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Amyotrophic lateral sclerosis as a synaptopathy

Neural Regeneration Research 2019年第2期14卷 189-192页

作者： matthew j.fogarty Department of Physiology and Biomedical Engineering Mayo Clinic School of Biomedical Sciences The University of Queensland

The synapse is an incredibly specialized structure that allows for the coordinated communication of information from one neuron to another. When assembled into circuits, steady streams of excitatory and inhibitory synaptic activity shape neural outputs. At the organismal level, ensembles of neural networks underlie behavior, emotion and memory. Disorder or dysfunctions of synapses, a synaptopathy, may underlie a host of developmental and degenerative neurological conditions. There is a possibility that amyotrophic lateral sclerosis may be a result of a synaptopathy within the neuromotor system. To this end, particular attention has been trained on the excitatory glutamatergic synapses and their morphological proxy, the dendritic spine. The extensive detailing of these dysfunctions in vulnerable neuronal populations, including corticospinal neurons and motor neurons, has recently been the subject of original research in rodents and humans. If amyotrophic lateral sclerosis is indeed a synaptopathy, it is entirely consistent with other proposed pathogenic mechanisms – including glutamate excitotoxicity, accumulation of misfolded proteins and mitochondrial dysfunction at distal axon terminals(cortico-motor neuron and neuromuscular). Further, although the exact mechanism of disease spread from region to region is unknown, the synaptopathy hypothesis is consistent with emerging die-forward evidence and the prion-like propagation of misfolded protein aggregates to distant neuronal populations. Here in this mini-review, we focus on the timeline of synaptic observations in both cortical and spinal neurons from different rodent models, and provide a conceptual framework for assessing the synaptopathy hypothesis in amyotrophic lateral sclerosis.

关键词： motor neuron motor cortex corticospinal excitotoxicity synaptic transmission dendrites dendriticspines neuromuscular junction

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Growth and survival characteristics of spa mice

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Animal Models and Experimental Medicine 2020年第4期3卷 319-324页

作者： joline E.Brandenburg matthew j.fogarty Gary C.Sieck Department of Physical Medicine and Rehabilitation Mayo Clinic College of MedicineRochesterMNUSA Department of Pediatric and Adolescent Medicine Mayo Clinic College of MedicineRochesterMNUSA Department of Physiology and Biomedical Engineering Mayo Clinic College of MedicineRochesterMNUSA School of Biomedical Sciences The University of QueenslandBrisbaneAustralia Department of Anesthesiology Mayo Clinic College of MedicineRochesterMNUSA

Characterization of growth and survival of mice displaying early onset hypertonic symptoms is critical as these animals are important for research investigating mechanisms and treatments of pediatric conditions associated with hypertonia,such as cerebral ***,most animal models of cerebral palsy reproduce risk factors for developing this condition,with most failing to develop the physical symptoms or failing to survive in the postnatal *** ***-Glrb spa/j(Gly receptor mutation)transgenic mouse(spa mouse),displays symptoms of early onset hypertonia,though little has been reported on growth and survival,with no reports of growth and survival since genotyping became *** found that the majority of spa mice display symptoms by *** mice surviving to weaning,only^9%were spa *** weaning age,spa mice had significantly lower weights than their heterozygote and wild-type *** mice that died after weaning and prior to use in experiments or being culled,48%were spa *** poor growth and decreased survival of spa mice across multiple developmental and adult ages resembled the varied survival rates observed in humans with mild or severe cerebral *** understanding of the expected survival of these mice is helpful for planning breeding and animal numbers for *** to the symptoms and timing of symptom onset,spa mice will be valuable in uncovering mechanisms and long-term effects of early onset hypertonia in order to move toward interventions for these conditions.

关键词： animal models cerebral palsy mice reproduction survival rate

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Phase transitions between tropical,subtropical,and extratropical cyclones:A review from IWTC-10

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Tropical Cyclone Research and Review 2023年第4期12卷 294-308页

作者： Kimberly Wood Wataru Yanase jack Beven Suzana j.Camargo joseph B.Courtney Chris fogarty junya Fukuda Naoko Kitabatake matthew Kucas Ron McTaggart-Cowan Michelle Simoes Reboita jacopo Riboldi The University of Arizona ArizonaUSA Meteorological Research Institute IbarakiJapan National Hurricane Center MiamiUSA Lamont-Doherty Earth Observatory Columbia UniversityPalisadesUSA Bureau of Meteorology MelbourneAustralia Canadian Hurricane Center Nova ScotiaCanada japan Meteorological Agency TokyoJapan Meteorological College ChibaJapan joint Typhoon Warning Center HonoluluUSA Environment and Climate Change Gatineau QuebecCanada Federal University of Itajuba ItajubaBrazil ETH Zurich ZurichSwitzerland

This review,which was adapted from a Tenth International Workshop on Tropical Cyclones(IWTC-10)report,discusses research findings and operational practices relevant to cyclone types and phase transitions(extratropical,subtropical,and tropical).The cyclone phase space(CPS)method is widely used in both historical investigations and real-time evaluation of cyclone type and transition;however,CPS parameter values depend on input data resolution,and universal thresholds do not currently exist to delineate when a cyclone transitions from one type to *** of phase transitions in a changing climate highlight potential latitude shifts in extratropical transition and increased potential for tropical transition,but realistic projections of future trends likely require high-resolution simulations that can capture the cyclone warm *** meteorological centers apply varied approaches to cyclone classification via CPS parameters and other criteria,some of which depend on the tropical basin,yet these approaches cannot fully address challenges in operational classification and subsequently in communicating risks associated with these phase *** recommend a multivariate historical assessment of tropical and subtropical cyclones across all basins in which they occur,including the South Atlantic Ocean and the Mediterranean Sea,to identify the potential for a more universal cyclone classification approach that meets operational needs.

关键词： Tropical cyclone Subtropical cyclone Extratropical transition Tropical transition

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A Toxicological Assessment of Endocrine Disrupting Chemicals Found in the BMW (Border, Midland and Western) Region of Ireland

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journal of Environmental Protection 2012年第4期3卷 304-315页

作者： Kathryn M. Quinn-Hosey james j. Roche Andrew M. fogarty Concepta A. Brougham Endocrine Disruption Group Department of Life and Physical Sciences School of Science Athlone Institute of Technology Athlone Co. Westmeath Ireland

A battery of tests was established to determine the oestrogenic, mutagenic and genotoxic potential of two categories of endocrine disrupting chemicals (EDCs), phthalates and alkylphenols. Diisononylphthalate (DINP), diethylhexylphthalate (DEHP), dibutylphthalate (DBP), diisododecylphthalate (DIDP) and 4-nonylphenol (4-NP) were oestrogenic in the yeast estrogen screen (YES) assay and potently oestrogenic in the MVLN and E-SCREEN assays at environmentally relevant concentrations. DINP and 4-NP were mutagenic in the Ames assay and also induced significant levels of unscheduled DNA synthesis and DNA strand breakage. Significant induction in the percentage of cells containing micronuclei was observed after treatment with DINP, DEHP and 4-NP. In addition, sewage effluents from sewage treatment plants (STPs) in the Border, Midlands and Western (BMW) region of Ireland were significantly oestrogenic in the YES assay. Moreover, analysis of levels of phthalates and alkylphenol identified in Irish rivers receiving treated effluent showed potent oestrogenicity in the YES assay. The proliferative and genotoxic ability of the phthalates and alkylphenol, and the oestrogenicity of the treated effluents reported here, is significant as these EDCs and EDCs within the effluent may play a role in the etiology of human abnormalities.

关键词： Endocrine Disrupting Chemicals (EDCs) Proliferation Transactivation Mutagenicity Genotoxicity Sewage Treatment Plant (STP) Border Midlands and Western (BMW) Region of Ireland

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Screening for Genotoxicity and Oestrogenicity of Endocrine Disrupting Chemicals <i>in Vitro</i>

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journal of Environmental Protection 2012年第8期3卷 902-914页

作者： Karthryn M. Quinn-Hosey james j. Roche Andrew M. fogarty Concepta A. Brougham Endocrine Disruption Group Department of Life and Physical Sciences School of Science Athlone Institute of Technology Athlone Co. Westmeath Ireland

A diverse range of endocrine disrupting chemicals (EDCs) was examined, using an in vitro test system, for critical events required for the onset of carcinogenesis in vivo. The initiation stage of carcinogenesis is a genotoxic process. 4-Octylphenol (alkylphenol), bisphenol A (plasticiser), coumestrol and genistein (phytoestrogens), 2,4-dichlorophe- noxyacetic acid and toxaphene (pesticides) and ethinylestradiol (synthetic hormone) were investigated for potential mutagencicity, DNA strand breakage, clastogenicity and DNA repair. Significant induction in the percentage of cells containing micronuclei was observed for all the EDCs. Toxaphene and coumestrol were mutagenic in the Ames assay. They also induced significant levels of unscheduled DNA synthesis and DNA strand breakage. Bisphenol A induced low level DNA strand breakage in HepG2 cells in the comet assay. The EDCs, with the exception of toxaphene, induced transcriptional activation in the yeast estrogen screen (YES) assay. They were potently oestrogenic in the mammalian based MVLN (transactivation) and E-SCREEN (proliferation) assays. This report on the transactivational, proliferative and genotoxic ability of the EDCs suggests that these chemicals may play a role in the etiology of male and female reproductive cancers.

关键词： Four Endocrine Disrupting Chemicals (EDCs) Proliferation Mutagenicity DNA Strand Breakage Comet Assay DNA Repair Unscheduled DNA Synthesis Assay (UDS) E-SCREEN Assay YES Assay MVLN Assay

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胸部平片评分单独或联合其他风险评分预测COVID-19预后

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国际医学放射学杂志 2022年第2期 237-238页

作者： I.Au-Yong Y.Higashi E.Giannotti A.fogarty j.R.Morling M.Grainge 朱珍

摘要放射学所显示的严重程度可能有助于预测新型冠状病毒肺炎（COVID-19）病人的病情恶化和结局。目的评估3种胸部平片报告系统[肺水肿（RALE）、Brixia和阴影百分比

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A Toxicological Assessment of Endocrine Disrupting Chemicals Found in the BMW (Border, Midland and Western) Region of Ireland

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journal of Environmental Protection（环境保护） 2012年第4期

作者： Kathryn M. Quinn-Hosey james j. Roche Andrew M. fogarty Concepta A. Brougham

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INTRASPINAL CONNECTIONS OF DORSAL COLUMN POSTSYNAPTIC NEURONS IN THE CAT——A PHYSIOLOGICAL ANALYSIS

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Science China Chemistry 1985年第9期28卷 972-978页

作者：吕国蔚,GARY j.BENNETT,NOZOMU NISHIKAWA,MARVIN j.HOFFERT,RONALD DUBNER Department of Neurophysiology Beijing Second Medical College China Neurobiology and Anesthesiology Branch National Institute of Dental Research National Institutes of Health USA Neurobiology and Anesthesiology Branch National Institute of Dental Research National Institutes of Health USA Department of Anesthesiology Shiga University of Medical Seience Shiga japan Neurobiology and Anesthesiology Branch National Institute of Dental Research National Institutes of Health USA Department of Neurology Univeraity of Wisenonsin Medieal School Madison Wisconsin 53792 U.S.A Neurobiology and Anesthesiology Branch National Institute of Dental Research National Institutes of Health USA

Dorsal column postsynaptic (DCPS) neurons in the dorsal horn of the spinal cord have been identified by antidromic stimulation and intracellularly recorded in anesthetized cats. In about one-half of the cells, the antidromic stimulus evokes only an antidromic potential. This potential sometimes has an atypical shape due to penetration-induced depolarization. Atypieal potentials arc converted into typical antidromic spike potentials after intracellular injection of hyperpolarizing current. In the other one-half, the antidromic potentials are followed by postsynaptic activity. Intracellular analysis indicates that this postsynaptic activity is generated largely by activation of the intraspinal collaterals of A-beta primary afferents that are ascending the dorsal columns. Part of this postsynaptic activity has been produced monosynaptically. Polysynaptic responses are also evident; these are thought to be initiated by A-beta axons, desending axons from neurons in the dorsal column nuclei, or the local coll

关键词： A PHYSIOLOGICAL ANALYSIS

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Exploring nationally and regionally defined models for large area population mapping

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International journal of Digital Earth 2015年第12期8卷 989-1006页

作者： A.E.Gaughan F.R.Stevens C.Linard N.N.Patel A.j.Tatem Department of Geography and Geosciences University of LouisvilleLouisvilleKYUSA Biological Control and Spatial Ecology UniversitéLibre de BruxellesBrusselsBelgium Department of Geography and Geoinformation Science George Mason UniversityFairfaxVAUSA Department of Geography and Environment University of SouthamptonSouthamptonUK fogarty International Center National Institutes of HealthBethesdaMDUSA Flowminder Foundation StockholmSweden

Interactions between humans,diseases,and the environment take place across a range of temporal and spatial scales,making accurate,contemporary data on human population distributions critical for a variety of *** for disaggregating census data to finer-scale,gridded population density estimates continue to be refined as computational power increases and more detailed census,input,and validation datasets become ***,the availability of spatially detailed census data still varies widely by *** this study,we develop quantitative guidelines for choosing regionally-parameterized census count disaggregation models over country-specific *** examine underlying methodological considerations for improving gridded population datasets for countries with coarser scale census data by investigating regional versus country-specific models used to estimate density surfaces for redistributing census *** is given to the spatial resolution of input census data using examples from East Africa and Southeast *** suggest that for many countries more accurate population maps can be produced by using regionally-parameterized models where more spatially refined data exists than that which is available for the focal *** study highlights the advancement of statistical toolsets and considerations for underlying data used in generating widely used gridded population data.

关键词： human population modeling random forest regression dasymetric mapping gridded population datasets

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Using Non-Human Animals in Research:An American Perspective

Using Non-Human Animals in Research:An American Perspective

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科研伦理培训与伦理审查能力建设专题研讨会

作者： Michael j.Zigmond University of Pittsburgh

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