a single-gene degenerative disorder of the striatum", "chroma:document": "C l i n i c a l  r e s e a r c h\nHuntington disease: a single-gene \ndegenerative disorder of the striatum\nPeggy C. Nopoulos, MD\nIntroduction\n Huntington disease (HD) is an autosomal domi-\nnant, neurodegenerative disorder with a primary etiolo-\ngy of corticostriatal pathology. HD is caused by a DNA \ntrinucleotide (triplet) repeat expansion of equal to or \ngreater than 40 CAG repeats within the gene Hunting-\ntin (HTT, OMIM 613004). Repeat numbers vary from \n6 to 35 in the general population. When there are less \nthan 27 repeats, there is no manifestation of HD, and \nthe gene is stable upon transmission. Repeat lengths in \nthe range of 27 to 35 also are not associated with devel-\nopment of HD; however, there is a possibility of expan-\nsion upon transmission, giving rise to the phenomenon \nof genetic anticipation. Expansion upon transmission is \nmore likely at longer repeat lengths within this range, \nand is also more likely to happen during male transmis-\nsion.1 CAG repeats in the range of 36 to 39 are of incom-\nplete penetrance with variable disease manifestation.\nPhenomenology\nHD is a rare disease with a prevalence of approximately \n10 to 12 individuals per 100 000 of European ancestry.2 \nCopyright \u00a9 2016 AICH \u2013 Servier Research Group.  All rights reserved  \n91 \nwww.dialogues-cns.org\nKeywords: Huntington disease; neurodevelopment; striatum   \nAuthor affiliations: Department of Psychiatry, University of Iowa, Iowa \nCity, Iowa, USA\nAddress for correspondence: University of Iowa, Department of Psychia-\ntry, 200 Hawkins Drive, W278 GH, Iowa City, IA 52242, USA \n(email: peggy-nopoulos@uiowa.edu)\nHuntington disease (HD) is an autosomal dominant, \nneurodegenerative disorder with a primary etiology \nof striatal pathology. The Huntingtin gene (HTT) has a \nunique feature of a DNA trinucleotide (triplet) repeat, \nwith repeat length ranging from 10 to 35 in the nor-\nmal population. Repeat lengths between 36 and 39 \ncause HD at reduced penetrance (some will get the dis-\nease, others won\u2019t) and when expanded to 40 or more"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1340
encoding: FLOAT32
metadata:
{"title": "Huntington disease: a single-gene degenerative disorder of the striatum", "chroma:document": "repeats (mHTT), causes HD at full penetrance (every \nperson with this length or beyond will definitely de-\nvelop the disease). The symptoms of HD may be motor, \ncognitive, and psychiatric, and are consistent with the \npathophysiology of frontostriatal circuitry malfunction. \nExpressed ubiquitously and throughout the entire life \ncycle (development through adulthood), mHTT causes \ninitial dysfunction and eventual death of a specific cell \npopulation within the striatum. Although all areas of \nthe brain are eventually affected, the primary pathol-\nogy of the disease is regionally specific. As a single-gene \ndisorder, HD has the distinction of having the potential \nof treatment that is aimed directly at the known patho-\ngenic mechanism by gene silencing, providing hope for \nneuroprotection and ultimately, prevention. \n\u00a9 2016, AICH \u2013 Servier Research Group \nDialogues Clin Neurosci. 2016;18:91-98."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1341
encoding: FLOAT32
metadata:
{"title": "Estrogen and Mitochondria Function in Cardiorenal Metabolic Syndrome", "chroma:document": "Estrogen and Mitochondria Function in Cardiorenal Metabolic \nSyndrome\nGuanghong Jia*,\u2020, Annayya R. Aroor*,\u2020, and James R. Sowers*,\u2020,\u2021\n*Division of Endocrinology, Diabetes, and Metabolism, Diabetes Cardiovascular Center, \nColumbia, Missouri, USA\n\u2020Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA\n\u2021Department of Medical Pharmacology and Physiology, Columbia, Missouri, USA\nAbstract\nThe cardiorenal metabolic syndrome (CRS) consists of a constellation of cardiac, renal, and \nmetabolic disorders including insulin resistance (IR), obesity, metabolic dyslipidemia, high-blood \npressure, and evidence of early cardiac and renal disease. Mitochondria dysfunction often occurs \nin the CRS, and this dysfunction is promoted by excess reactive oxygen species, genetic factors, \nIR, aging, and altered mitochondrial biogenesis. Recently, it has been shown that there are \nimportant sex-related differences in mitochondria function and metabolic, cardiovascular, and \nrenal components. Sex differences in the CRS have mainly been attributed to the estrogen\u2019s effects \nthat are mainly mediated by estrogen receptor (ER) \u03b1, ER\u03b2, and G-protein coupled receptor 30. In \nthis review, we discuss the effects of estrogen on the mitochondrial function, insulin metabolic \nsignaling, glucose transport, lipid metabolism, and inflammatory responses from liver, pancreatic \n\u03b2 cells, adipocytes, skeletal muscle, and cardiovascular tissue.\n1. INTRODUCTION\nThe cardiorenal metabolic syndrome (CRS) consists of risk factors that include \nasatherogenic dyslipidemia, elevated blood pressure, high plasma glucose, prothrombotic \ndisorder, and proinflammatory state (metabolic syndrome).1 There are a number of \nimportant bidirectional interactions among heart, kidney, brain, liver, muscle, and fat tissues, \nwhich cause a constellation of cardiac, renal, and metabolic disorders including insulin \nresistance (IR), obesity, metabolic dyslipidemia, high-blood pressure, and evidence of early"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1342
encoding: FLOAT32
metadata:
{"title": "Estrogen and Mitochondria Function in Cardiorenal Metabolic Syndrome", "chroma:document": "cardiac and renal disease (Fig. 9.1). Epidemiological studies have shown that 36.1% of adult \nmen and 32.4% of women had metabolic syndrome in the USA in 2010. This was a \nconsiderable increase from 21.8% to 23.7%, respectively, in 2002.2 The total number of \nadults with metabolic syndrome ranges from almost 77 million to almost 86 million in \nAmerica.2 The first formal definition of the metabolic syndrome was proposed by the World \nHealth Organization in 1998.3 International Diabetes Federation, American Heart \nAssociation, National Heart, Lung, and Blood Institute, World Heart Federation, \n\u00a9 2014 Elsevier Inc. All rights reserved.\nThe authors have no conflict of interest associated with this manuscript.\nNIH Public Access\nAuthor Manuscript\nProg Mol Biol Transl Sci. Author manuscript; available in PMC 2015 February 05.\nPublished in final edited form as:\nProg Mol Biol Transl Sci. 2014 ; 127: 229\u2013249. doi:10.1016/B978-0-12-394625-6.00009-X.\nNIH-PA Author Manuscript\nNIH-PA Author Manuscript\nNIH-PA Author Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1343
encoding: FLOAT32
metadata:
{"title": "Complement Activation by Adeno-Associated Virus-Neutralizing Antibody Complexes", "chroma:document": "Open camera or QR reader and\nscan code to access this article\nand other resources online.\nComplement Activation by Adeno-Associated Virus-Neutralizing\nAntibody Complexes\nCara West,1,{,{ Joel D. Federspiel,2,{ Kara Rogers,3 Arpana Khatri,1 Sheila Rao-Dayton,4 Mireia Fernandez Ocana,2\nSean Lim,5 Aaron Michael D\u2019Antona,5 Sandra Casinghino,3 and Suryanarayan Somanathan1,*\n1P\ufb01zer, Inc., Rare Disease Research Unit, Cambridge, Massachusetts, USA; 2P\ufb01zer, Inc., Drug Safety Research & Development, Andover, Massachusetts, USA;\n3P\ufb01zer, Inc., Drug Safety Research & Development, Groton, Connecticut, USA; 4P\ufb01zer, Inc., Rare Disease Research Unit, Kit Creek, North Carolina, USA; 5P\ufb01zer, Inc.,\nBiomedicine Design, Cambridge, Massachusetts, USA.\n{Current af\ufb01liation: Af\ufb01nia Therapeutics, Waltham, Massachusetts, USA.\n{These authors contributed equally to this work.\nTreatment of monogenetic disorders using vectors based on adeno-associated virus (AAV) is an area of intense interest.\nAAV is non-pathogenic human virus, and preexisting capsid antibodies are prevalent in the population posing a challenge\nto the safety and ef\ufb01cacy of AAV-mediated gene therapies. In this study, we investigated the risk of AAV-mediated\ncomplement activation when sera from a cohort of human donors were exposed to AAV9 capsid. Seropositive donor sera\ncarrying neutralizing antibodies from a previous environmental exposure activated complement when admixed with\nAAV9 capsids and complement activation was associated with donors who had higher levels of anti-AAV IgG1\nantibodies. These \ufb01ndings were consistent with mass spectrometry analysis that identi\ufb01ed increased binding of immuno-\nglobulins and complement factors when AAV9 capsids were admixed with seropositive sera. Finally, complement acti-\nvation was abrogated after IgG-depletion using af\ufb01nity columns or serum pretreatment with an IgG degrading enzyme.\nOverall, these results demonstrate an important role of preexisting neutralizing antibodies in activating complement; a risk"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1344
encoding: FLOAT32
metadata:
{"title": "Complement Activation by Adeno-Associated Virus-Neutralizing Antibody Complexes", "chroma:document": "that can be mitigated by using adequate immunosuppression strategies when dosing seropositive patients with vector.\nKeywords: AAV, complement activation, neutralizing antibodies\nINTRODUCTION\nADENO-ASSOCIATED VIRUS (AAV)-mediated gene therapy\nhas been approved to treat retinal blindness, neuromus-\ncular disorders, and dyslipidemia.1\u20133 The clinical success\nwith AAV gene therapy has led to several ongoing late-\nstage clinical trials to treat a myriad of rare monogenetic\ndisorders.4 An impediment to successful AAV gene\ntransfer is the presence of preexisting antibodies from\nwild-type AAV infection in patients.5\u20138 Antibodies thwart\nin vivo gene transfer, and transgene expression has been\nineffectual after vector administration to seropositive non-\nhuman primates (NHPs) and human subjects.9,10 Conse-\nquently, exclusion of seropositive patients with preexist-\ning antibodies above a neutralizing level (titer cutoff) has\nbeen implemented in several clinical trials. These mea-\nsures have provided bene\ufb01t by avoiding the complexities\nthat accompany vector administration to seropositive pa-\ntients. Nevertheless, there is interest in extending AAV\ngene therapies to additional patients by raising the titer\ncutoff.\nThese proposals have been bolstered by reports of sta-\nble FIX expression in a gene therapy trial that inadver-\ntently administered AAV5.FIX vector to seropositive\npatients.11 While no adverse events have been reported in\n*Correspondence: Dr. Suryanarayan Somanathan, P\ufb01zer, Inc., Rare Disease Research Unit, 1 Portland St, Cambridge, MA 02139, USA. E-mail: suryanarayan.somanathan@p\ufb01zer.com\n\u00aa Cara West et al. 2023; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://\ncreativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\n554 j\nHUMAN GENE THERAPY, VOLUME 34, NUMBERS 11 and 12\nDOI: 10.1089/hum.2023.018\nMary Ann Liebert, Inc."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1345
encoding: FLOAT32
metadata:
{"title": "Rh Prevention: A Report and Analysis of a National Programme", "chroma:document": "journal of Medical Genetics (1973).\n10, 1.\n/\nt\nI\n,)\n,\ni9/3\n/C\nRh Prevention: A Report andVnaysis'of\na National Programme\nJ. EKLUND and H. R. NEVANLINNA\nFinnish Red Cross Blood Transfusion Service, Helsinki 31, Finland\nSummary.\nA nation-wide Rh prevention programme was started in Finland in\n1969.\nBefore that, a control series of approximately 1000 Rh-negative mothers\ngiving birth to an Rh-positive child was collected to estimate the number ofmothers\nwith antibodies at either three, six, or nine months post partum.\nDuring the three-\nand-a-half year period altogether 14,980 Rh-negative patients were given 250 ,tg of\nanti-D immunoglobulin prepared from Finnish raw material in the Central Labora-\ntory of the Dutch Red Cross.\nOut of those treated before the end of June 1972,\n12,720 (97%,/) were tested four to six months post partum.\nSeventeen or 0.13%\nhad detectable antibodies; in five ofthem the infant was ABO incompatible.\nThe\nnumber ofprotected mothers with a subsequent Rh-positive infant was 1017; 10\nhad formed antibodies before the delivery of the second child.\nThe risk of primary immunization initiated during a single pregnancy was esti-\nmated to be 0.35o/.\nIn addition, there was approximately a 0 60% risk of forming\nantibodies by the next Rh-positive pregnancy.\nThe effect of prevention on the prevalence of haemolytic disease was calculated\nand compared with observed figures.\nThe preventive effect of the administration of\nanti-D\nimmunoglobulin\nis\nwell\ndocumented.\n(Combined study from Centres in England and\nBaltimore,\n1971; WHO\nScientific Group,\n1971;\nWoodrow\net al, 1971; Clarke, 1972; Clarke and\nMcConnell,\n1972.)\nThe failure incidence varies\nbetween 0 0 and 0.6% (Schneider,\n1971).\nThe\nevidence is mainly derived from comparisons with a\nlarge series of post-delivery control samples.\nThe\npossible boosting effect of an additional Rh-positive\nchild during the next pregnancy has so far only\nbeen studied in rather limited series (Woodrow,\n1970;\nSchneider,\n1971; Woodrow\net\nal,\n1971)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1346
encoding: FLOAT32
metadata:
{"title": "Rh Prevention: A Report and Analysis of a National Programme", "chroma:document": "1971).\nWith a few exceptions (Zipursky and Israels, 1967;\nGodel et al, 1968; Buchanan et al, 1969; V. J. Freda\nand J. G. Gorman in Journal of Reproductive Medi-\ncine, 1971) the reports pay little or no attention to\nthe group of patients excluded from prevention due\nto antibody formation before the delivery.\nThe purpose of this report is to present the results\nof a national Rh prevention programme including\nReceived 23 November 1972.\nmore than 12,000 patients followed up four to six\nmonths after delivery and more than 1000 of these\nwho, after the administration of anti-D immuno-\nglobulin, gave birth to another Rh-positive child.\nThe results were analysed in order to compare the\nobserved with the expected risk of immunization\nand to predict the effect of prevention on the inci-\ndence of haemolytic disease in the future.\nOther\ndetails of possible theoretical and practical impor-\ntance are discussed.\nControl Series\nThe control series comprised 1707 Rh-negative\nmothers delivered at two large lying-in hospitals in\nHelsinki between 1 October 1967 and 31 December\n1968.\nAll those without detectable antibodies at\ndelivery who gave birth to an Rh-positive child\nwere asked to give a follow up sample three, six, and\nnine months after delivery.\nThe participation rate\nwas good at 93, 90, and 85%.\nD antibodies were\nfound in 35 out of 1012 mothers, all but four of the\nantibodies being already present at three months.\n1"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1347
encoding: FLOAT32
metadata:
{"title": "An atlas of substrate specificities for the human serine threonine kinome", "chroma:document": "Nature | www.nature.com | 1\nArticle\nAn atlas of substrate specificities for the \nhuman serine/threonine kinome\nJared L. Johnson1,2,28, Tomer M. Yaron1,2,3,4,5,28, Emily M. Huntsman1,2, Alexander Kerelsky1,2,3, \nJunho Song1,2, Amit Regev1,2, Ting-Yu Lin1,2,6, Katarina Liberatore1,2, Daniel M. Cizin1,2, \nBenjamin M. Cohen1,2, Neil Vasan7,8, Yilun Ma1,2, Konstantin Krismer9,10, \nJaylissa Torres Robles11,12, Bert van de Kooij10, Anne E. van Vlimmeren10, \nNicole Andr\u00e9e-Busch13, Norbert F. K\u00e4ufer13, Maxim V. Dorovkov14, Alexey G. Ryazanov14, \nYuichiro Takagi15, Edward R. Kastenhuber1,2, Marcus D. Goncalves1,16, Benjamin D. Hopkins17, \nOlivier Elemento3,4, Dylan J. Taatjes18, Alexandre Maucuer19, Akio Yamashita20, \nAlexei Degterev21, Mohamed Uduman22, Jingyi Lu22, Sean D. Landry22, Bin Zhang22, \nIan Cossentino22, Rune Linding23, John Blenis1,24,25, Peter V. Hornbeck22, Benjamin E. Turk11\u2009\u2709, \nMichael B. Yaffe10,26,27\u2009\u2709 & Lewis C. Cantley1,2\u2009\u2709\nProtein phosphorylation is one of the most widespread post-translational \nmodifications in biology1,2. With advances in mass-spectrometry-based \nphosphoproteomics, 90,000 sites of serine and threonine phosphorylation have so  \nfar been identified, and several thousand have been associated with human diseases  \nand biological processes3,4. For the vast majority of phosphorylation events, it is not  \nyet known which of the more than 300 protein serine/threonine (Ser/Thr) kinases \nencoded in the human genome are responsible3. Here we used synthetic peptide \nlibraries to profile the substrate sequence specificity of 303 Ser/Thr kinases, comprising \nmore than 84% of those predicted to be active in humans. Viewed in its entirety, the \nsubstrate specificity of the kinome was substantially more diverse than expected and \nwas driven extensively by negative selectivity. We used our kinome-wide dataset to \ncomputationally annotate and identify the kinases capable of phosphorylating every \nreported phosphorylation site in the human Ser/Thr phosphoproteome. For the small"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1348
encoding: FLOAT32
metadata:
{"title": "An atlas of substrate specificities for the human serine threonine kinome", "chroma:document": "minority of phosphosites for which the putative protein kinases involved have been \npreviously reported, our predictions were in excellent agreement. When this approach \nwas applied to examine the signalling response of tissues and cell lines to hormones, \ngrowth factors, targeted inhibitors and environmental or genetic perturbations, it \nrevealed unexpected insights into pathway complexity and compensation. Overall, \nthese studies reveal the intrinsic substrate specificity of the human Ser/Thr kinome, \nilluminate cellular signalling responses and provide a resource to link phosphorylation \nevents to biological pathways.\nPhosphorylation of proteins at serine, threonine, tyrosine and histi-\ndine residues controls nearly every aspect of eukaryotic cellular func-\ntion1,2,5,6. Misregulation of protein kinase signalling commonly results \nin human disease7. Deciphering the cellular roles of any protein kinase \nrequires the elucidation of its downstream effector substrates. How-\never, the majority of kinase\u2013substrate relationships that have been \npublished to date involve a relatively small number of well-studied \nprotein kinases, while few, if any, substrates have been identified for \nthe majority of the approximately 300 human protein Ser/Thr kinases \nwithin the human kinome8\u201310. This lack of knowledge of kinase\u2013sub-\nstrate relationships limits the interpretation of large mass spectrometry \n(MS)-based phosphoproteomic datasets, which to date have collec-\ntively reported over 200,000 Ser and Thr phosphorylation sites on \nhuman proteins3,4,11\u201313. The specific kinases that are responsible for \nthese phosphorylation events have been reported for less than 4% \nof these sites3, substantially limiting the understanding of cellular \nphosphorylation networks.\nWell-studied Ser/Thr kinases are generally known to recognize spe-\ncific amino acid residues at multiple positions surrounding the site \nof phosphorylation14\u201317. This short linear motif, which is characteris-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1349
encoding: FLOAT32
metadata:
{"title": "An atlas of substrate specificities for the human serine threonine kinome", "chroma:document": "tic of a given protein kinase, ensures fidelity in signalling pathways \nregulating phosphorylation at a given Ser or Thr residue. Knowledge of \nkinase-recognition motifs can facilitate the discovery of new substrates, \nfor example, by scanning phosphoproteomics data for matching \nsequences. However, to date, phosphorylation-site sequence motifs are \nknown for only a subset of the human protein Ser/Thr kinome. We have \npreviously described combinatorial peptide library screening methods \nthat enable the rapid determination of specificity for individual kinases \nhttps://doi.org/10.1038/s41586-022-05575-3\nReceived: 1 May 2022\nAccepted: 17 November 2022\nPublished online: xx xx xxxx\nOpen access\n Check for updates\nA list of affiliations appears at the end of the paper."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1350
encoding: FLOAT32
metadata:
{"title": "Anti-PD-1 PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis BC infection", "chroma:document": "Anti-PD-1/PD-L1 immunotherapy in patients with solid organ \ntransplant, HIV or hepatitis B/C infection\nMartin Tioa,*, Rajat Raia, Ogochukwu M. Ezeokeb, Jennifer L. McQuadec, Lisa Zimmerd, \nChloe Khooe, John J. Parkf,g, Lavinia Spainh, Samra Turajlich,i, Luke Ardolinoj, Desmond \nYipk,l, Simone M. Goldingerm, Justine V. Cohenn, Michael Millwardo, Victoria Atkinsonp, \nAlisa Y. Kaneq,r, Paolo A. Asciertos, Claus Garbet, Ralf Gutzmeru, Douglas B. Johnsonv, \nHira A. Rizvib, Anthony M. Joshuaa,j,w, Matthew D. Hellmannb, Georgina V. Longa,x,y, \nAlexander M. Menziesa,x,y\naMelanoma Institute Australia, Sydney, Australia\nbMemorial Sloan Kettering Cancer Center, New York, USA\ncMD Anderson Cancer Center, Houston, USA\ndUniversity of Duisburg-Essen Hospital, Heidelberg, Germany\nePeter MacCallum Cancer Centre, Melbourne, Australia\nfCrown Princess Mary Cancer Centre, Sydney, Australia\ngWestmead Hospital, Sydney, Australia\nhSkin and Renal Unit, The Royal Marsden NHS Foundation Trust, London, UK\niFrancis Crick Institute, London, UK\n*Corresponding author. mtio0565@uni.sydney.edu.au (M. Tio). \nConflict of interest statement\nChloe Khoo received travel and conference support from Roche. Lisa Zimmer served a consultant for Roche, Bristol-Myers Squibb, \nMerck Sharp & Dohme, Novartis, Sanofi and Pierre Fabre; received honoraria from Roche, Bristol-Myers Squibb, Merck Sharp & \nDohme, Novartis, Merck KGaA and Pierre Fabre and support for scientific meetings from Bristol-Myers Squibb, Merck Sharp & \nDohme, Novartis, Amgen and Pierre Fabre. Michael Millward was an advisory board member for Bristol-Myers Squibb, Roche, \nAstraZeneca and Merck Sharp & Dohme. Paolo A. Ascierto served as a consultant for Bristol-Myers Squibb, Roche-Genentech, \nMerck Sharp & Dohme, Novartis, Amgen, Array, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, Medimmune, \nAstraZeneca, Syndax, Sun Pharma, Sanofy, Idera and Ultimovacs and received research funding from Bristol-Myers Squibb, Roche-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1351
encoding: FLOAT32
metadata:
{"title": "Anti-PD-1 PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis BC infection", "chroma:document": "Genentech and Array. Douglas B. Johnson was an advisory board member for Array, Bristol-Myers Squibb, Incyte and Merck and \nreceived research funding from Bristol-Myers Squibb and Incyte. Victoria Atkinson was an advisory board member for Bristol-Myers \nSquibb, Merck Sharp & Dohme, Pierre Fabre and Novartis and received travel support from Bristol-Myers Squibb and speakers fee \nfrom Merck Sharp & Dohme, Novartis and Bristol-Myers Squibb. Simone M. Goldinger was an advisory board member and received \ntravel grant support from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme and Novartis. Claus Garbe received grant support \nfrom Bristol-Myers Squibb, Novartis and Roche and personal fees from Amgen, Bristol-Myers Squibb, Novartis, Roche, Merck Sharp \n& Dohme and Philogen. Ralf Gutzmer received lecture fees from Amgen, Boehringer Ingelheim, AstraZeneca, Roche, Bristol-Myers \nSquibb, Novartis, Pierre Fabre, Merck-EMD and Almirall-Hermal; honoraria from Amgen, Leo Pharma, Inctye, Roche, Bristol-Myers \nSquibb, Novartis, Regeneron, 4SC, Pierre Fabre, Merck-EMD and Almirall-Hermal; patient fees from Amgen, Roche, Bristol-Myers \nSquibb, Novartis, Regenerom, 4SC, Philogen and Array; grant support from Novartis, Pfizer and Johnson & Johnson and support for \nscientific meetings from Roche, Bristol-Myers Squibb, Pierre Fabre. Matthew Hellman was a consultant for Bristol-Myers Squibb, \nMerck, Genentech, Roche, Astra-Zeneca, MedImmune, Novartis and Janssen and received research funding from Bristol-Myers \nSquibb. Georgina V. Long was a consultant for Array, Bristol-Myers Squibb, Novartis, Roche, Amgen, Pierre Fabre, Merck Sharp & \nDohme and Incyte. Alexander M. Menzies was an advisory board member for Merck Sharp & Dohme, Chugai, Novartis and Pierre \nFabre and received honoraria from Bristol-Myers Squibb and Novartis. All other authors report no conflicts of interest to disclose.\nWriting assistance\nNone.\nHHS Public Access\nAuthor manuscript\nEur J Cancer. Author manuscript; available in PMC 2023 May 12."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1352
encoding: FLOAT32
metadata:
{"title": "Anti-PD-1 PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis BC infection", "chroma:document": "Published in final edited form as:\nEur J Cancer. 2018 November ; 104: 137\u2013144. doi:10.1016/j.ejca.2018.09.017.\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: 1353
encoding: FLOAT32
metadata:
{"title": "Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults", "chroma:document": "The Journal of Infectious Diseases                                \nM A J O R  A R T I C L E\nvided the original work is not altered or transformed in any way, and that the work is properly \nSafety and Immunogenicity of Ad26-Vectored HIV Vaccine \nWith Mosaic Immunogens and a Novel Mosaic Envelope \nProtein in HIV-Uninfected Adults: A Phase 1/2a Study\nDaniel J. Stieh,1,a Dan H. Barouch,2,3,a Christy Comeaux,1 Michal Sarnecki,4 Kathryn E. Stephenson,2 Stephen R. Walsh,5,6 Sheetal Sawant,7\nJack Heptinstall,7 Georgia D. Tomaras,7 James G. Kublin,8 M. Juliana McElrath,8 Kristen W. Cohen,8 Stephen C. De Rosa,8 Galit Alter,3, Guido Ferrari,7\nDavid Montefiori,7 Philipp Mann,8 Steven Nijs,9 Katleen Callewaert,9 Paul A. Goepfert,10 Srilatha Edupuganti,11 Etienne Karita,12 Michael S. Seaman,2\nLawrence Corey,8 Lindsey R. Baden,6 Maria G. Pau,1 Hanneke Schuitemaker,1 and Frank Tomaka,13 on behalf of the ASCENT/HVTN118/HPX2003 Study Team\n1Janssen Vaccines and Prevention Leiden, the Netherlands; 2Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; 3Ragon Institute of MGH, MIT, and \nHarvard, Cambridge, Massachusetts, USA; 4Janssen Vaccines, Bern, Switzerland; 5Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; \n6Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA; 7Department of Surgery, Center for Human Systems Immunology, and Duke Human Vaccine Institute, Duke \nUniversity, Durham, North Carolina, USA; 8Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA; 9Janssen Research and Development, Beerse, \nBelgium; 10Division of Infectious Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; 11Division of Infectious Diseases, Department of Medicine, \nEmory University School of Medicine, Atlanta, Georgia, USA; 12Rwanda Zambia HIV Research Group, Kigali, Rwanda; and 13Janssen Research and Development, Titusville, New Jersey, USA"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1354
encoding: FLOAT32
metadata:
{"title": "Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults", "chroma:document": "Background. Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV.\nMethods. This placebo-controlled, double-blind, phase 1/2a study enrolled healthy HIV-uninfected adults at low risk for HIV \ninfection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and \nPol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade \nC regimen plus mosaic gp140), or placebo. Primary end points were safety and antibody responses.\nResults. In total 152/155 participants (clade C, n = 26; bivalent protein, n = 103; placebo, n = 26) received \u22651 injection. The \nhighest adverse event (AE) severity was grade 3 (local pain/tenderness, 12%, 2%, and 0% of the respective groups; solicited \nsystemic AEs, 19%, 15%, 0%). HIV-1 mosaic gp140-binding antibody titers were 79 595 ELISA units (EU)/mL and 137 520 EU/mL \nin the clade C and bivalent protein groups (P < .001) after dose 4 and 16 862 EU/mL and 25 162 EU/mL 6 months later. Antibody \nresponse breadth against clade C gp140 and clade C/non-clade C gp120 was highest in the bivalent protein group.\nConclusions. Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without \ncompromising safety or clade C responses.\nClinical Trials Registration. NCT02935686.\nKeywords. Ad26 HIV vaccine; broad immunogenicity; cross-clade; heterologous regimen; mosaic HIV antigen; tetravalent.\nReceived 05 July 2022; editorial decision 04 November 2022; accepted 07 November 2022; \npublished online 9 November 2022\naD. J. S. and D. H. B. contributed equally.\nPresented in part: 10th International AIDS Society Conference on HIV Science, 21\u201324 July \n2019, Mexico City, Mexico.\nCorrespondence: Daniel J. Stieh, PhD, Janssen Vaccines and Prevention, Archimedesweg 6, \nLeiden 2333, the Netherlands (dstieh@ITS.JNJ.com).\nThe Journal of Infectious Diseases\u00ae\n2023;227:939\u201350"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1355
encoding: FLOAT32
metadata:
{"title": "Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults", "chroma:document": "\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases \nSociety of America. \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution- \nNonCommercial-NoDerivs \nlicence \n(https://creativecommons.org/licenses/by-nc-nd/4.0/), \nwhich permits non-commercial reproduction and distribution of the work, in any medium, pro-\ncited. For commercial re-use, please contact journals.permissions@oup.com\nhttps://doi.org/10.1093/infdis/jiac445\nWith 38 million people living with human immunodeficien-\ncy virus (HIV) worldwide, a safe, globally effective vaccine \nremains essential to curb further HIV transmission [1]. To \ndate, 4 preventive HIV vaccine concepts have been tested \nin efficacy studies, only 1 of which demonstrated vaccine ef-\nficacy (31% in the RV144 trial) [2, 3]. The vaccines\u2019 \nimmunogens\u2019 inability to elicit a sufficiently broad and \ndurable immune response to counter the extensive diversity \nof HIV-1 is likely one of the main reasons for their poor \nefficacy [4].\nA multivalent HIV vaccine based on the replication- \nincompetent recombinant adenovirus serotype 26 (Ad26) vec-\ntor was developed using a mosaic immunogen approach to \nelicit broader responses against diverse variants of HIV-1 \n[5\u20137]. The in silico-designed mosaic antigens include a maxi-\nmum number of potential epitopes from group M variants of \nHIV-1 envelope (Env), group-specific antigen (Gag), and po-\nlymerase (Pol) proteins [8]. These Ad26-delivered HIV-1 mo-\nsaic antigens elicited broad cellular immune responses and \npartially protected against neutralization-resistant simian- \nhuman immunodeficiency virus SHIVSF162P3 in rhesus mon-\nkeys [6, 9]. Furthermore, the addition of adjuvanted recombi-\nnant glycoprotein (gp)140 to the Ad26-based mosaic vaccine \nsubstantially improved protection in rhesus monkeys [10]. \nEnv-specific binding antibodies were repeatedly identified as \na correlate of protection for these mosaic vaccines [7, 10, 11]."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1356
encoding: FLOAT32
metadata:
{"title": "Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults", "chroma:document": "ASCENT Study of Mosaic HIV Vaccine \u2022 JID 2023:227 (15 April) \u2022 939"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1357
encoding: FLOAT32
metadata:
{"title": "Sex Differences in Cognitive Impairment and Alzheimer's Disease", "chroma:document": "Sex Differences in Cognitive Impairment and Alzheimer\u2019s\nDisease\nRena Li1,* and Meharvan Singh2\n1Center for Hormone Advanced Science and Education (CHASE), Roskamp Institute, Sarasota,\nFL 34243\n2Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer\u2019s Disease\nResearch (IAADR), Center FOR HER, University of North Texas, Health Science Center, Fort\nWorth, TX 76107\nAbstract\nStudies have shown differences in specific cognitive ability domains and risk of Alzheimer\u2019s\ndisease between the men and women at later age. However it is important to know that sex\ndifferences in cognitive function during adulthood may have their basis in both organizational\neffects, i.e., occurring as early as during the neuronal development period, as well as in\nactivational effects, where the influence of the sex steroids influence brain function in adulthood.\nFurther, the rate of cognitive decline with aging is also different between the sexes. Understanding\nthe biology of sex differences in cognitive function will not only provide insight into Alzheimer\u2019s\ndisease prevention, but also is integral to the development of personalized, gender-specific\nmedicine. This review draws on epidemiological, translational, clinical, and basic science studies\nto assess the impact of sex differences in cognitive function from young to old, and examines the\neffects of sex hormone treatments on Alzheimer\u2019s disease in men and women.\n1. Introduction\nThe popular quote, \u201cMen are from Mars and women are from Venus\u201d, has been commonly\napplied to many different situations including physiology, sociology and pathology; the\ngender differences in cognitive functioning are no exception. The differences of learning and\nmemory between male and female brains are confirmed by both human and animal studies\nfrom early development stages throughout their life spans. In addition, many neurological\ndiseases exhibit gender biases, such that one sex has a greater prevalence or severity of the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1358
encoding: FLOAT32
metadata:
{"title": "Sex Differences in Cognitive Impairment and Alzheimer's Disease", "chroma:document": "disease than the other. Neurological diseases in the young and the elderly also demonstrate\ngender-specific responses to therapies. However, the question is how much, rather than\nwhether or not, the biology of sex contributes to normal cognitive function. Accordingly,\nsuch understanding may provide better insight into the factors that contribute to the risk of\n\u00a9 2014 Elsevier Inc. All rights reserved.\n*Corresponding author: Li, Rena (rli@rfdn.org), CHASE, Roskamp Institute, Sarasota, Florida, 34243, 941-752-2949 x 383.\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.\nNIH Public Access\nAuthor Manuscript\nFront Neuroendocrinol. Author manuscript; available in PMC 2015 August 01.\nPublished in final edited form as:\nFront Neuroendocrinol. 2014 August ; 35(3): 385\u2013403. doi:10.1016/j.yfrne.2014.01.002.\nNIH-PA Author Manuscript\nNIH-PA Author Manuscript\nNIH-PA Author Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1359
encoding: FLOAT32
metadata:
{"title": "Acquired Chondronecrosis", "chroma:document": "Annals ofthe Rheumatic Diseases 1990; 49: 262-264\nREVIEW ARTICLE\nAcquired chondronecrosis\nLeon Sokoloff\nAbstract\nZonal necrosis of chondrocytes is a character-\nistic feature of Kashin-Beck disease. Infer-\nences about chondronecrosis in several spon-\ntaneous and experimental arthropathies of\nother species may be relevant to the cause of\nKashin-Beck disease and conceivably, too,\nbanal osteoarthritis in man.\nAlthough it is not commonly recognised as a\ncategory of the general disease of joints, selec-\ntive necrosis of articular and growth plate\ncartilages occurs with a distinct prevalance in\nhumans and several animal species. In man the\nprototype\nis Kashin-Beck disease. Chondro-\nnecrosis in other human disorders occurs in\nmore complex circumstances. 'Laminar chon-\ndritis'\nor,\nas\nit\nis now known,\nidiopathic\nchondrolysis, was\noriginally described\nas a\nnecrosis of articular cartilage in young children.\nCell death is, however, not the definitive event.1\nNecrosis of cartilages is a feature of inherited\nadenosine deaminase deficiency. Affected infants\ndie long before locomotor disabilities are mani-\nfest.2 Death of chondrocytes is also the rule in\nochronotic cartilage.\nThe animal lesions, spontaneous and experi-\nmental, have no defined human analogues.\nNevertheless,\nthey\nshare\nseveral\nimportant\nfeatures with Kashin-Beck disease: they are\nacquired and affect growing individuals; damage\nor necrosis of articular chondrocytes leads to\nosteochondritis\ndissecans and\nosteoarthritis;\nand involvement ofgrowth plate cartilage results\nin disproportionate dwarfism and malformation\nof the skeleton. These features suggest that at\nsome early stage in the life of skeletal chondro-\ncytes the cells are particularly susceptible to\ndefined noxious agents or else have special\nmetabolic requirements.\nThis article reviews the comparative pathology\nof the several disorders and the environmental\nfactors that may be involved in their cause.\nAlthough chondrocytes are the apparent seat of\nthe disease process, the possibility that the"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1360
encoding: FLOAT32
metadata:
{"title": "Acquired Chondronecrosis", "chroma:document": "primary disturbance resides in the subchondral\nmicrocirculatory bed, and that the viability of\nthe cells is compromised as a consequence,\ncannot be dismissed out of hand; nor can the\nDepartment of\npossibility that primary changes in the pericel-\nPathology, Health\nlular matrix embarrass the nutrition of the cells.\nSciences Center,\nState University of\nNew York, Stony Brook,\nKashin-Beck disease\nNY 11794-8691, USA\nL Sokoloff\nThis non-inflammatory joint disease is widely\nprevalent in parts of northern China and neigh-\nbouring Siberia.3 Perhaps two million people\nare affected, many of them terribly crippled. In\nsome communities the prevalence is up to 85%\nof the population. All evidence indicates that\nKashin-Beck disease is of environmental origin.\nThe earliest morphological change is coagulation\nnecrosis of the deepest zone of the articular and\nepiphysial growth plate cartilages of preadoles-\ncent children. Detachment of articular cartilage\ngives rise to loose bodies later on as well as\ndeformities of multiple appendicular\njoints.\nStunting of growth at times is marked.\nDespite intensive studies by Russian, Japan-\nese, and Chinese investigators over the course of\nthe last century no toxic material has been\nidentified\nas\nresponsible\nfor\nKashin-Beck\ndisease; nor has a specially required nutritional\nfactor for the cartilages been found. There is no\nevidence for an infectious agent. Three types of\nthinking are now entertained in different re-\nsearch laboratories: (a) trace metal toxicities,\nperhaps\ncomplicating\nexcessive\nphosphate\ningestion; (b) mycotoxicosis arising from grains\ncontaminated by Fusarium oxysporum; and (c)\ndeficiency\nof\nselenium.\nThe\nincidence\nof\nKashin-Beck disease in Siberia has declined\nas food has been brought in from other areas.\nSelenium deficiency may be responsible for the\ncardiomyopathy, Keshan disease, that also is\nendemic in that part of the world, but its link\nwith Kashin-Beck disease is at best tenuous.\nOsteochondrosis\nThis term applies to one or more veterinary"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1361
encoding: FLOAT32
metadata:
{"title": "Acquired Chondronecrosis", "chroma:document": "disorders of great economic importance to the\nlivestock, kennel, and poultry industries. There\nare many reports on the subject, few of which\nare known to the medical profession.\nLike\nKashin-Beck disease, osteochondrosis occurs in\nvery young animals and has as its principal\ntarget the joint and growth plate cartilages.\nLameness, osteochondritis dissecans, stunted\ngrowth,\nand,\nultimately,\nosteoarthritis\nare\ncharacteristic of cases with advanced disease.\nThere are variations from species to species, and\nwe may be dealing with more than one entity.\nFocal failure of endochondral ossification and\nhence persistence ofnubs of basilar cartilage is a\nprominent feature of osteochondrosis in swine\nand dogs. This is often associated with necrosis\nand horizontal splitting of articular cartilage at\nthe junction of the hypertrophic and calcified\nlayers.\" The necrosis at times is sufficiently\nextensive for it to resemble Kashin-Beck disease.\n262"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1362
encoding: FLOAT32
metadata:
{"title": "Aetiology of rheumatoid arthritis: an attempt to transmit an infective agent from patients with rheumatoid arthritis to baboons", "chroma:document": "Annals of the Rheumatic Diseases, 1983, 42, 443-447\nAetiology of rheumatoid arthritis: an attempt to\ntransmit an infective agent from patients with\nrheumatoid arthritis to baboons\nJ. M. K. MacKAY,l* A. K. SIM,' J. N. McCORMICK,3 B. P. MARMION,'t\nA. P. McCRAW,' J. J. R. DUTHIE,3 AND D. L. GARDNER4\nFrom the 'Department ofBacteriology University ofEdinburgh; 'Inveresk Research International,\nMusselburgh; 'the Rheumatic Diseases Unit, Northern General Hospital, Edinburgh; and the 4Institute of\nPathology, the Queen's University of Belfast\nSUMMARY\nThirty baboons were injected intravenously and intra-articularly with material from the\njoints of 19 patients with active rheumatoid arthritis or with control material. Fifteen of the 30\nanimals received synovial fluid cells or synovial membrane cells from 3 patients with seronegative\narthritis. Ten animals received pooled cells from a total of 16 cases of seropositive arthritis. Five\nanimals were given nonrheumatoid cells. No signs of arthritis were recognised in the 27 surviving\nanimals during 3 years of observation. No significant biochemical, haematological, or serological\nchanges occurred during this period, and no gross or microscopic evidence of synovial or systemic\ndisease was found post mortem.\nThe theory that a bacterial or viral infection\nis\naetiologically related to rheumatoid arthritis (RA) is\ntenaciously held despite many false leads and the\nabsence of firm confirmatory evidence.' A variety of\nexperimental approaches in different disciplines has\nproduced candidate organisms ranging from bac-\nteria-in particular diphtheroids\"3-to mycoplasmas4'6\nand to viruses.7'-0 There is no conclusive evidence\nlinking diphtheroids or mycoplasmas to the\ndis-\nease.'-4 Similarly, a search for viruses by miscel-\nlaneous techniques has also been negative,5 though\nthere\nis\nserological\nevidence\nof\na\nrelationship\nbetween Epstein-Barr virus infection and RA.\"\nAnother way to demonstrate an infective aetiology\nfor RA is to attempt to transmit the disease to"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1363
encoding: FLOAT32
metadata:
{"title": "Aetiology of rheumatoid arthritis: an attempt to transmit an infective agent from patients with rheumatoid arthritis to baboons", "chroma:document": "experimental animals. Warren and his colleagues2-' 6\nclaim to have transmitted RA to mice, chickens and\nrats by the injection of human synovial membrane\nextracts, but other workers'7 have failed to reproduce\nthese findings. Crocker et al.,\"8 using complement-\ndeficient mice, have found that the intraperitoneal\nAccepted for publication 24 May 1982.\nCorrespondence\nto\nProfessor\nD.\nL.\nGardner,\nDepartment\nof\nHistopathology,\nUniversity Hospital of South Manchester, Nell\nLane, Withington, Manchester M20 8LR.\n*Deceased.\ntPresent address: Division of Medical Virology, Institute of Medical\nand Veterinary Science, Adelaide, South Australia.\ninjection of homogenates of RA synovial membrane\nproduces inflammatory swelling of the tails and limbs\nof mice and occasional runting. Such changes do not\nnecessarily\nindicate\ntransmission\nof an\ninfective\nagent, and as far as we can determine no confirma-\ntory reports of this observation have appeared.\nIt is recognised that the host range of certain\nhuman viruses is restricted and that negative trans-\nmission experiments with common laboratory ani-\nmals do not finally exclude the presence of a virus in\nhuman tissues. For example, human hepatitis B and\nnon-A, non-B viruses grow in chimpanzees but not in\nsmall laboratory\nanimals.\nIt\ntherefore appeared\nreasonable to attempt to transmit RA to nonhuman\nprimates. This paper describes such an attempt by the\ninoculation of human synovial cells and cell prepara-\ntions into the knee joints of baboons.\nMaterials and methods\nThirty female, immature and mature, 7*8-19*2 kg\nbaboons were imported from Africa and held at\nInveresk Research International, Edinburgh. They\nwere housed in large gang cages and kept under close\nobservation for 5 months. During this period they\nwere examined clinically at regular intervals and\nunderwent biochemical, haematological, serological,\nand\nradiological\ninvestigations.\nAll\nthe\nanimals\n443"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1364
encoding: FLOAT32
metadata:
{"title": "T-Cell Receptor Repertoire Sequencing in the Era of Cancer Immunotherapy", "chroma:document": "CLINICAL CANCER RESEARCH | REVIEW\nT-Cell Receptor Repertoire Sequencing in the Era of\nCancer Immunotherapy\nMeredith L. Frank1,2, Kaylene Lu1,2,3, Can Erdogan1,4, Yi Han5, Jian Hu2,3, Tao Wang5,6, John V. Heymach1,2,\nJianjun Zhang1,2,7, and Alexandre Reuben1,2\nABSTRACT\n\u25e5\nT cells are integral components of the adaptive immune sys-\ntem, and their responses are mediated by unique T-cell receptors\n(TCR) that recognize speci\ufb01c antigens from a variety of biological\ncontexts. As a result, analyzing the T-cell repertoire offers a better\nunderstanding of immune responses and of diseases like cancer.\nNext-generation sequencing technologies have greatly enabled\nthe high-throughput analysis of the TCR repertoire. On the basis\nof our extensive experience in the \ufb01eld from the past decade,\nwe provide an overview of TCR sequencing, from the initial\nlibrary preparation steps to sequencing and analysis methods and\n\ufb01nally to functional validation techniques. With regards to data\nanalysis, we detail important TCR repertoire metrics and present\nseveral computational tools for predicting antigen speci\ufb01city.\nFinally, we highlight important applications of TCR sequencing\nand repertoire analysis to understanding tumor biology and\ndeveloping cancer immunotherapies.\nIntroduction\nOur immune system is composed of the innate and adaptive\nimmune systems; the innate immune system protects against\ngeneral threats and conserved pathogenic sequences while the\nadaptive immune system targets and retains memory of speci\ufb01c\npathogens (1). T cells are critical mediators of adaptive immunity,\nspeci\ufb01cally driving cellular immunity as opposed to B cells that\ngovern humoral immunity. Functionally, T cells kill infected cells\nor release cytokines to recruit other immune cells after recognizing\nforeign antigens presented on infected cells (2). Immature T cells\nmigrate from hemopoietic tissues to the thymus where they mature\ninto na\u20ac\u0002ve T cells that express a unique and functional T-cell\nreceptor (TCR) that grants them the ability to recognize speci\ufb01c"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1365
encoding: FLOAT32
metadata:
{"title": "T-Cell Receptor Repertoire Sequencing in the Era of Cancer Immunotherapy", "chroma:document": "antigens (3). The thymus is also where T cells differentiate from\nan initial CD4/CD8 double-positive state into either a CD4\u00fe or\nCD8\u00fe lineage. CD4\u00fe T cells execute helper functions while CD8\u00fe\nT cells are cytotoxic (4). Na\u20ac\u0002ve T cells become antigen-experienced\nT cells after encountering their cognate antigen presented on major\nhistocompatibility complex (MHC) molecules through their TCRs.\nTCRs are highly diverse heterodimeric surface receptors that\nenable T cells to provide protection against a variety of different\npathogens. A functional TCR is comprised of two paired protein\nchains, with either alpha (a) and beta (b) chains or gamma (g) and\ndelta (d) chains (Fig. 1A). The majority of T cells express ab\nTCRs that recognize antigens presented on MHC proteins (3).\nOnly 1%\u20135% of T cells express gd TCRs, which are not MHC\nrestricted and participate in innate immune responses. It is un-\nclear which exact ligands gd T cells bind (5). For these reasons, ab\nTCRs are typically the focus of TCR sequencing and subsequent\nclinical applications.\nRegardless of type, the chains of a TCR contain an N-terminus\nvariable region capable of antigen recognition and a C-terminus\nconstant region. The variable region is assembled from variable (V),\ndiversity (D), and joining (J) gene segments through an ordered\nprocess called V(D)J recombination, in which one allele of each\ngene segment is randomly recombined with other gene segment\nalleles to form a functional antigen recognition region (Fig. 1B;\nrefs. 6, 7). TCRa and g chains are comprised of V and J gene\nsegments, while TCRb and d chains also include the D gene\nsegment, offering more diversity in structure. The overall combi-\nnatorial diversity of the gene segments is accompanied by junctional\ndiversity, which is driven by the random addition or deletion of\nnucleotides at junctions between gene segments. Both combina-\ntional and junctional diversity grant T cells a substantial range of\nantigen speci\ufb01cities, potentially accounting for 1015 to 1020 possible"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1366
encoding: FLOAT32
metadata:
{"title": "T-Cell Receptor Repertoire Sequencing in the Era of Cancer Immunotherapy", "chroma:document": "TCR chains (8). Importantly, immature T cells commit to either an\nab or gd lineage during V(D)J recombination, where the commit-\nment to ab is facilitated by the successful recombination of the\nb-chain and commitment to gd is facilitated by successful recom-\nbination of both the g and d chain (9).\nThe variable domains for each of the TCR chains have three\ncomplementarity-determining regions (CDR): CDR1, CDR2, and\nCDR3. CDR1 and CDR2, which are encoded by the V gene segment,\nprimarily facilitate the interaction between the TCR and MHC through\ncontact with the conserved a-helices of MHC. CDR3 is encoded by\nthe junction of V and J or D and J gene segments, resulting in high\n1Department of Thoracic/Head and Neck Medical Oncology, The University of\nTexas MD Anderson Cancer Center, Houston, Texas. 2The University of Texas MD\nAnderson Cancer Center UT Health Houston Graduate School of Biomedical\nSciences, Houston, Texas. 3Department of Cancer Biology, The University of\nTexas MD Anderson Cancer Center, Houston, Texas. 4Rice University, Houston,\nTexas. 5Quantitative Biomedical Research Center, Peter O\u2019Donnell Jr. School of\nPublic Health, University of Texas Southwestern Medical Center, Dallas, Texas.\n6Center for the Genetics of Host Defense, University of Texas Southwestern\nMedical Center, Dallas, Texas. 7Department of Genomic Medicine, The University\nof Texas MD Anderson Cancer Center, Houston, Texas.\nM.L. Frank and K. Lu co-wrote the manuscript.\nJ. Zhang and A. Reuben co-supervised the preparation of the manuscript.\nCorresponding Authors: Alexandre Reuben, The University of Texas MD\nAnderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.\nPhone: (713) 745-3014; E-mail: areuben@mdanderson.org; and Jianjun Zhang,\njzhang20@mdanderson.org\nClin Cancer Res 2023;29:994\u20131008\ndoi: 10.1158/1078-0432.CCR-22-2469\nThis open access article is distributed under the Creative Commons Attribution-\nNonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1367
encoding: FLOAT32
metadata:
{"title": "T-Cell Receptor Repertoire Sequencing in the Era of Cancer Immunotherapy", "chroma:document": "\u00022022 The Authors; Published by the American Association for Cancer Research\nAACRJournals.org | 994"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1368
encoding: FLOAT32
metadata:
{"title": "Intranasal Antibody Prophylaxis for Protection against Viral Disease", "chroma:document": "CLINICAL MICROBIOLOGY REVIEWS,\n0893-8512/99/$04.0010\nJuly 1999, p. 383\u2013393\nVol. 12, No. 3\nCopyright \u00a9 1999, American Society for Microbiology. All Rights Reserved.\nIntranasal Antibody Prophylaxis for Protection\nagainst Viral Disease\nRICHARD WELTZIN* AND THOMAS P. MONATH\nOraVax, Inc., Cambridge, Massachusetts 02139\nINTRODUCTION.......................................................................................................................................................383\nANTIBODY AS A MEDIATOR OF RESPIRATORY TRACT IMMUNITY.......................................................383\nRoles of Immunoglobulins G and A in Antiviral Immunity.............................................................................383\nInduction of Immunity in Respiratory Tract Lymphoid Tissue.......................................................................385\nActive versus Passive Intranasal Immunization To Prevent Human Viral Diseases....................................385\nTreatment of Established Infections....................................................................................................................386\nPASSIVE NASAL IMMUNIZATION STUDIES WITH ANIMAL MODELS OF VIRAL INFECTION........386\nIn\ufb02uenza Virus........................................................................................................................................................386\nSendai Virus ............................................................................................................................................................386\nRespiratory Syncytial Virus...................................................................................................................................387\nPASSIVE NASAL IMMUNIZATION STUDIES WITH HUMANS.....................................................................389\nImmunoglobulin Treatment...................................................................................................................................389"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1369
encoding: FLOAT32
metadata:
{"title": "Intranasal Antibody Prophylaxis for Protection against Viral Disease", "chroma:document": "Monoclonal Antibody Treatment..........................................................................................................................390\nPOTENTIAL FOR THERAPEUTIC NASAL ANTIBODY TREATMENT TO REDUCE DISEASE ..............390\nCONCLUSIONS .........................................................................................................................................................391"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1370
encoding: FLOAT32
metadata:
{"title": "Molecular Basis of the Interaction of Salmonella with the Intestinal Mucosa", "chroma:document": "CLINICAL MICROBIOLOGY REVIEWS,\n0893-8512/99/$04.0010\nJuly 1999, p. 405\u2013428\nVol. 12, No. 3\nCopyright \u00a9 1999, American Society for Microbiology. All Rights Reserved.\nMolecular Basis of the Interaction of Salmonella with the\nIntestinal Mucosa\nK. HERAN DARWIN AND VIRGINIA L. MILLER*\nDepartments of Pediatrics and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110\nINTRODUCTION.......................................................................................................................................................406\nGeneral Background on Salmonellosis................................................................................................................406\nGeneral Description of Pathogenesis...................................................................................................................406\nATTACHMENT...........................................................................................................................................................407\nType 1 Fimbriae......................................................................................................................................................410\nLong Polar Fimbriae ..............................................................................................................................................411\nPlasmid-Encoded Fimbriae ...................................................................................................................................411\nThin Aggregative Fimbriae....................................................................................................................................412\nRck ............................................................................................................................................................................412\nFunctional Redundancy?........................................................................................................................................412"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1371
encoding: FLOAT32
metadata:
{"title": "Molecular Basis of the Interaction of Salmonella with the Intestinal Mucosa", "chroma:document": "MUCOSAL INVASION..............................................................................................................................................412\nApparatus Genes.....................................................................................................................................................413\ninvH.......................................................................................................................................................................413\ninvG.......................................................................................................................................................................414\ninvE .......................................................................................................................................................................414\ninvA .......................................................................................................................................................................414\ninvB .......................................................................................................................................................................415\ninvC .......................................................................................................................................................................415\ninvI (spaM)...........................................................................................................................................................415\nspaP, spaQ, spaR (surface presentation of antigen) .......................................................................................415\nspaS .......................................................................................................................................................................415\nprgH (phoP-repressed gene)...............................................................................................................................416"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1372
encoding: FLOAT32
metadata:
{"title": "Molecular Basis of the Interaction of Salmonella with the Intestinal Mucosa", "chroma:document": "prgI and prgJ........................................................................................................................................................416\nprgK.......................................................................................................................................................................416\norgA (oxygen-regulated gene) ............................................................................................................................416\nSecreted Proteins and Their Chaperones............................................................................................................416\nSPI1-encoded secreted proteins ........................................................................................................................417\n(i) invJ (spaN) and spaO ................................................................................................................................417\n(ii) sicA (Salmonella invasion chaperone)....................................................................................................417\n(iii) sipB/sspB (Salmonella invasion protein or Salmonella secreted protein) .........................................417\n(iv) sipC/sspC ...................................................................................................................................................417\n(v) sipD/sspD ....................................................................................................................................................418\n(vi) sipA/sspA....................................................................................................................................................418\n(vii) iacP (invasion-associated acyl carrier protein)..................................................................................418\n(viii) sicP ..........................................................................................................................................................418"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1373
encoding: FLOAT32
metadata:
{"title": "Molecular Basis of the Interaction of Salmonella with the Intestinal Mucosa", "chroma:document": "(ix) sptP (secreted protein tyrosine phosphatase)......................................................................................418\n(x) avrA (avirulence).......................................................................................................................................418\nNon-SPI1-encoded proteins dependent on SPI1 for secretion .....................................................................418\n(i) sigDE/sopB (Salmonella invasion gene/Salmonella outer protein)........................................................418\n(ii) sopE ............................................................................................................................................................419\nRegulators................................................................................................................................................................419\ninvF .......................................................................................................................................................................419\nhilA-iagB ...............................................................................................................................................................420\nsirA (Salmonella invasion regulator).................................................................................................................420\nphoPQ....................................................................................................................................................................420\nOperon structure and regulation of SPI1-encoded genes .............................................................................420\nDIARRHEA..................................................................................................................................................................420"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1374
encoding: FLOAT32
metadata:
{"title": "Molecular Basis of the Interaction of Salmonella with the Intestinal Mucosa", "chroma:document": "CONCLUSIONS .........................................................................................................................................................423\nACKNOWLEDGMENTS ...........................................................................................................................................423"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1375
encoding: FLOAT32
metadata:
{"title": "Sensorimotor Alterations Induced by Novel Fentanyl Analogs in Mice: Possible Impact on Human Driving Performances", "chroma:document": "Current Neuropharmacology\n\u0002\u0003\u0003\u0004\u0005\u0006\u0007\b\t\n\u000b\u0007\b\f\r\n\u000e\u0002\u0003\u0003\u0004\u0005\u0006\u0007\u000f\t\b\u000b\u0010\u0007\f\n\u0002\u0003\u0004\u0005\u0006\u0003\u0005\n\u0007\u0005\u0006\b\t\n\u000b\n\u0004\f\r\u000e\u000f\u0010\n\u0011\u000e\u000f\u0010\u0012\u0013\u0014\n\u0015\u0016\u0015\u0017\nSend Orders for Reprints to reprints@benthamscience.net \nCurrent Neuropharmacology, 2023, 21, 87-104 \n87 \nREVIEW ARTICLE \nSensorimotor Alterations Induced by Novel Fentanyl Analogs in Mice: \nPossible Impact on Human Driving Performances \nSabrine Bilel1,#, Arianna Giorgetti2,#, Micaela Tirri1, Raffaella Arf\u00e81, Virginia Cristofori3,  \nBeatrice Marchetti1, Giorgia Corli1, Lorenzo Caruso4, Giorgio Zauli5, Raffaele Giorgetti6,\u0002 and\nMatteo Marti1,7,*,\u0002 \n1Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 \nFerrara, Italy; 2Department of Medical and Surgical Sciences, Unit of Legal Medicine, University of Bologna, Via \nIrnerio 49, 40126 Bologna, Italy; 3Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Italy; \n4Department of Environment and Prevention Sciences, University of Ferrara, Ferrara, Italy; 5Research Department, \nKing Khaled Eye Specialistic Hospital, Riyadh, Saudi Arabia; 6Department of Excellence of Biomedical Science and \nPublic Health, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy; 7Collaborative Center of the Na-\ntional Early Warning System, Department for Anti-Drug Policies, Presidency of the Council of Ministers, Ferrara, Italy \nAbstract: Operating a vehicle is a complex task that requires multiple cognitive functions and psy-\nchomotor skills to cooperate. Driving might be impaired by licit or illicit drugs, including novel psy-\nchoactive substances (NPS) and novel synthetic opioids (NSO), the effects of which are still yet to be \nelucidated in humans. In the present work, a revision of the literature regarding the psychomotor im-\npairing effects of Fentanyl (FENT) and three analogues (Acrylfentanyl, Ocfentanyl and Furanylfenta-\nnyl) is presented, as emerged by experimental studies on humans, driving under the influence of a drug"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1376
encoding: FLOAT32
metadata:
{"title": "Sensorimotor Alterations Induced by Novel Fentanyl Analogs in Mice: Possible Impact on Human Driving Performances", "chroma:document": "(DUID) and intoxication cases. An experimental study on a mouse model evaluated the sensorimotor \nalterations induced by FENT and the three fentalogs. Acute systemic administration of the four opi-\noids (0.01-15 mg/kg i.p.) dose-dependently decreased the visual object and placing tests, the acoustic \nand the tactile responses of mice. The preclinical data are in accordance with the data that emerged \nfrom the revision of the literature regarding experimental data on humans, driving under the influence \nof drugs and intoxication cases, suggesting that novel synthetic opioids might affect the psychomotor \nperformances on daily human tasks with a particular focus on driving. \nA R T I C L E  H I S T O R Y \nReceived: June 30, 2022 \nRevised: July 23, 2022 \nAccepted: August 01, 2022 \nDOI:  \n10.2174/1570159X21666221116160032\nKeywords: Acrylfentanyl, Furanylfentanyl, Ocfentanyl, naloxone, sensorimotor alterations, novel psychoactive substances, \nDUID, opioids. \n1. INTRODUCTION\nDriving under the influence of drugs (DUID) refers to the\nact of operating a vehicle following ingestion, inhalation, \nabsorption, or injection of drugs or medications other than \nalcohol, that could interfere with the capacity to drive an \nautomobile safely [1]. Driving is a complex task, where the \ndriver continuously elaborates and responds to information \nreceived from the external surroundings, and requires several \ncognitive and psychomotor functions to cooperate [2]. Many \nsubstances, both licit and illicit, may cause impairment of \ndriving performance, affecting the body and the behavior in \n*Address correspondence to this author at the Department of Translational\nMedicine, Section of Legal Medicine and LTTA Center, University of Fer-\nrara, 44121 Ferrara, Italy; Tel: +39 0532 455781; Fax: +39 0532 455777;\nE-mail: matteo.marti@unife.it\n#These authors contributed equally to the work and can be all considered\nfirst authors. \n\u0002These authors share the seniorship. \ndifferent ways. The most reported effects in cases of DUID"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1377
encoding: FLOAT32
metadata:
{"title": "Sensorimotor Alterations Induced by Novel Fentanyl Analogs in Mice: Possible Impact on Human Driving Performances", "chroma:document": "consist of impairments of psychomotor skills and cognitive \nfunctions critical to driving, including vigilance, time and \ndistance perception and monitoring, visual acuity, cognition, \njudgement and risk-taking behavior, reaction time, divided \nattention, keeping co-ordination and balance [2, 3]. A great \nalarm has been raised recently by the increase of DUID and \ntraffic accidents due to the use of drugs. Cannabis was the \nillicit drug most frequently detected in cases of DUID, fol-\nlowed by cocaine while amphetamines and illicit opioids \nwere less frequently detected. In addition to traditional sub-\nstances, novel psychoactive substances (NPS) have also been \nrelated to DUID cases. Over the period from January 2019 to \nApril 2020, 670 toxicology cases involving 46 individual NPS \nwere reported to the UNODC. Of these cases, 62% were clas-\nsified as DUID [4]. Synthetic cathinones are the most fre-\nquently detected NPS in Europe together with synthetic can-\nnabinoids. However, the reports regarding the involvement \n1875-6190/23\n\u00a9 2023  Bentham Science Publishers\nThis is an Open Access article  published \nunder CC BY 4.0  \nhttps://creativecommons.org/licenses/\nby/4.0/legalcode"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1378
encoding: FLOAT32
metadata:
{"title": "Selecting the Best Animal Model of Parkinson's Disease for Your Research Purpose: Insight from in vivo PET Imaging Studies", "chroma:document": "Current Neuropharmacology\n\u0002\u0003\u0003\u0004\u0005\u0006\u0007\b\t\n\u000b\u0007\b\f\r\n\u000e\u0002\u0003\u0003\u0004\u0005\u0006\u0007\u000f\t\b\u000b\u0010\u0007\f\n\u0002\u0003\u0004\u0005\u0006\u0003\u0005\n\u0007\u0005\u0006\b\t\n\u000b\n\u0004\f\r\u000e\u000f\u0010\n\u0011\u000e\u000f\u0010\u0012\u0013\u0014\n\u0015\u0016\u0015\u0017\nSend Orders for Reprints to reprints@benthamscience.net \n \nCurrent Neuropharmacology, 2023, 21, 1241-1272 \n1241 \nREVIEW ARTICLE \nSelecting the Best Animal Model of Parkinson\u2019s Disease for Your Research \nPurpose: Insight from in vivo PET Imaging Studies \n \nCaroline Cristiano Real1,2, Karina Henrique Binda1,2, Majken Borup Thomsen1,2,  \nThea Pinholt Lillethorup1,2, David James Brooks1,3 and Anne Marlene Landau1,2,* \n1Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; 2Translational Neu-\nropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Institute of Translational \nand Clinical Research, University of Newcastle, Upon Tyne, UK \n \nAbstract: Parkinson\u2019s disease (PD) is a debilitating neurodegenerative multisystem disorder lead-\ning to motor and non-motor symptoms in millions of individuals. Despite intense research, there is \nstill no cure, and early disease biomarkers are lacking. Animal models of PD have been inspired by \nbasic elements of its pathogenesis, such as dopamine dysfunction, alpha-synuclein accumulation, \nneuroinflammation and disruption of protein degradation, and these have been crucial for a deeper \nunderstanding of the mechanisms of pathology, the identification of biomarkers, and evaluation of \nnovel therapies. Imaging biomarkers are non-invasive tools to assess disease progression and re-\nsponse to therapies; their discovery and validation have been an active field of translational re-\nsearch. Here, we highlight different considerations of animal models of PD that can be applied to \nfuture research, in terms of their suitability to answer different research questions. We provide the \nreader with important considerations of the best choice of model to use based on the disease fea-\ntures of each model, including issues related to different species. In addition, positron emission to-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1379
encoding: FLOAT32
metadata:
{"title": "Selecting the Best Animal Model of Parkinson's Disease for Your Research Purpose: Insight from in vivo PET Imaging Studies", "chroma:document": "mography studies conducted in PD animal models in the last 5 years are presented. With a variety \nof different species, interventions and genetic information, the choice of the most appropriate model \nto answer research questions can be daunting, especially since no single model recapitulates all as-\npects of this complex disorder. Appropriate animal models in conjunction with in vivo molecular \nimaging tools, if selected properly, can be a powerful combination for the assessment of novel ther-\napies and developing tools for early diagnosis. \n \nA R T I C L E  H I S T O R Y \n \nReceived: August 17, 2022 \nRevised: September 08, 2022 \nAccepted: September 08, 2022 \n \nDOI:  \n10.2174/1570159X21666230216101659 \n \nKeywords: Animal models, Parkinson\u2019s disease, rodent, non-human primate, minipig, alpha-synuclein, positron emission to-\nmography, autoradiography.  \n1. INTRODUCTION \n \nParkinson\u2019s disease (PD) is an age-related progressive \nneurodegenerative disorder characterized by neuronal and \nneuritic accumulation of misfolded and aggregated alpha-\nsynuclein (\u03b1-syn) containing inclusions called Lewy bodies \nand Lewy neurites in brain regions targeting the substantia \nnigra pars compacta (SNpc) and also peripheral organs. Loss \nof dopaminergic neurons in the SNpc causes a reduction in \navailable dopamine (DA) in the striatum, which affects sig-\nnalling to the motor cortex and initiates the most characteris-\ntic clinical symptoms of PD, namely limb bradykinesia in \ncombination with rigidity and/or rest tremor [1, 2]. The \nspread of \u03b1-syn inclusions and neurodegeneration affect not \n \n*Address correspondence to this author at the Translational Neuropsychiatry \nUnit, Department of Clinical Medicine, Aarhus University Hospital, A701 - \nPalle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark; Tel: +45 \n50209259; E-mail: alandau@clin.au.dk  \nonly the dopaminergic system but also the serotonergic, nor-\nadrenergic and cholinergic systems. These are responsible \nfor the non-motor features of PD, including sleep, autonomic"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1380
encoding: FLOAT32
metadata:
{"title": "Selecting the Best Animal Model of Parkinson's Disease for Your Research Purpose: Insight from in vivo PET Imaging Studies", "chroma:document": "and psychiatric dysfunctions, such as insomnia, rapid eye \nmovement (REM), sleep behaviour disorder (RBD), consti-\npation, depression, and hyposmia [2]. The development of \nthe non-motor features can occur both prodromally and at a \nlater stage of PD. Failure to clear \u03b1-syn or its overexpression, \nmisfolding, aggregation and propagation is the underlying \nmechanism driving Lewy body disorders; this molecular \npathogenesis also leads to altered mitochondrial function, \noxidative stress, and neuroinflammation/glial activation. \nWhile age is the greatest risk factor for PD, multiple aspects \nhave been suggested to play a role in the aetiology of PD, \nincluding inflammation, gut microbiome composition [3, 4], \nand exposure to environmental factors, including infection, \npesticides and air pollution [5, 6]. The majority of PD cases \nare idiopathic though 5-40% have a genetic origin depending \n1875-6190/23 $65.00+.00\n\u00a9 2023 Bentham Science Publishers"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1381
encoding: FLOAT32
metadata:
{"title": "Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19", "chroma:document": "Drug Repurposing and Observational Studies: The Case of Antivirals\nfor the Treatment of COVID-19\nMiguel A. Hern\u00e1n, MD; and Julia del Amo, MD\nRemdesivir and molnupiravir were the only 2 repurposed antivi-\nrals that were approved for emergency use during the COVID-19\npandemic. Both drugs received their emergency use authorization\non the basis of a single industry-funded phase 3 trial, which was\nlaunched after evidence of in vitro activity against SARS-CoV-2. In\ncontrast, for tenofovir disoproxil fumarate (TDF), little in vitro evi-\ndence was generated, no randomized trials for early treatment\nwere done, and the drug was not considered for authorization.\nYet, by the summer of 2020, observational evidence suggested a\nsubstantially lower risk for severe COVID-19 in TDF users\ncompared with nonusers. The decision-making process for\nthe launching of randomized trials for these 3 drugs is reviewed.\nObservational data in favor of TDF was systematically dismissed,\neven though no viable alternative explanations were proposed\nfor the lower risk for severe COVID-19 among TDF users.\nLessons learned from the TDF example during the \ufb01rst 2 years\nof the COVID-19 pandemic are described, and the use of\nobservational clinical data to guide decisions about the launch\nof randomized trials during the next public health emergency is\nproposed. The goal is that gatekeepers of randomized trials\nmake better use of the available observational evidence for the\nrepurposing of drugs without commercial value.\nAnn Intern Med. doi:10.7326/M22-3582\nAnnals.org\nFor author, article, and disclosure information, see end of text.\nThis article was published at Annals.org on 28 March 2023.\nW\nhen seeking to repurpose drugs to treat a new\ndisease, deciding which compounds graduate to\nrandomized trials typically relies on preclinical evidence:\nIn silico mathematical models and in vitro studies in bio-\nlogical samples are followed by in vivo animal experi-\nments before human trials. What if observational studies"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1382
encoding: FLOAT32
metadata:
{"title": "Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19", "chroma:document": "show that users of a drug have better outcomes after\nacquiring the new disease? Should this information inform\nthe launch of human trials?\nWe review the decision-making process for 3 drugs\nconsidered for repurposing for COVID-19: remdesivir,\nmolnupiravir, and tenofovir. Remdesivir and molnupiravir\nwere the only 2 repurposed antivirals that were approved\nfor emergency use. Both were studied in randomized tri-\nals. Tenofovir, with observational evidence suggesting\nfavorable COVID-19 outcomes, was not adequately stud-\nied in trials and never received emergency use approval.\nUsing these case studies, we make proposals to help\nmake better use of the available observational evidence\nduring the next public health emergency.\nWHY DID REMDESIVIR MAKE IT INTO\nRANDOMIZED TRIALS?\nRemdesivir, developed by Gilead Sciences and studied\nas a potential treatment of Ebola virus infection, received\nU.S. Food and Drug Administration emergency use au-\nthorization on 1 May 2020 for in-hospital treatment of\nCOVID-19. At that time, the only randomized trial avail-\nable had reported quicker recovery and lower mortality\nwith remdesivir versus placebo (1). Three additional trials\ndone in 2020 and 2021 reported no or a modest survival\nbene\ufb01t with remdesivir in hospitalized patients (2\u20134).\nRemdesivir, an intravenous and expensive drug, had\nbeen prioritized for randomized trials by the World\nHealth Organization Scienti\ufb01c Advisory Group on the ba-\nsis of its broad antiviral spectrum, the available in vitro\nand in vivo data available, and the clinical safety data (5).\nYet, many antivirals have broad spectrum, the in vivo evi-\ndence was indirect (activity against Middle East respiratory\nsyndrome\u2013CoV and SARS-CoV), and remdesivir had a\nshort safety record compared with other antivirals. These\nrecommendations encouraged randomized trials of remde-\nsivir, such as the 4-group Solidarity trial, which studied\nremdesivir, lopinavir\u2013ritonavir, hydroxychloroquine, and\ninterferon (2). The last 3 groups were abandoned because"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1383
encoding: FLOAT32
metadata:
{"title": "Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19", "chroma:document": "of ineffectiveness. Because the repurposing recommen-\ndations were based on weak evidence, it is unlikely that\nthe World Health Organization experts could have made\nbetter recommendations in March 2020.\nThe disappointing results of these remdesivir trials\nwere partly explained by the focus on hospitalized patients\nbecause antivirals are expected to be more effective as\ntreatment in earlier stages of the infection (when viral repli-\ncation, not in\ufb02ammation, is the predominant pathologic\nprocess) or prophylaxis. In fact, remdesivir had a clinical\nbene\ufb01t in monkeys treated within hours of SARS-CoV-2\ninfection (6), and a randomized trial in nonhospitalized\nhigh-risk humans with COVID-19 published in December\n2021 found an 87% lower risk for hospitalization for remde-\nsivir versus placebo (7). Nevertheless, remdesivir did not\nbecome the treatment of choice in ambulatory settings\nbecause of the availability of oral alternatives that were per-\nceived to be more effective.\nWHY DID MOLNUPIRAVIR MAKE INTO\nRANDOMIZED TRIALS?\nMolnupiravir was developed at Emory University with\nfunding from the National Institute of Allergy and Infectious\nDiseases and Defense Threat Reduction Agency. While in\npreclinical development for in\ufb02uenza treatment, molnupira-\nvir was reported to inhibit SARS-CoV-2 in vitro (8) and block\nSARS-CoV-2 transmission in ferrets (9). On 23 March 2020,\nEmory University sold an exclusive license to Ridgeback\nBiotherapeutics to conduct randomized trials of molnupira-\nvir for COVID-19 (10). After the Biomedical Advanced\nResearch and Development Authority declined to fund\nthese trials (11), Merck acquired the rights to molnupira-\nvir and launched 2 phase 2 randomized trials in October\nAnnals.org\nAnnals of Internal Medicine \u00a9 2023 American College of Physicians 1\nAnnals of Internal Medicine\nMEDICINE AND PUBLIC ISSUES"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1384
encoding: FLOAT32
metadata:
{"title": "Editorial Sir Cyril Clarke and Journal of Medical Genetics: an appreciation", "chroma:document": "Editorial\nJournal of Medical Genetics, 1985, 22, 417\nSir Cyril Clarke and Journal of Medical Genetics: an appreciation\nFrom its first issue in September 1964 until August this year - a span of 21 years - the Journal of\nMedical Genetics has had only two editors, Arnold Sorsby and Sir Cyril Clarke. Fifteen of these\nyears have been under Sir Cyril's editorship, a time during which the Journal has grown steadily\nboth in reputation and in size. A glance through the contents pages of these years shows how\nmany landmarks in the field had their first publication in the Journal, as well as how many young\ncontributors to the early issues now hold distinguished positions throughout the world.\nFrom its inception, the role of Journal ofMedical Genetics was seen as a unifying one, bringing\ntogether under a single cover work on all aspects of Medical Genetics which, even at that time,\nwas scattered and often inaccessible. That the Journal should have maintained and strengthened\nthis role, giving its readers both a high scientific standard and a high degree of clinical interest, is\na formidable achievement, and one of which Sir Cyril can justly be proud.\nThis issue marks Sir Cyril's retirement from the editorship by a collection of papers which\ndiffers somewhat from the usual form of 'festschrift'. The contributions come from those who\nworked with him as colleagues in Liverpool over varying periods, and whose present work and\ninterests cover - as can be seen from the papers - a wide variety of fields. Contributors were\nasked for a paper that reflected their own current work, rather than attempting to select a single\ntheme;\nas an acknowledgement to a person whose own work and interests have ranged\nexceptionally widely in both Medical and basic Genetics, this is perhaps appropriate.\nWhile most people will associate Sir Cyril's name with his work on the prevention of Rhesus\nhaemolytic disease, his studies on inherited oesophageal cancer, on genetic linkage in man, on"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1385
encoding: FLOAT32
metadata:
{"title": "Editorial Sir Cyril Clarke and Journal of Medical Genetics: an appreciation", "chroma:document": "ABO blood group associations, as well as his research on the genetic control of mimicry in the\ngenus Papilio, are but a few examples of his original talent.\nSome of Sir Cyril's colleagues, notably Phillip Sheppard, are sadly no longer living to\ncontribute, while Stanley Walker's death occurred shortly after completing his paper for this\nissue. Not all the contributors are currently working in Medical Genetics departments, a fact that\nperhaps reflects Sir Cyril's own view that Medical Genetics should be a subject that permeates\nand influences the whole of medicine, rather than develop in isolation. Finally, the contribution\nfrom Victor McKusick emphasises the close and fruitful link over many years that resulted in a\nsuccession of young workers (myself included) travelling between Liverpool and Baltimore to\ngain further experience in a still embryonic specialty.\nThe Journal of Medical Genetics and its readers wish Sir Cyril and his wife Feo a long, happy,\nand active retirement.\nPETER S HARPER\n417"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1386
encoding: FLOAT32
metadata:
{"title": "Genetical Components of Physiological Tremor", "chroma:document": "Journal of Medical Genetics (1975).\n12, 162.\nGenetical components of physiological tremor\nP. J. TYRER* and JUDITH KASRIELt\nSummary.\nPhysiological tremor was measured in 14 pairs of monozygotic\ntwins, 14 pairs of dizygotic twins, and 14 pairs of control subjects matched for age\nand sex.\nPostural finger tremor was measured in each pair using a sub-miniature\naccelerometer and subjecting the amplified signals to power spectral analysis.\nSig-\nnificant genetical influences were found for the proportion oftremor at frequencies\nnear the peak frequency of9-10 Hz.\nNo genetical effects were found at other fre-\nquencies or for the absolute amount of tremor.\nThe results suggest that physio-\nlogical tremor between 8 and 13 Hz is genetically influenced and that tremor at\nthese frequencies is determined by different mechanisms than those at other fre-\nquencies.\nAlthough tremor has been studied scientifically\nfor over a century (Ferrand, 1868), we are still not\ncertain how normal physiological tremor is caused\nand how it is maintained.\nThe evidence that we\nhave is conflicting but it appears that such tremor is\nthe resultant of several different mechanisms. They\ninclude\n'hunting'\nin the servo-loop between\na\nstretch stimulus and reflex corrective muscular\naction (Halliday and Redfearn,\n1956; Lippold,\nRedfearn, and Vuco, 1957; Lippold, 1970a), ballisto-\ncardiographic\neffects transmitted passively from\ncardiorespiratory\nforces\n(Brumlik,\n1962;\nVan\nBuskirk and Fink, 1962; Yap and Boshes, 1967), and\nmechanical influences, particularly at higher fre-\nquencies of tremor (Stiles and Randall, 1967).\nOne\nconsistent feature of physiological tremor is the pre-\nsence of a main peak at or near 9 Hz which persists\nunder a wide range of experimental conditions\n(Sutton and Sykes, 1967).\nThe relationship be-\ntween tremor near the peak frequency and that at\nother frequencies has also been disputed; some\nworkers have suggested that fast and slow physio-\nlogical tremors are harmonics of the peak frequency\nof tremor (Merton, Morton, and Rashbass, 1967)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1387
encoding: FLOAT32
metadata:
{"title": "Genetical Components of Physiological Tremor", "chroma:document": "In view of the uncertainty about the origins of\nthe different frequencies of physiological tremor\nit is surprising that there have been no genetical\nstudies of the phenomenon.\nEssential or heredo-\nfamilial tremor, which appears to be qualitatively\nsimilar to physiological tremor but exaggerated\nin degree (Marshall, 1962), has long been known\nto be influenced strongly by genetical factors (Dana,\n1887; Critchley, 1949; Larsson and Sjogren, 1960)\nbut even in this condition the precise nature of the\ngenetical components is unclear.\nGenetical investigations have potential value in\nelucidating many of the unanswered questions\nposed by these studies, not the least of which is the\nrelationship\nbetween\ntremor\nand\nthe\nelectro-\nencephalogram (EEG).\nLippold (1970b; 1973) has\nprovided\nstrong evidence, which although\ndis-\nputed has yet to be explained, that the alpha rhythm\nis an artifact produced by tremor ofthe extra-ocular\nmuscles.\nAs the alpha rhythm is genetically in-\nfluenced (Lennox, Gibbs, and Gibbs, 1945; Young,\nLader, and Fenton,\n1972) physiological tremor\nwould have to be similarly influenced if it was the\ncause of the alpha rhythm.\nMethod\nFourteen pairs ofmonozygotic (MZ) twins, 14 pairs of\ndizygotic (DZ) twins, and 14 pairs ofcontrols, aged 17-44\n(mean 24.1 years) were investigated.\nAll the twins were\ncontacted through the Medical Research Council Twin\nRegister at the Institute ofPsychiatry, apart from the two\nauthors and their co-twins.\nAll measurements oftremor\nwere made by P.J.T. who was unaware of the zygosity\nof the twins until the end of the study.\nJ.K. selected\nthe twins so that there were 14 pairs of supposed or pre-\nviously confirmed monozygotic and dizygotic twins with\n162\nReceived 22 May 1974.\n* Department of Psychiatry, University of Southampton, South\nAcademic Block, Southampton General Hospital, Tremona Road,\nSouthampton S09 4XY.\nt Institute of Psychiatry, De Crespigny Park, London SE5 8AF."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1388
encoding: FLOAT32
metadata:
{"title": "Central retinal artery occlusion (reversible) in sickle trait with glaucoma", "chroma:document": "Brit. J. Ophthal. (1976) 60, 428\nCentral retinal artery occlusion (reversible) in\nsickle trait with glaucoma\nRONALD L. RADIUS AND DANIEL FINKELSTEIN\nFrom the Wilmer Ophthalmological Institute, The Johns Hopkins University\nand Hospital, Baltimore, Maryland, USA\nRetinal vascular occlusions of several types occur\nin the various sickle haemoglobin disorders (SS,\nSA, SC, S-Thal) (Edington and\nSarkies,\nI952;\nHenry\nand\nChapman,\n1954;\nGoldberg,\n197Ia;\nKennedy and Cope,\nI958;\nIsbey,\nClifford, and\nTanaka,\nI958;\nLieb,\nGeeraets,\nand\nGuerry,\nI959). Occlusions\nare primarily of small vessels\nin the peripheral retina preceding the development\nof neovascularization (Welch and Goldberg, I966;\nGoldberg,\n197Ia, b). Occlusions of small vessels\nin the macula have also been reported in SS and\nSC\nhaemoglobinopathy\n(Knapp,\nI972;\nAcacio\nand\nGoldberg,\nI973;\nRyan,\n1974).\nThey\nare\nprobably due\nto intravascular emboli of sickled\nred\nblood\ncells\n(Welch\nand\nGoldberg,\nI966;\nGoldberg,\nI97ia, b).\nFactors known\nto enhance\nsickling\nof\nred\ncells\nthereby\ninfluencing\nthe\nrisk\nof\nvascular\nthrombosis\ninclude\nhypoxia,\ndehydration,\nlowered\npH,\nand\nhyperviscosity\n(Sherman, I940; Griggs and Harris, 1956; Perillie\nand Epstein, I962; Charache and Conley, I964).\nNot surprisingly, therefore, under certain condi-\ntions occlusion of large vessels such as the central\nretinal artery occur (Kabakow, Van Wiemokly, and\nLyons,\nI955;\nConrad and Penner,\nI967;\nStein\nand\nGay,\nI970;\nMichelson\nand\nPfaffenbach,\nI972). We report a case of central retinal artery\nocclusion in SA disease immediately after diuretic\nand\nhyperosmotic\ntherapy\nfor\nacute\ntraumatic\nglaucoma. We believe that this treatment must be\nused cautiously in the sickle patient whose ocular\ncirculation\nis\nalready\ncompromised\nby\nacute\nglaucoma.\nCase report\nAn i8-year-old black woman presented to the Wilmer\nemergency room with a traumatic hyphaema 24 hours\nafter a blunt ocular injury. Her medical and family\nhistory were unremarkable. Uncorrected visual acuity\nwas light perception\nright\neye, 20/20\nleft\neye. The"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1389
encoding: FLOAT32
metadata:
{"title": "Central retinal artery occlusion (reversible) in sickle trait with glaucoma", "chroma:document": "eye. The\nAddress for reprints: D. Finkelstein, MD, The Wilmer Ophthal-\nmological\nInstitute,\nJohns\nHopkins\nUniversity\nand\nHospital,\nBaltimore, Maryland 21205, USA\nanterior chamber contained diffuse haemorrhage with\na layered hyphaema\nof about\nio per\ncent.\nOcular\nmotility was normal. Intraocular pressure by applanation\nwas 55 mmHg. The fundus could not be visualized\nthrough the anterior chamber blood. Examination of\nthe left eye was normal in all respects.\nTreatment consisted of atropine cycloplegia, topical\ndexamethasone,\nand\nI 20 ml\nglycerol\n75\nper\ncent.\nEmesis followed shortly after osmotic therapy. Intra-\nocular pressure remained raised at 55 mmHg. Subse-\nquent treatment consisted of intravenous acetazolamide\n500 mg and mannitol I00 g (1-5 g/kg) at an infusion\nrate of 5 g/minute. One hour later ocular tension was\n55 mmHg. Vision in the right eye was no light percep-\ntion when tested with the American optical indirect\nophthalmoscope at maximum voltage.\nThe\nclinical impression was that the patient had\nsuffered a central retinal artery occlusion. An anterior\nchamber paracentesis of o-o8 ml was performed. After\nthis vision returned to brisk light perception.\nIntra-\nocular pressure was subsequently controlled with oral\nacetazolamide. With clearing of the ocular haemorrhage\nfundus examination showed disc hyperaemia. Fluores-\ncein angiography was essentially unremarkable. Elec-\ntroretinography could not be performed. Subsequent\nserum\nelectrophoresis\nshowed\nsickle-cell\ntrait\n(SA)\nhaemoglobinopathy with 42 per cent sickle-cell haemo-\nglobin. Visual acuity returned to the 20/30 level.\nDiscussion\nOur patient presented with an intraocular pressure\nof 55 mmHg and brisk light perception vision.\nOne hour after diuretic and osmotic therapy the\npressure remained\nat 55 mmHg with no\nlight\nperception.\nThis\ntime\nsequence\nsuggests\nthat\nincreased intravascular tonicity and altered haemo-\ndynamics after these medications may have pre-\ncipitated an occlusion in an already compromised\nvascular system. Intravenous infusion of mannitol"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1390
encoding: FLOAT32
metadata:
{"title": "Central retinal artery occlusion (reversible) in sickle trait with glaucoma", "chroma:document": "is\nknown\nto\nincrease\nserum\nosmolarity\nfrom\nIo-40 mosm/l depending on rate of infusion and\ndosage\n(Galin,\nDavidson, and Pasmanik,\nI963;\nWeiss and Wise, I962; Kolker and Hetherington,\n1970).\nIncreased serum\ntonicity\noccurs\nrapidly\nthroughout the infusion and returns to equilibrium"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1391
encoding: FLOAT32
metadata:
{"title": "Ocular motor dysfunction in total and hemicerebellectomized monkeys", "chroma:document": "Brit. 7. Ophthal. (I975) 59, 560\nOcular motor dysfunction in total and\nhemicerebellectomized monkeys\nRONALD M. BURDE, MALCOLM H. STROUD, G. ROPER-HALL,\nFREMONT P. WIRTH, AND JAMES L. O'LEARY*\nFrom the Departments of Ophthalmology, Otolaryngology, Neurology and Neurosurgery, Washington\nUniversity School of Medicine, St Louis, Missouri, USA\nRecent reports (Kornhuber, 1971; Robinson, I974;\nWestheimer and Blair,\n1973) have implied con-\nflicting roles for the cerebellum in the control of eye\nmovements. Recently, as part of a large multispecies\nstudy to determine the effects of cerebellectomy on\npower\nand\nco-ordinating functions (Wirth\nand\nO'Leary, 1974), we had the opportunity to study\nprospectively the effects of this surgery on the ocular\nmotor system in primates. Altogether 2I monkeys\n(Macaque mullata) were observed both during the\nacute stage (the first postoperative 8 weeks) and\nduring the compensated stage (as late as 6 months\nafter surgery). Our observations\non the\nocular\nmotor function of these primates are reported in\nthis paper and an attempt is made to draw some\npathophysiological correlations with human ocular\nmotor dysfunction.\nMaterial and methods\nThe details of animal preparation have been reported\nseparately (Wirth and O'Leary, 1974). The extent of\ncerebellar removal was confirmed in each animal with a\nthorough neuroanatomical study at the conclusion of\neach experiment. These findings are also reported in\ndetail elsewhere (Wirth and O'Leary, I974) and will be\nreferred to here only when relevant to specific ocular\nmovement disorders.\nThe animals were studied in a primate chair with or\nwithout head restraint. Motion pictures (i6 mm) were\ntaken of all animals during the tests. Electro-oculography\nwas performed in three animals and frame projection\ncomparisons were made to estimate speed of movement\nin all animals. The following ocular motor functions,\nfor the most part, were routinely studied:\nI. Movements during spontaneous gaze (that\nis, the\npresence or absence of nystagmus, strabismus, skew"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1392
encoding: FLOAT32
metadata:
{"title": "Ocular motor dysfunction in total and hemicerebellectomized monkeys", "chroma:document": "deviation, conjugate gaze weakness, or deviation)\nDr James L. O'Leary died in May '975\nSupported in part by grants NS-o8o33, NS-o6563, NS-O4513 from\nthe National Institutes for Neurological Disease and Stroke, Bethesda,\nMaryland, and by grant EY-oooi6 from the National Eye Institute,\nBethesda, Maryland\nAddress\nfor reprints: Ronald M. Burde, MD, Department of\nOphthalmology, Washington University School of Medicine, 66o\nSouth Euclid Avenue, St Louis, Missouri 63110, USA\nz. Horizontal and vertical saccades\n3. Following movements\n4. Convergence function\n5. Horizontal and vertical optokinetic nystagmus\n6. Doll's head manoeuvre\n7. Cold water calorics (30\u00b0C).\nWarm water calorics (44\u00b0C) were performed when\nindicated. A special canaliculus extension earpiece of\nTeflon tubing (I mm internal diameter) was inserted\ninto the external auditory meatus of each animal and\nthreaded into the bony canal to ensure adequate stimulus\ndelivery. Then I 5 cms water was flushed into the external\near in approximately\nIS seconds.\nAnimals were divided arbitrarily into two groups:\nAcute-xamined within the first 8 weeks of surgery.\nCompensated-examined in the ninth week or later.\nResults\nAdequate data were available in io animals which\nunderwent total cerebellectomy and in two animals\nthat underwent hemicerebellectomy. The results\nare summarized in Tables I and II.\nIn animals that underwent total cerebellectomies\nand which were studied during the acute period the\nfollowing eye movement abnormalities were noted:\nI. Spontaneous gaze\nSpontaneous nystagmus was noted constantly in\ntwo\nof seven\nanimals. This was an upbeating\nnystagmus\n(fast phase up). An\nadditional four\nanimals had intermittent nystagmus, usually hori-\nzontal, but occasionally with an oblique component.\nGaze-paretic nystagmus (that is, nystagmus in\nconjugate lateral gaze with a small amplitude and\nhigh frequency) was present in four of six monkeys.\nThis was a horizontal movement in lateral gaze\n(fast phase right in right gaze and vice versa), and a"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1393
encoding: FLOAT32
metadata:
{"title": "Ocular motor dysfunction in total and hemicerebellectomized monkeys", "chroma:document": "vertical movement in vertical gaze, usually up-\nbeating when looking up and downbeating when\nlooking\ndown.\nGenerally\nthe\nnystagmus\nwas\nbilateral and symmetrical. In one animal (No. 13),\nthat underwent first a left cerebellectomy followed\nby a right cerebellectomy, the gaze-paretic nystag-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1394
encoding: FLOAT32
metadata:
{"title": "Hereditary pancreatitis in England and Wales", "chroma:document": "Journal ofMedical Genetics, 1978, 15, 189-201\nHereditary pancreatitis in England and Wales'\nJ. R. SIBERT\nFrom the Department ofChild Health, University Hospital of Wales, Cardiff\nSUMMARY\nInformation from 72 patients from 7 families in England and Wales confirms that\nhereditary pancreatitis is inherited as an autosomal dominant condition with limited penetrance. The\ndegree of penetrance is approximately 80%. These patients have had recurrent attacks of abdominal\npain starting from childhood or young adult life. The mean age of onset in the 7 families studied was\n13.6 years. There were two peaks, with maximum numbers at 5 years and 17 years. The second peak\nwas thought to represent genetically susceptible individuals having pain brought on by alcohol rather\nthan representing evidence of genetic heterogeneity. Five of the 7 families had members with both\nchildhood and adult ages of onset. Only 4 patients out of 72 had life-threatening disease and in the\nmajority of cases the attacks of pain were of nuisance value only. Hereditary pancreatitis was\nimplicated in only 1 patient's death and this was not definite. Patients appear to get better after a\nperiod of symptoms usually as they approach middle age, or after a severe attack. In older patients\nalcohol, emotional upsets, and fatty food appear to precipitate attacks. Pancreatic insufficiency\n(5.5%), diabetes mellitus (12.5%), pseudocysts (5.5%), and haemorrhagic pleural effusion\nare\nuncommon complications. Portal vein thrombosis occurred definitely in 2 patients and was suspected\nin 3 others. Carcinoma of the pancreas was not found in any of 72 patients studied in detail; however,\n2 members from a family not visited personally had chronic pancreatitis and malabsorption going on\nto carcinoma. They may have suffered from a different disease.\nGenetic linkage information was too slight for many definite conclusions. However, there was no\nsuggestion of linkage with any of the markers tested.\nHereditary pancreatitis was first described by Comfort"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1395
encoding: FLOAT32
metadata:
{"title": "Hereditary pancreatitis in England and Wales", "chroma:document": "and Steinberg (1952), from the Mayo Clinic. They\ndescribed a family with 4 definite and 2 suspected\ncases of chronic relapsing pancreatitis starting in child-\nhood or young adult life. The pattern of inheritance\nappeared to be an autosomal dominant one with\nincomplete\npenetrance.\nFour\nother\nfamilies\nwere\ndescribed in the ensuing years from the Mayo Clinic\n(Gross and Comfort, 1957; Gross, 1958; Gross et al.,\n1962). The findings in those families confirmed the\ndominant mode of inheritance of the condition and the\nearly age of onset of the attacks of pain. Gross et al.\n(1962) reported in addition that 4 of these 5 families\nhad aminoaciduria. Most of their work on this was\nconfined to one family (the K kindred) who appeared\nto have a lysine-cystine aminoaciduria.\n'This work forms part of an MD Thesis accepted by the University of\nCambridge.\nReceived for publication 7 July 1977\nThe first family described outside the Mayo Clinic\nwas reported by Cornet et al. in 1962 from Nantes in\nFrance.\nInformation on\nanother\nfamily from the\nUnited States was published soon after (Gerber, 1963)\nand\nsince then there have been over 35\nfamilies\nreported in the world literature. These families have\ncome from all over the world; however, apart from the\nIndian family of Choudhry et al. (1971) all have come\nfrom patients of European ancetry. There have been\ntwo relatively recent reviews of the condition from the\nUnited States by McElroy and Christiansen (1972)\nand Kattwinkel et al. (1973).\nThe only reports of hereditary pancreatitis from the\nUnited Kingdom have been by Nash (1971) and a\nlarge family from Newcastle (Sibert, 1975). A study\nwas made on these and other families in England and\nWales to investigate the natural history of the con-\ndition, the evidence for genetic heterogeneity, the\npattern of inheritance, and the urine amino acids. A\n189"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1396
encoding: FLOAT32
metadata:
{"title": "Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World", "chroma:document": "Bringing Gene Therapies for HIV Disease to Resource-Limited\nParts of the World\nJoseph M. McCune,* Emily H. Turner, Adam Jiang, and Brian P. Doehle\nHIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation, Seattle, Washington, USA.\nINTRODUCTION\nDESPITE THE FACT that 59% of people living with HIV\n(PLHIV) currently achieve viral suppression on anti-\nretroviral therapy (ART), recent gains in controlling the\nglobal HIV/AIDS epidemic may be threatened: key HIV\nincidence rates are declining only modestly, the sustain-\nability of programs to expand ART remains unclear, and\nthe \u2018\u2018youth bulge\u2019\u2019 in sub-Saharan Africa contributes to a\ngrowing at-risk population.1 Although much effort has\nbeen devoted to prevention interventions, these face major\ntechnical and/or implementation challenges.\nA complementary approach is a safe, effective, and\ndurable intervention that completely eliminates HIV in-\nfection (\u2018\u2018eradication\u2019\u2019) or that suppresses viremia in the\nabsence of ART (\u2018\u2018remission\u2019\u2019) (both of these states are\nreferred to as an \u2018\u2018HIV cure\u2019\u2019 herein). Although a daunting\ngoal, the scienti\ufb01c basis is clear: long-term remission if not\neradication has been observed in the \u2018\u2018Berlin patient\u2019\u20192 as\nwell as the \u2018\u2018London patient\u2019\u20193 following transplantation\nof bone marrow progenitor cells lacking the viral cor-\neceptor, CCR5; and durable remission occurs in tens of\nthousands of PLHIV (so-called \u2018\u2018Elite Controllers\u2019\u2019), some\nof whom (\u2018\u2018Exceptional Elite Controllers\u2019\u2019) may have\neliminated their infections through natural immunity.4,5\nOngoing work over the past decade suggests that HIV\ncure might be induced by some interventions, alone or in\ncombination, including provision of broadly neutralizing\nantibodies, generation of effective antiviral CD8+ T cell\nresponses, and knockout of the viral coreceptor, CCR5.6\nLittle is known, however, about the nature and vulner-\nabilities of the rebound-competent viral reservoir that\npersists despite ART and about the immunologic control"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1397
encoding: FLOAT32
metadata:
{"title": "Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World", "chroma:document": "of virus in the absence of ART; today\u2019s \u2018\u2018best bets,\u2019\u2019 in\nother words, must still be viewed as long shots.\nInitiated by the Bill & Melinda Gates Foundation in\n2019, the HIV Frontiers Program aims to move work on\nHIV cure toward interventions that will ultimately be\navailable to all, most especially those in resource-limited\nparts of the world where the prevalence of disease is high\n(Fig. 1). It starts with the premise that the journey will\nbe long (15\u201325 years) and that it will ultimately yield a\n\u2018\u2018single-shot cure,\u2019\u2019 that is, a product that is delivered\npercutaneously (in vivo) in a single encounter, safely, and\neffectively modifying selected cells in the body so that\nviral replication and spread are suppressed and reinfection\nblocked.\nThis aspirational goal is likely to be realized through a\nseries of progressive interventions that move from com-\nbination therapies provided over a longer duration of time\nto those in which cells are modi\ufb01ed outside of the body (ex\nvivo) before reinfusion.7 The work will build on curr-\nent knowledge to advance through a series of technical and\npractical hurdles while also gathering new knowledge to\nbest design a curative intervention for HIV and to deter-\nmine whether and how it might be used.\nTo get to the point of having a \u2018\u2018single-shot cure\u2019\u2019 for\nHIV in hand, two interlocking areas of focus are being\npursued:\nCurrent best bets\nTo minimize the expected time to impact, investments\nare being made in all of the necessary elements of a\n\u2018\u2018single-shot\u2019\u2019 HIV cure in parallel. As a critical enabler,\nthe Program is leveraging the considerable interest and\nresources in biotech/pharma companies that are now\ndeveloping ex vivo genetic and cell-based interventions;\nuniquely among ongoing efforts, it intends to shift the\nemphasis of such interventions to delivery in vivo, an\n*Correspondence: Dr. Joseph M. McCune, HIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation, 500 5th Avenue North, Seattle,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1398
encoding: FLOAT32
metadata:
{"title": "Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World", "chroma:document": "WA 98109-4636, USA. E-mail: mike.mccune@gatesfoundation.org\n\u00aa Joseph M. McCune et al., 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://\ncreativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\nHUMAN GENE THERAPY, VOLUME 32, NUMBERS 1 and 2\nDOI: 10.1089/hum.2020.252 j 21\n2021 by Mary Ann Liebert, Inc."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1399
encoding: FLOAT32
metadata:
{"title": "Changes in circulating forms of anti-Muullerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy", "chroma:document": "Changes in circulating forms of\nanti-Muu\u00a8llerian hormone and\nandrogens in women with and without\nPCOS: a systematic longitudinal study\nthroughout pregnancy\nM. Peigne\u00b4\n1,2,3, V. Simon1,3, P. Pigny\n4, N. E. H. Mimouni\n1,\nC. Martin5, D. Dewailly\n1,3, S. Catteau-Jonard1,3,\u2020, and\nP. Giacobini\n1,\u2020*\n1Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Inserm, CHU Lille, Lille Neuroscience and\nCognition, UMR-S 1172, Lille, France 2Department of Reproductive Medicine and Fertility Preservation, AP-HP\u2014Universite\u00b4 Sorbonne\nParis-Nord, Jean Verdier Hospital, Bondy, France 3Department of Medical Gynecology, CHU Lille, Jeanne de Flandre Hospital, Lille,\nFrance\n4Department of Biochemistry and Hormonology, CHU Lille, Centre de Biologie Pathologie, Lille, France\n5Department of\nBiostatistics, CHU Lille, Lille, France\n*Correspondence address. Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Inserm, CHU Lille,\nLille Neuroscience and Cognition, UMR-S 1172, Building Biserte, 1 Place de Verdun, 59045 Lille Cedex, France. E-mail: paolo.giacobini@inserm.fr\nhttps://orcid.org/0000-0002-3075-1441\nSubmitted on December 12, 2022; resubmitted on February 23, 2023; editorial decision on March 1, 2023\nSTUDY QUESTION: What are the changes in serum concentration of total and cleaved anti-Muu\u00a8llerian hormone (AMH) molecular\nforms and of androgens before and throughout pregnancy in women with and without polycystic ovary syndrome (PCOS) in a longitudinal\nfollow-up investigation?\nSUMMARY ANSWER: Serum levels of total and cleaved AMH are higher from preconception to the third trimester of pregnancy in\nwomen with PCOS as compared to controls, whereas testosterone and androstenedione levels are higher in women with PCOS than in\ncontrol women before pregnancy and during the second and third trimester of pregnancy.\nWHAT IS KNOWN ALREADY: Cross-sectional or partial longitudinal studies have shown higher AMH and androgen levels in pregnant"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1400
encoding: FLOAT32
metadata:
{"title": "Changes in circulating forms of anti-Muullerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy", "chroma:document": "women with PCOS as compared with non-PCOS women. To date, no complete longitudinal dynamic monitoring of the circulating forms\nof AMH and androgens from pre-conception to the third trimester of pregnancy have compared women with and without PCOS.\nSTUDY DESIGN, SIZE, DURATION: This systematic prospective quarterly longitudinal monocentric study was a comparative\nfollow-up of 30 women with PCOS and 29 controls before and during pregnancy from April 2019 to July 2022.\nPARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18\u201343 years with a pre-conception measurement of AMH\nwere included during the \ufb01rst trimester of a singleton pregnancy. The PCOS group was de\ufb01ned according to the Rotterdam diagnostic\ncriteria. The control group patients included in the study had normal ovarian reserves. Circulating total and cleaved AMH, and serum\nestradiol, LH, and androgen levels were measured during the \ufb01rst, second, and third trimester of pregnancy in all study participants.\nMAIN RESULTS AND THE ROLE OF CHANCE: Before pregnancy, patients with PCOS had higher levels of AMH than controls. The\ntotal and cleaved AMH forms were signi\ufb01cantly higher in women with PCOS than controls from pre-conception to the third trimester\nof pregnancy (all P < 0.001). Androgens (total testosterone and androstenedione) were higher in women with PCOS than controls from\nmid-pregnancy onwards.\nLIMITATIONS, REASONS FOR CAUTION: Our control population was a population of infertile women with no ovarian problems\nbut most of them had undergone ART treatments to achieve pregnancy.\n\u2020These authors contributed equally to this work.\nV\nC The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1401
encoding: FLOAT32
metadata:
{"title": "Changes in circulating forms of anti-Muullerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy", "chroma:document": "permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact\njournals.permissions@oup.com\nHuman Reproduction, Vol.38, No.5, pp. 938\u2013950, 2023\nAdvance Access Publication on March 15, 2023\nhttps://doi.org/10.1093/humrep/dead050\nORIGINAL ARTICLE Reproductive endocrinology"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1402
encoding: FLOAT32
metadata:
{"title": "Changes in circulating forms of anti-Muullerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout", "chroma:document": "Offspring physiology following the use\nof IVM, IVF and ICSI: a systematic\nreview and meta-analysis of animal\nstudies\nKiri H. Beilby\n1,*, Ezra Kneebone1, Tessa J. Roseboom2,\nIndah M. van Marrewijk3,4, Jeremy G. Thompson3,5,\nRobert J. Norman3, Rebecca L. Robker\n3, Ben Willem J. Mol\n1,6,\nand Rui Wang\n1\n1Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia 2Department of Obstetrics and Gynaecology,\nAcademic Medical Centre, Amsterdam, The Netherlands\n3The Robinson Research Institute, School of Biomedicine, University of\nAdelaide, Adelaide, Australia 4Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre, Rotterdam, The\nNetherlands 5ARC Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, Australia 6Aberdeen Centre for\nWomen\u2019s Health Research, University of Aberdeen, Aberdeen, UK\n*Correspondence address. Department of Obstetrics and Gynaecology, Monash University, Level 5, Monash Medical Centre, 246 Clayton\nRoad, Clayton, VIC 3168, Australia. E-mail: kiri.beilby@monash.edu\nhttps://orcid.org/0000-0002-1378-5586\nSubmitted on March 29, 2022; resubmitted on November 24, 2022; editorial decision on December 5, 2022\nTABLE OF CONTENTS\n................................................................................................................................\n\u2022 Introduction\n\u2022 Methods\nSearch strategy\nEligibility criteria\nExperimental ART protocols\nOutcomes\nStudy selection, data extraction and risk of bias assessment\nData synthesis\n\u2022 Results\nSearch results\nStudy characteristics\nRisk of bias\nBirthweight\nLength of gestation\nBlood pressure\nMetabolic outcomes\nBehaviour outcomes\nLifespan\n\u2022 Discussion\nSummary of key findings\nInterpretation\nV\nC The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1403
encoding: FLOAT32
metadata:
{"title": "Changes in circulating forms of anti-Muullerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout", "chroma:document": "permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact\njournals.permissions@oup.com\nHuman Reproduction Update, Vol.29, No.3, pp. 272\u2013290, 2023\nAdvance Access Publication on January 5, 2023\nhttps://doi.org/10.1093/humupd/dmac043"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1404
encoding: FLOAT32
metadata:
{"title": "Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations", "chroma:document": "Cyclic processes in the uterine tubes, endometrium,\nmyometrium, and cervix: pathways and perturbations\nSarah J. Holdsworth-Carson\n1,2,*, Ellen Menkhorst\n2, Jacqueline A. Maybin\n3, Anna King4, Jane E. Girling\n2,5\n1Julia Argyrou Endometriosis Centre, Epworth HealthCare, Melbourne, Australia\n2Department of Obstetrics and Gynaecology, University of Melbourne and Gynaecology Research Centre, Royal Women\u2019s Hospital, Melbourne, Australia\n3Institute for Regeneration and Repair, MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK\n4Department of Obstetrics and Gynaecology, NHS Lothian, Edinburgh, UK\n5Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand\n*Correspondence address. Julia Argyrou Endometriosis Centre, Epworth HealthCare, Ground Floor, 175-185 Hoddle St, Richmond 3121 VIC, Australia.\nE-mail: sarah.holdsworth-carson@epworth.org.au\nhttps://orcid.org/0000-0002-3533-0486\nAbstract\nThis review leads the 2023 Call for Papers in MHR: \u2018Cyclical function of the female reproductive tract\u2019 and will outline the complex and fas-\ncinating changes that take place in the reproductive tract during the menstrual cycle. We will also explore associated reproductive tract\nabnormalities that impact or are impacted by the menstrual cycle. Between menarche and menopause, women and people who menstru-\nate living in high-income countries can expect to experience \u0002450 menstrual cycles. The primary function of the menstrual cycle is to\nprepare the reproductive system for pregnancy in the event of fertilization. In the absence of pregnancy, ovarian hormone levels fall, trig-\ngering the end of the menstrual cycle and onset of menstruation. We have chosen to exclude the ovaries and focus on the other structures\nthat make up the reproductive tract: uterine tubes, endometrium, myometrium, and cervix, which also functionally change in response\nto \ufb02uctuations in ovarian hormone production across the menstrual cycle. This inaugural paper for the 2023 MHR special collection will"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1405
encoding: FLOAT32
metadata:
{"title": "Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations", "chroma:document": "discuss our current understanding of the normal physiological processes involved in uterine cyclicity (limited speci\ufb01cally to the uterine\ntubes, endometrium, myometrium, and cervix) in humans, and other mammals where relevant. We will emphasize where knowledge\ngaps exist and highlight the impact that reproductive tract and uterine cycle perturbations have on health and fertility.\nKeywords: menstrual cycle / endometrium / myometrium / cervix / uterine tube / fertility / fallopian tube / menstruation\nIntroduction\nThe menstrual cycle encompasses the series of changes in hor-\nmone production that result in alteration of the structure and\nfunction of the female reproductive tract, including the uterine\ntubes (oviduct or fallopian tube), uterus, and uterine cervix.\nWomen and others who menstruate in high-income countries\ncan expect to experience \u0002450 menstrual cycles in their lifetime\n(reviewed by Eaton et al. (1994) and Critchley et al. (2020a)). The\nfirst occurrence of menstruation is termed menarche and the av-\nerage age of menarche in high-income countries is 12.5 years\n(Morris et al., 2011; Colich et al., 2020; Martinez, 2020). At the other\nend of the reproductive lifespan, menopause is defined as the\npermanent cessation of menstruation resulting from the loss of\novarian follicular activity. Natural menopause is recognized to\nhave occurred after 12 consecutive months of amenorrhoea, for\nwhich there is no other obvious pathological or physiological\ncause. The average age of menopause in high-income countries\nis 50.5 years, but this is affected by demographic, reproductive,\ngenetic, and environmental factors (Gold, 2011).\nThe primary function of the menstrual cycle is to prepare the re-\nproductive system for pregnancy should fertilization occur. The first\nday of menstrual bleeding is designated as Day 1 of the menstrual\ncycle and the typical length of a cycle is 24\u201338days (Munro et al.,\n2018). During the first part of the menstrual cycle, the follicular or"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1406
encoding: FLOAT32
metadata:
{"title": "Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations", "chroma:document": "menstrual/proliferative phase, oestradiol (E2) is the dominant ovar-\nian hormone (Fig. 1). Following ovulation, the corpus luteum\nsecretes high levels of progesterone (P4) during the luteal/secretory\nphase to decidualize and prepare the endometrium for possible im-\nplantation (Fig. 1). The corpus luteum also secretes relaxin in the\nlatter half of the secretory phase; its levels are otherwise low or\nundetectable in humans during the other phases of the cycle\n(Marshall et al., 2017). In the absence of pregnancy, the ovarian hor-\nmone levels fall, with the fall in P4 triggering the end of the men-\nstrual cycle and onset of menstruation (Fig. 1). The changes in\nuterine tubal, endometrial, myometrial, and cervical structure and\nfunction in response to fluctuations in ovarian hormone production\nare the subject of this review. Here, we cover the complex, highly\ncoordinated processes of vascular function, inflammation, and tis-\nsue remodelling that occur throughout the menstrual cycle in the\nreproductive tract. Current understanding of the physiology of the\nmenstrual cycle will be reviewed before examination of the patholo-\ngies caused, linked, or exacerbated by cyclical pathways. We hope\nthis review will not only illustrate the current knowledge of the\nfunctional and mechanistic pathways related to the reproductive\ntract and menstrual cycle but also highlight the historical lack of re-\nsearch focus in this area, particularly with respect to the uterine\ntube, myometrium, and cervix. Our review is the first paper in the\nReceived: December 19, 2022. Revised: March 01, 2023. Editorial decision: March 31, 2023.\nV\nC The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which\npermits unrestricted reuse, distribution, and reproduction 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: 1407
encoding: FLOAT32
metadata:
{"title": "Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations", "chroma:document": "Molecular Human Reproduction, 2023, 29(5), gaad012\nhttps://doi.org/10.1093/molehr/gaad012\nReview"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1408
encoding: FLOAT32
metadata:
{"title": "SKF96365 modulates activity of CatSper channels in human sperm", "chroma:document": "SKF96365 modulates activity of CatSper channels in\nhuman sperm\nElis Torrezan-Nitao1, Sean G. Brown\n2, Linda Lefievre3, Jennifer Morris1, Joao Correia\n1,4, Claire V. Harper\n5, and\nStephen Publicover\n1,*\n1School of Biosciences, University of Birmingham, Birmingham, UK\n2School of Applied Sciences, Division of Health Sciences, Abertay University, Dundee, UK\n3Institute of Clinical Sciences, School of Biomedical Sciences, University of Birmingham, Birmingham, UK\n4Institute of Metabolism and Systems Research, School of Biomedical Sciences, University of Birmingham, Birmingham, UK\n5Department of Biology, Faculty of Arts and Sciences, Edge Hill University, Ormskirk, Lancashire, UK\n*Correspondence address. School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK. E-mail: s.j.publicover@bham.ac.uk\nhttps://orcid.org/0000-0002-2911-5288\nAbstract\nExposure of human sperm to progesterone (P4) activates cation channel of sperm (CatSper) channels, inducing an intracellular Ca2\u00fe\nconcentration ([Ca2\u00fe]i) transient followed by repetitive [Ca2\u00fe]i activity (oscillations), which are believed to be functionally important.\nWe investigated the potential signi\ufb01cance of store-operated Ca2\u00fe-entry in these oscillations using the inhibitor SKF96365 (30 mM;\nSKF). Following pre-treatment of human sperm with 3 mM P4, exposure to SKF doubled the proportion of oscillating cells (P \u00bc 0.00004).\nIn non-pre-treated cells, SKF had an effect similar to P4, inducing a [Ca2\u00fe]i transient in >80% of cells which was followed by oscilla-\ntions in \u000250% of cells. The CatSper blocker RU1968 (11 mM) inhibited the SKF-induced [Ca2\u00fe]i increase and reversibly arrested [Ca2\u00fe]i\noscillations. Using whole-cell patch clamp, we observed that SKF enhanced CatSper currents by 100% within 30 s, but amplitude then\ndecayed to levels below control over the next minute. When cells were stimulated with P4, CatSper currents were stably increased"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1409
encoding: FLOAT32
metadata:
{"title": "SKF96365 modulates activity of CatSper channels in human sperm", "chroma:document": "(by 200%). Application of SKF then returned current amplitude to control level or less. When sperm were prepared in medium lacking\nbovine serum albumin (BSA), both P4 and SKF induced a [Ca2\u00fe]i transient in >95% of cells but the ability of SKF to induce oscillations\nwas greatly reduced (P \u00bc 0.0009). We conclude that SKF, similar to a range of small organic molecules, activates CatSper channels, but\nthat a secondary blocking action also occurs, which was detected only during patch-clamp recording. The failure of SKF to induce\noscillations when cells were prepared without BSA emphasizes that the drug does not fully mimic the actions of P4.\nKeywords: human sperm / SKF96365 / CatSper / progesterone / calcium / calcium oscillations / patch clamp / cation channel of\nsperm\nIntroduction\nIntracellular Ca2\u00fe concentration ([Ca2\u00fe]i) signalling is crucial to\nsperm function, being a key regulator of motility, acrosome reac-\ntion, and capacitation (Darszon et al., 2005; Publicover et al., 2008;\nPrajapati et al., 2022). A number of stimuli, including zona pellu-\ncida (ZP), are believed to regulate human sperm function by this\npathway, the best characterized being the steroid progesterone\n(P4), which is secreted by the cells of the cumulus and is present\nthroughout the female tract (Correia et al., 2007). P4 acts on hu-\nman sperm by activation of the sperm-specific Ca2\u00fe-permeable\nchannel CatSper (Lishko et al., 2011; Strunker et al., 2011), which,\nin human sperm and those of many other species, is the principal\nmechanism of Ca2\u00fe mobilization (Lishko et al., 2012; Lishko and\nMannowetz, 2018).\nIn addition to CatSper, Ca2\u00fe stores and capacitative (store-\noperated) Ca2\u00fe entry (CCE) are implicated in sperm [Ca2\u00fe]i signal-\nling (Costello et al., 2009; Correia et al., 2015). CCE may be\ntriggered by CatSper-mediated elevation of [Ca2\u00fe]i, serving to am-\nplify, propagate and/or prolong the [Ca2\u00fe]i signal (Alasmari et al.,\n2013; Correia et al., 2015). No specific pharmacological agents are"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1410
encoding: FLOAT32
metadata:
{"title": "SKF96365 modulates activity of CatSper channels in human sperm", "chroma:document": "available for blockade of CCE, but 10\u201330 mM SKF96365 (SKF) is a\nknown and well-characterized antagonist of CCE both in cell lines\nand in a range of acutely cultured cell types (Labelle et al., 2007;\nNg et al., 2008, 2010; Li et al., 2010; Sabourin et al., 2016). SKF has\nalso been shown to inhibit calcium-release activated Ca2\u00fe (CRAC)\ncurrent (a form of CCE; Parekh and Putney, 2005) in cells where\nCRAC currents occur naturally and also in cells transfected with\nOrai, a pore forming channel which is involved in CRAC and other\nCCE channels (Prakriya and Lewis, 2002; Yeromin et al., 2006;\nVarnai et al., 2009).\nSKF has been used as a tool to investigate the participation of\nCCE in sperm functions. Treatment with SKF inhibited acrosome\nreaction in sea urchin sperm (Hirohashi and Vacquier, 2003) and\nsuppressed the increase in [Ca2\u00fe]i induced by mitochondrial\ninhibitors (Ardon et al., 2009). In mouse sperm, SKF inhibited\nCa2\u00fe influx and acrosome reaction induced by maitotoxin\n(Trevino et al., 2006) and suppressed motility (Ru et al., 2015). In\nhuman sperm, SKF has been reported to suppress motility\n(Castellano et al., 2003) to inhibit acrosomal swelling (believed to\nbe a key stage in acrosome reaction) induced by P4 and by thap-\nsigargin, which mobilizes stored Ca2\u00fe; Sosa et al., 2016), and to\nReceived: December 07, 2022. Revised: March 17, 2023. Editorial decision: April 24, 2023.\nV\nC The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which\npermits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.\nMolecular Human Reproduction, 2023, 29(6), gaad015\nhttps://doi.org/10.1093/molehr/gaad015\nAdvance Access Publication Date: April 27, 2023\nOriginal Research"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1411
encoding: FLOAT32
metadata:
{"title": "Molecular taxonomy of nociceptors and pruriceptors", "chroma:document": "Biennial Review of Pain\nMolecular taxonomy of nociceptors\nand pruriceptors\nJussi Kupari, Patrik Ernfors*\n1. Introduction\nThe ability to feel the warmth of the sun or the coolness of a\nbreeze on a summer\u2019s day; a pleasant caress of skin; to explore\nthe texture, size, and shape of an object; and to feel pain as a\nmechanism to protect us from what is dangerous around us has\nfascinated mankind for centuries. Perhaps this fascination is\nrooted in the fact that the somatic senses of temperature, pain,\ntouch, itch, and proprioception endow us with the ability to\ncontinuously stay in contact with the world within and around us.\nAttempting to explain how we react to heat, the 17th century\nphilosopher Ren \u00b4e Descartes depicted a thread connecting the\nskin with the brain and particles of fire pulling on the thread.20 In\nthe 1880s, distinct sensory spots on the skin were recognized\nand shown to respond to specific stimuli, such as touch, heat, or\ncold. This finding was taken as evidence for different sensations\nrelying on the existence of distinct nerves tuned to specific types\nof stimuli.83,94 In the beginning of the 20th century, the discovery\nof different nerve fiber types with distinct conduction velocities,\nactivation thresholds, and refractory periods made it possible to\nlink specific fiber types to unique qualities of sensation, such as\nproprioception and different kinds of touch. Unlike innocuous\ntouch and pressure, which are communicated through nerve\nfibers responding only to mechanical stimuli, noxious stimuli were\nfound to activate a class of polymodal nociceptive nerve fibers\nresponding to several kinds of unpleasant stimuli, including high-\nthreshold mechanical force and intense heat.7,12 This work led to\nthe general idea that the capacity to discriminate perceptual\nqualities arises from unique functions of a variety of sensory\nneurons involved in somatic sensation. This is possible because\ndifferent neuron types are tuned to respond and transduce\ncertain, but not all, kinds of stimuli, such as warm and cool"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1412
encoding: FLOAT32
metadata:
{"title": "Molecular taxonomy of nociceptors and pruriceptors", "chroma:document": "temperatures,\nnoxious\nheat,\nnoxious\ncold,\nlight\npunctate\nsensation, painful pressure, sharp objects, hair pull, chemical\nirritants, inflammatory substances, chemical and mechanical\nitch, and various kinds of touch and vibration.29,38\nApart from providing sensory awareness about our body and\nits surroundings, the somatosensory system is also essential for\nother functions we perform effortlessly and without much\nthought. For example, a continuous flow of information in a\nsensory\u2013motor feedback loop involving several dozen muscles is\nnecessary to coordinate movements when taking a sip from a\nglass of water or for the seemingly simple task of walking.\nSomatosensory neurons are also organized in discreet pathways\nwith autonomic sympathetic and parasympathetic motor neu-\nrons driving reflexes involved in physiological homeostasis, such\nas thermoregulation through reflex control of sweat glands and\nselective vasoconstrictor systems in muscle and skin active when\nstanding up and during hypothermia, respectively.16,49,74 Fur-\nthermore, pleasant and painful sensations involve not only\ndiscriminative perception and coordination of efferent reflex\nfunctions but also emotional and motivational components\nimportant for behavior. For example, social touch such as\nhugging and caressing induce sensations of pleasantness to\nfacilitate emotional bonding, affiliative behavior, and well-be-\ning,82,88 while noxious stimuli not only convey sensory discrim-\ninative and protective reflexes but also include an affective-\nmotivational dimension of unpleasantness contributing to long-\nterm behavior avoiding harm.112,125\nThe existence of molecularly unique neuron types coding for\neach quality and dimension of somatosensation is unlikely.\nInstead, summation of activity and inactivity from different types of\nnerve fibers is likely to contribute to the sensory qualities and\ndimensions involved. Several recent studies support this conjec-\nture, eg. the discovery of warmth sensation relying on the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1413
encoding: FLOAT32
metadata:
{"title": "Molecular taxonomy of nociceptors and pruriceptors", "chroma:document": "simultaneous activation of warmth-sensing and inhibition of cold-\nsensing nerves97; the requirement of different sensory neurons\nfor protective reflexes and affective coping behavior elicited by the\nsame stimuli45; the suppression of noxious cold (210 to 10\u02daC) by\nCalca1 neurons18,81; the modulation of touch-evoked itch by\nMerkel cells and Slc17a8-lineage (low-threshold mechanorecep-\ntor [LTMR]) sensory neurons32,33,108; and alleviation of Npy2r1\nneuron-dependent acute pain behavior by the simultaneous\nactivity of the A-LTMR touch neurons.3 With a thorough\nmolecular categorization of sensory neuron types, experiments\ncan be designed with even greater precision, opening possibilities\nfor gaining new, deeper insights into the cellular basis for\nnociception and pruriception.\n2. Categorizing sensory neurons\nSensory neurons have historically been classified based on\nphysiological properties, morphology, target innervation, spinal\ntermination, developmental hierarchy, and functional and neuro-\nchemical properties (reviewed by Emery and Ernfors, 202029).\nSponsorships or competing interests that may be relevant to content are disclosed\nat the end of this article.\nDivision of Molecular Neurobiology, Department of Medical Biochemistry and\nBiophysics, Karolinska Institutet, Stockholm, Sweden\n*Corresponding author. Address: C2 Medicinsk biokemi och biofysik, C2 Molekyl \u00a8ar\nneurobiologi Ernfors, Solnav \u00a8agen 9, 6C, 17177 Stockholm, Sweden. Tel.: 146 8-\n524 876 59. E-mail address: patrik.ernfors@ki.se (P. Ernfors).\nPAIN 164 (2023) 1245\u20131257\nCopyright \u00a9 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf\nof the International Association for the Study of Pain. This is an open access article\ndistributed under the Creative Commons Attribution License 4.0 (CCBY), which\npermits unrestricted use, distribution, and reproduction in any medium, provided the\noriginal work is properly cited.\nhttp://dx.doi.org/10.1097/j.pain.0000000000002831\nJune 2023\u00b7Volume 164\u00b7Number 6\nwww.painjournalonline.com\n1245"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1414
encoding: FLOAT32
metadata:
{"title": "An epidemic of picornavirus and adenovirus conjectivitis", "chroma:document": "Brit. J. Ophthal. (I 975) 59, 439\nAn epidemic of picornavirus and adenovirus conjunctivitis\nU. C. CHATURVEDI, ASHA MATHUR, U. K. SINGH, A. K. KAPOOR,\nR. M. L. MEHROTRA, AND R. C. SAXENA\nFrom the Upgraded Department of Pathology and Bacteriology, K.G. Medical College, Lucknow, India\nA pandemic of acute haemorrhagic conjunctivitis\noccurred all over south-east Asia and Japan during\n1970 and\n1971\n(Kono, Sasagawa,\nIshii, Sugiura,\nOchi,\nMatsumiya,\nUchida, Kameyama,\nKaneko,\nand Sakurai, 1972). A similar epidemic occurred in\nI969\nin Ghana\n(Chatterjee,\nQuarcoopome,\nand\nApenteng, I97oa, b) and Nigeria (Parrott,\nI971).\nIn the Indian subcontinent the epidemic of con-\njunctivitis was first reported in Bombay during April\n1971, and later spread almost all over India. Cases\nof\nconjunctivitis\nstarted\nincreasing\nat\nLucknow\nduring the last week of May I97i, reaching a peak\nin June, and declining by July. Picorna-like viruses\nhave been isolated from cases in Singapore (Lim\nand Yin-Murphy, 1971; Yin-Murphy, 1972) and in\nJapan (Kono and others, I972). The epidemic at\nLucknow was peculiar in that adenoviruses as well\nas picornaviruses appear to have been present in\nthese cases.\nMaterial and methods\nThe study was carried out by the ophthalmologist (RCS)\non 253 typical cases of conjunctivitis which presented at\nGandhi Memorial and associated hospitals for treatment.\nOut of 253 patients 84-5 per cent were aged between\nI I\nand 40 years. The youngest was 3 years old and the oldest\n65 years. The illness started unilaterally, and most of the\npopulation at Lucknow was affected. There were multiple\ncases in a family and the infection could be transmitted\neven by casual conversation. The incubation period was less\nthan 24 hours in most cases. The chief complaints were a\ngritty sensation in the eyes, watering, and photophobia.\nA few patients had upper respiratory symptoms. Ocular\nexamination revealed redness, oedema of the conjunctiva\nand lids, subconjunctival haemorrhage in a number of\ncases, and enlarged preauricular lymph nodes. The cornea"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1415
encoding: FLOAT32
metadata:
{"title": "An epidemic of picornavirus and adenovirus conjectivitis", "chroma:document": "remained unaffected. The detailed clinical findings have\nbeen reported by Saxena, Bhatia, and Chaturvedi (1972).\nLABORATORY STUDIES\nThe laboratory investigations included total and differ-\nential leucocyte counts and conjunctival swab cultures\non blood agar and Robertson's cooked meat medium.\nAddress for reprints: Dr U. C. Chaturvedi, Upgraded Department of\nPathology and Bacteriology,\nK.G.\nMedical\nCollege,\nLucknow-\n226003, India\nBacteria were identified by their morphology, cultural\ncharacters,\nand\nbiochemical\nreactions.\nSmears\nwere\nprepared from conjunctival scrapings of 6i patients and\nstained with Giemsa stain to study the pattern of cellular\ninfiltration and to determine whether inclusion bodies\nsuggestive of viral infection would be found.\nVIROLOGICAL INVESTIGATIONS\nConjunctival swabs and scrapings\nwere\ncollected\nfor\nvirological study within 48 hours of the onset of illness.\nPaired sera were collected from I5 patients for study of\nantibody titres.\nVIRUS ISOLATION\nThis was done on primary rhesus monkey kidney tissue\nculture. Each sample was inoculated into a group of four\ntissue culture tubes. These were incubated stationary at\n370C and were examined daily for 15 days. Tubes showing\ncytopathic effects were subcultured.\nADENOVIRUS SEROLOGY\nHaemagglutination test\nThe cytopathic agents were tested for haemagglutinin\nusing albino rat and rhesus monkey erythrocytes. It was\nfound that only rat erythrocytes were agglutinated by the\nisolates; therefore for further experiments only erythro-\ncytes from albino rats were used, taking the precautions\ndescribed by Rosen (I960). Hyperimmune antisera were\nraised against two of the isolates in rabbits by the tech-\nnique of Rosen (I960). After treating the hyperimmune\nsera with 25 per cent kaolin and absorption with rat\nerythrocytes, a haemagglutination inhibition (HI)\ntest\nwas performed on all the isolates. The HI\ntests were\nrepeated in the presence of heterologous antisera (Rosen,\n1960). With eight of the selected\nisolates chessboard"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1416
encoding: FLOAT32
metadata:
{"title": "An epidemic of picornavirus and adenovirus conjectivitis", "chroma:document": "titrations were done using the hyperimmune sera described\nabove. Paired sera collected during the acute phase and in\nconvalescence were tested for HI antibodies against one\nof the isolates.\nELECTRON MICROSCOPY\nOne ofthe agents was studied under the electron microscope\nin the monkey kidney tissue culture fluid and after passage\nin HeLa cells at Birmingham.\nIDENTIFICATION\nThis agent was finally identified at the Virus Reference\nLaboratory, London, by a neutralization test."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1417
encoding: FLOAT32
metadata:
{"title": "Transciptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease", "chroma:document": "Transcriptional Profiling of Human Liver Identifies Sex-\nBiased Genes Associated with Polygenic Dyslipidemia\nand Coronary Artery Disease\nYijing Zhang1, Kathrin Klein2, Aarathi Sugathan1, Najlla Nassery1, Alan Dombkowski3, Ulrich M. Zanger2,\nDavid J. Waxman1*\n1 Division of Cell and Molecular Biology, Department of Biology, Boston University, Boston, Massachusetts, United States of America, 2 Dr. Margarete Fischer-Bosch\nInstitute of Clinical Pharmacology, Stuttgart, Germany, 3 Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Wayne State University, Detroit,\nMichigan, United States of America\nAbstract\nSex-differences in human liver gene expression were characterized on a genome-wide scale using a large liver sample\ncollection, allowing for detection of small expression differences with high statistical power. 1,249 sex-biased genes were\nidentified, 70% showing higher expression in females. Chromosomal bias was apparent, with female-biased genes enriched\non chrX and male-biased genes enriched on chrY and chr19, where 11 male-biased zinc-finger KRAB-repressor domain\ngenes are distributed in six clusters. Top biological functions and diseases significantly enriched in sex-biased genes include\ntranscription, chromatin organization and modification, sexual reproduction, lipid metabolism and cardiovascular disease.\nNotably, sex-biased genes are enriched at loci associated with polygenic dyslipidemia and coronary artery disease in\ngenome-wide association studies. Moreover, of the 8 sex-biased genes at these loci, 4 have been directly linked to\nmonogenic disorders of lipid metabolism and show an expression profile in females (elevated expression of ABCA1, APOA5\nand LDLR; reduced expression of LIPC) that is consistent with the lower female risk of coronary artery disease. Female-biased\nexpression was also observed for CYP7A1, which is activated by drugs used to treat hypercholesterolemia. Several sex-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1418
encoding: FLOAT32
metadata:
{"title": "Transciptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease", "chroma:document": "biased drug-metabolizing enzyme genes were identified, including members of the CYP, UGT, GPX and ALDH families. Half of\n879 mouse orthologs, including many genes of lipid metabolism and homeostasis, show growth hormone-regulated sex-\nbiased expression in mouse liver, suggesting growth hormone might play a similar regulatory role in human liver. Finally,\nthe evolutionary rate of protein coding regions for human-mouse orthologs, revealed by dN/dS ratio, is significantly higher\nfor genes showing the same sex-bias in both species than for non-sex-biased genes. These findings establish that human\nhepatic sex differences are widespread and affect diverse cell metabolic processes, and may help explain sex differences in\nlipid profiles associated with sex differential risk of coronary artery disease.\nCitation: Zhang Y, Klein K, Sugathan A, Nassery N, Dombkowski A, et al. (2011) Transcriptional Profiling of Human Liver Identifies Sex-Biased Genes Associated\nwith Polygenic Dyslipidemia and Coronary Artery Disease. PLoS ONE 6(8): e23506. doi:10.1371/journal.pone.0023506\nEditor: Xin Wei Wang, National Cancer Institute, United States of America\nReceived December 31, 2010; Accepted July 19, 2011; Published August 12, 2011\nCopyright: \u0002 2011 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits\nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nFunding: This research was supported in part by National Institutes of Health grant DK33765 (to D.J.W.), the German Federal Ministry of Education and Research\ngrant \u2018\u2018Virtual Liver\u2019\u2019 0315755 and the Robert Bosch Foundation, Stuttgart, Germany (to U.M.Z.). These funding agencies had no role in study design, data\ncollection and analysis, decision to publish, or preparation of the manuscript.\nCompeting Interests: The authors have declared that no competing interests exist.\n* E-mail: djw@bu.edu\nIntroduction"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1419
encoding: FLOAT32
metadata:
{"title": "Transciptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease", "chroma:document": "Mammalian sex determination is initiated by the SRY gene,\nwhich activates a developmental pathway leading to testis\nformation and establishes life-long sex differences in the patterns\nof gonadal hormone secretion [1]. Gonadal hormones, in turn,\nexert permanent differentiating effects (\u2018organizational\u2019 actions) as\nwell as short-term stimulatory effects that lead to sex differences in\ngene expression in multiple tissues [2]. Sex differences are also\ninduced by non-gonadal signals and factors, including direct sex-\nbiased effects of individual X and Y-chromosome genes [3].\nEpigenetic modifications also play an important role in the\ndevelopment and maintenance of sexual dimorphism [4] by\nprocesses such as genetic imprinting [5,6] and X-chromosome\ninactivation [7,8,9]. Sex differences characterize histone acetyla-\ntion and histone methylation [10] and the expression of certain\nhistone demethylases [11,12]. Sexual differentiation is thus\nachieved through a complex interplay of multiple mechanisms\n[13].\nGlobal gene expression studies in mouse and rat liver have\nidentified .1,000 sex-dependent transcripts, which collectively\nhave a major impact on hepatic physiology, inflammatory\nresponses, diseased states, and the metabolism of steroids, drugs\nand environmental chemicals [14,15,16]. However, very little is\nknown about the sex-dependence of gene expression in human\nliver. Small but pharmacologically significant sex differences in the\nexpression of certain human hepatic drug-metabolizing CYP\nenzymes have been reported, most notably for CYP3A4 [17,18],\nhowever, only limited efforts have been made to identify sex\ndifferences in human liver on a larger scale [19]. Such studies have\nthe potential to elucidate clinically important sex differences in\nhuman hepatic physiology and pathophysiology, including sex\ndifferences in circulating lipid profiles, which are more favorable in\nwomen [20,21] and are associated with their lower risk of\nPLoS ONE | www.plosone.org\n1\nAugust 2011 | Volume 6 | Issue 8 | e23506"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1420
encoding: FLOAT32
metadata:
{"title": "Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques", "chroma:document": "886 \nVOLUME 20 | NUMBER 6 | JUNE 2017   nature neurOSCIenCe\nHumans differ from other primates in a number of aspects, most \nstrikingly with respect to their cognitive abilities. The human brain \nis a highly heterogeneous organ comprising many anatomically  \nand functionally distinct structures. These include the neocortex,  \na 2\u20135-mm thick structure covering brain hemispheres. Given that it is \nthe most recently evolved part of the brain, present only in mammals1, \nthe neocortex might plausibly harbor those changes responsible for \nuniquely human cognition. Specifically, cognitive functions unique to \nhumans or particularly pronounced in humans have been mapped to \nspecific neocortical areas, including specific areas of prefrontal cortex \n(PFC), using functional imaging experiments or cases of localized \nbrain damage2,3.\nIn search of mechanisms underlying human cognitive abilities,  \na number of studies have investigated differences in neocortex  \ncomposition between humans and nonhuman primates at different \nlevels of molecular organization, including gene expression, iden-\ntifying a number of human-specific gene expression features4\u20136. \nThese studies, performed on bulk tissue samples representing one  \nor more specific neocortical regions, were insufficient to yield a  \ncomprehensive picture of the molecular mechanisms underlying \nhuman cognition.\nThe neocortex itself has a complex laminar architecture, tradition-\nally divided into six layers based on visual examination of its histo-\nlogical organization1. Neocortical layers differ from each other in \nterms of both cell type composition and the direction of neuronal \nconnections7. Several studies have assessed gene expression in specific \ncortical layers. More than 5,000 genes were shown to have differential \nexpression across layers in the mouse neocortex based on cortical \nlayer samples dissected using laser capture microdissection (LCM) \nand measured using microarrays8,9 or high-throughput sequenc-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1421
encoding: FLOAT32
metadata:
{"title": "Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques", "chroma:document": "ing8. Similarly, 4,923 genes showed significant expression differences \namong cortical layers 2\u20135 when dissected using LCM from ten corti-\ncal regions of the macaque brain and measured using microarrays, \nwith most of the differences shared among regions10.\nIn addition to transcriptome-wide studies, expression differences \namong cortical layers in the mouse11 and human12 brains have pre-\nviously been assessed using in situ hybridizations, revealing several \nhundred mouse and 76 human genes showing visibly differential \nexpression among layers. Only one study so far, based on abundance \nquantification of 39 proteins in four different brain regions (cingu-\nlate, primary motor, somatosensory and primary visual cortices) of \neight humans and three chimpanzees, examined recent evolutionary \nchanges in gene expression across cortical layers13. That study did not \nquantitatively estimate the protein abundance differences between \nspecies in each layer, however. Thus, at present, we still lack system-\natic analysis of layer-related expression in the human brain, as well \nas identification of layer-related expression changes unique to the \nhuman brain.\nTo address this, we adopted an experimental procedure allowing \ncomprehensive profiling of transcripts present in different strata  \nof the cortical samples and applied this to assess gene expression  \nin a specific area of human, chimpanzee and macaque PFC across  \nall histologically defined cortical layers and the underlying  \nwhite matter.\n1CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, SIBS, CAS, Shanghai, China. 2Big Data Decision Institute, \nJinan University, Guangzhou, China. 3Skolkovo Institute of Science and Technology, Skolkovo, Russia. 4University of Chinese Academy of Sciences, Beijing, China. \n5Department of Neuroscience, National Research Center, Kurchatov Institute, Moscow, Russia. 6School of Life Science and Technology, ShanghaiTech University,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1422
encoding: FLOAT32
metadata:
{"title": "Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques", "chroma:document": "Shanghai, China. 7Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. 8Immanuel Kant Baltic Federal University, Kaliningrad, Russia. 9Comparative \nBiology group, PICB, SIBS, CAS, Shanghai, China. 10These authors contributed equally to this work. Correspondence should be addressed to P.K. (khaitovich@eva.mpg.de).\nReceived 27 June 2016; accepted 17 March 2017; published online 17 April 2017; doi:10.1038/nn.4548\nComprehensive transcriptome analysis of neocortical \nlayers in humans, chimpanzees and macaques\nZhisong He1,10  , Dingding Han1,2,10, Olga Efimova3, Patricia Guijarro1, Qianhui Yu1,4, Anna Oleksiak1,  \nShasha Jiang1, Konstantin Anokhin5, Boris Velichkovsky6, Stefan Gr\u00fcnewald1 & Philipp Khaitovich3,6\u20139\nWhile human cognitive abilities are clearly unique, underlying changes in brain organization and function remain unresolved. \nHere we characterized the transcriptome of the cortical layers and adjacent white matter in the prefrontal cortexes of humans, \nchimpanzees and rhesus macaques using unsupervised sectioning followed by RNA sequencing. More than 20% of detected \ngenes were expressed predominantly in one layer, yielding 2,320 human layer markers. While the bulk of the layer markers were \nconserved among species, 376 switched their expression to another layer in humans. By contrast, only 133 of such changes \nwere detected in the chimpanzee brain, suggesting acceleration of cortical reorganization on the human evolutionary lineage. \nImmunohistochemistry experiments further showed that human-specific expression changes were not limited to neurons but \naffected a broad spectrum of cortical cell types. Thus, despite apparent histological conservation, human neocortical organization \nhas undergone substantial changes affecting more than 5% of its transcriptome.\nr e S Ou rC e\n\u00a9 2017 Nature America, Inc., part of Springer Nature. All rights reserved."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1423
encoding: FLOAT32
metadata:
{"title": "Assembly of novel microbial genomes from gut metagenomes of rhesus macaque", "chroma:document": "RESEARCH PAPER\nAssembly of novel microbial genomes from gut metagenomes of rhesus \nmacaque (Macaca mulatta)\nShengzhi Yanga\u2020, Zhenxin Fana,b\u2020, Jiawei Lia, Xinqi Wanga, Yue Lana, Bisong Yuea,b, Miao Hec, Anyun Zhanga,d, \nand Jing Lia\naKey Laboratory of Bioresources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, Sichuan, \nChina; bSichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, \nSichuan, China; cInstitute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China; dAnimal Disease Prevention \nand Food Safety Key Laboratory of Sichuan Province, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of \nLife Sciences, Sichuan University, Chengdu, Sichuan, China\nABSTRACT\nRhesus macaque (RM, Macaca mulatta), as an important model animal, commonly suffers from \nchronic diarrheal disease, challenging the breeding of RMs. Gut microbiomes play key roles in \nmaintaining intestinal health of RMs. However, it is still unclear about more features of gut \nmicrobiome as responsible for intestinal health of RMs. In this study, we performed de novo \nassembly of metagenome-assembled genomes (MAGs) based on fecal metagenomes from chronic \ndiarrheal RMs and asymptomatic individuals. In total of 731 non-redundant MAGs with at least 80% \ncompleteness were reconstructed in this study. More than 97% MAGs were novel genomes \ncompared with more than 250,000 reference genomes. MAGs of Campylobacter and \nHelicobacteraceae from RM guts mainly carried flagella-associated virulence genes and chemo-\ntaxis-associated virulence genes, which might mediate motility and adhesion of bacteria. \nComparing to MAGs of Campylobacter from humans, distributions and functions of these MAGs \nof Campylobacter from RMs exhibited significant differences. Most members of Bacteroidota, \nSpirochaetota, Helicobacteraceae, Lactobacillaceae and Anaerovibrio significantly decreased in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1424
encoding: FLOAT32
metadata:
{"title": "Assembly of novel microbial genomes from gut metagenomes of rhesus macaque", "chroma:document": "guts of chronic diarrhea RMs. More than 92% MAGs in this study were not contained in 2,985 \nMAGs previously reported from other 22 non-human primates (NHPs), expanding the microbial \ndiversity in guts of NHPs. The distributions and functions of gut microbiome were prominently \ninfluenced by host phylogeny of NHPs. Our results could help to more clearly understand about the \ndiversity and function of RMs gut microbiome.\nARTICLE HISTORY \nReceived 17 August 2022  \nRevised 28 November 2022  \nAccepted 3 March 2023 \nKEYWORDS \nMacaca mulatta; \nMetagenomic binning; MAG; \nnon-human primate; gut \nmicrobiome; Campylobacter\nIntroduction\nDue to many populations and the similarity of \ngenetic evolution to human, rhesus macaque \n(RM, Macaca mulatta) generally serves as an \nimportant model animal to reveal physiology of \nhuman, research clinical disease and develop new \ndrugs.1\u20133 Therefore, RMs with huge needs are \nwidely raised in captivity as model animal. \nHowever, many captive RMs usually suffer from \nchronic diarrhea with high morbidity and mortal-\nity to pose serious challenges in breeding and man-\nagement of RMs.4 Chronic diarrhea of RMs is \nprominently manifested by long-term and recur-\nrent diarrhea.5 Previous studies indicated that \nchronic diarrhea disease of RMs was accompanied \nby significant changes of gut microbial composi-\ntion and metabolic function.6,7 The significant \ndecrease \nof \ncarbohydrate-active \nenzyme \n(CAZyme) genes and significant increase of anti-\nbiotic resistance genes (ARGs) were found in guts \nof chronic diarrhea RMs comparing with asympto-\nmatic RMs.7 However, these changes of microbial \nabundance and diversity might not mean that \nemergence and continuation of diarrhea disease \nare caused by the increased/decreased microbiome. \nIn addition, taxonomic annotation of gut micro-\nbiome based on metagenomic short reads might \nlose many important microbial taxa due to \nCONTACT Jing Li \nljtjf@126.com"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1425
encoding: FLOAT32
metadata:
{"title": "Assembly of novel microbial genomes from gut metagenomes of rhesus macaque", "chroma:document": "Key Laboratory of Bioresources and Eco-Environment (Ministry of Education, College of Life Sciences, Sichuan \nUniversity, Chengdu, Sichuan, China; Anyun, Zhang \nzhanganyun@scu.edu.cn \nKey Laboratory of Bioresources and Eco-Environment (Ministry of \nEducation), College of Life Sciences, Sichuan University, Sichuan, China\n\u2020Contributed equally to this work\nSupplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2188848\nGUT MICROBES                                              \n2023, VOL. 15, NO. 1, 2188848 \nhttps://doi.org/10.1080/19490976.2023.2188848\n\u00a9 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, \ndistribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted \nManuscript in a repository by the author(s) or with their consent."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1426
encoding: FLOAT32
metadata:
{"title": "Mocrobial metabolites as modulators of the infant gut microbiome and host-microbiome interations in early life", "chroma:document": "REVIEW\nMicrobial metabolites as modulators of the infant gut microbiome and \nhost-microbial interactions in early life\nHenrik M. Roager\na, Catherine Stanton\nb, and Lindsay J. Hall\nc,d,e\naDepartment of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark; bAPC Microbiome Ireland, Teagasc \nMoorepark Food Research Centre, Fermoy, Co. Cork, Ireland; cGut Microbes & Health, Quadram Institute Biosciences, Norwich, UK; dIntestinal \nMicrobiome, School of Life Sciences, ZIEL \u2013 Institute for Food & Health, Technical University of Munich, Freising, Germany; eNorwich Medical \nSchool, University of East Anglia, Norwich, UK\nABSTRACT\nThe development of infant gut microbiome is a pivotal process affecting the ecology and function \nof the microbiome, as well as host health. While the establishment of the infant microbiome has \nbeen of interest for decades, the focus on gut microbial metabolism and the resulting small \nmolecules (metabolites) has been rather limited. However, technological and computational \nadvances are now enabling researchers to profile the plethora of metabolites in the infant gut, \nallowing for improved understanding of how gut microbial-derived metabolites drive microbiome \ncommunity structuring and host-microbial interactions. Here, we review the current knowledge on \ndevelopment of the infant gut microbiota and metabolism within the first year of life, and discuss \nhow these microbial metabolites are key for enhancing our basic understanding of interactions \nduring the early life developmental window.\nARTICLE HISTORY \nReceived 3 October 2022  \nRevised 3 February 2023  \nAccepted 6 March 2023 \nKEYWORDS \nMetabolites; metabolomics; \ninfants; microbiota; health; \nhost; diet\nIntroduction\nA relatively simple microbial community at birth \ndevelops into a diverse and complex microbial eco-\nsystem across the early life window1, which plays \na vital role in postnatal maturation and development \nof the endocrine, nervous and immune systems2,3."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1427
encoding: FLOAT32
metadata:
{"title": "Mocrobial metabolites as modulators of the infant gut microbiome and host-microbiome interations in early life", "chroma:document": "The gut microbiome thus has a profound influence \non both early and long-term health and \ndevelopment4,5. In addition to influencing develop-\nment and maturation of the host immune system, \nthe gut microbiota has a number of important func-\ntions in the host, including breakdown of ingested \ncomplex carbohydrates, protection against patho-\ngenic bacteria and metabolic functions including \nproduction of vitamins, short chain fatty acids \n(SCFAs) and bile acid biotransformation6. The \nimportance of neonatal bacterial colonization for \nthe growth of a healthy individual is clear and exhi-\nbits the power that the microbiome has on its host \nfrom an early stage in development.\nThe gut microbiota composition is initially known \nto be in a state of flux and consequently stabilizes, so \nthat by age 2.5\u20134 years, it begins to resemble the \ncomposition and characteristics of an adult gut7,8. In \nthis early phase, the gut microbiota is more vulnerable \nto modulation than in the adult state9, suggesting that \nthe first 1000 days of life is a critical window of \nopportunity for optimal bacterial colonization. \nDisruption to microbial development during this per-\niod is believed to have long-lasting consequences, \nimpacting on normal immune and neurocognitive \ndevelopment and has been associated with increased \nrisk of developing diseases such as asthma and meta-\nbolic syndrome later in life10,11.\nThe gut microbiota may also be modulated at \nthis critical phase in a beneficial manner. Strategies \nto optimize early microbial acquisition during this \nkey developmental window of opportunity may \nhelp to prevent and treat disease. Interventions to \nmodulate the early microbiome include the use of \nprobiotic and prebiotic interventions or combina-\ntions of both, as either synbiotics12 or postbiotics13. \nThe most promising results for probiotics have \nbeen seen in the prevention or treatment of \nCONTACT Henrik M. Roager \nhero@nexs.ku.dk"}


