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Glutamate transporters, EAAT1 and EAAT2, are potentially important in the pathophysiology and treatment of schizophrenia and affective disorders

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World Journal of Psychiatry 2018年第2期8卷 51-63页

作者： Georgia M Parkin Madhara Udawela Andrew Gibbons brian dean Molecular Psychiatry Laboratory the Florey Institute of Neuroscience and Mental Health CRC for Mental Health Research Centre for Mental Health the Faculty of Health Arts and Design Swinburne University

Glutamate is the predominant excitatory neurotransmitter in the human brain and it has been shown that prolonged activation of the glutamatergic system leads to nerve damage and cell death. Following release from the pre-synaptic neuron and synaptic transmission, glutamate is either taken up into the presynaptic neuron or neighbouring glia by transmembrane glutamate transporters. Excitatory amino acid transporter(EAAT) 1 and EAAT2 are Na+-dependant glutamate transporters expressed predominantly in glia cells of the central nervous system. As the most abundant glutamate transporters, their primary role is to modulate levels of glutamatergic excitability and prevent spill over of glutamate beyond the synapse. This role is facilitated through the binding and transportation of glutamate into astrocytes and microglia. The function of EAAT1 and EAAT2 is heavily regulated at the levels of gene expression, post-transcriptional splicing, glycosylation states and cell-surface trafficking of the protein. Both glutamatergic dysfunction and glial dysfunction have been proposed to be involved in psychiatric disorder. This review will present an overview of the roles that EAAT1 and EAAT2 play in modulating glutamatergic activity in the human brain, and mount an argument that these two transporters could be involved in the aetiologies of schizophrenia and affective disorders as well as represent potential drug targets for novel therapies for those disorders.

关键词： Glia Excitatory amino acid transporter Psychiatry Affective disorders Glutamate transporter Glutamate Schizophrenia

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湍流流动中鲨鱼皮表面流体减阻研究进展

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力学进展 2012年第6期42卷 821-836页

作者： brian dean Bharat Bhushan 杨绍琼(译) 李山(译) 田海平(译) 李一凡(译) 姜楠(校) Nanoprobe Laboratory for Bio-and Nanotechnology and Biomimetics(NLBB) Ohio State University 天津大学机械工程学院力学系天津大学流体力学实验室沟槽减阻研究小组天津大学机械工程学院力学系天津市现代工程力学重点实验室

快速游动的鲨鱼,其皮肤表面沿流动方向有序地排列着沟槽状结构,人们认为这种结构能在湍流流动中减小表面摩擦阻力.人们仿真这种生物结构来进行实验研究和应用,通过复制和改善鲨鱼皮肤表面沟槽状结构,使得摩擦阻力最大减小了近10%.在实... 详细信息

快速游动的鲨鱼,其皮肤表面沿流动方向有序地排列着沟槽状结构,人们认为这种结构能在湍流流动中减小表面摩擦阻力.人们仿真这种生物结构来进行实验研究和应用,通过复制和改善鲨鱼皮肤表面沟槽状结构,使得摩擦阻力最大减小了近10%.在实验和模拟仿真中,人们不断讨论和研究湍流流动阻力的形成机制和沟槽减阻的理论特性.本文综述了沟槽减阻理论特性的一些研究方法,并且归纳定义了沟槽减阻最优几何形状及其尺寸;详细考虑流体流动的特点,给出了一种用来选择最优沟槽形状及其尺寸的方法;综述了目前的沟槽加工制造技术.由于鲨鱼皮肤表面存在少量黏液,从仿生学的角度,文章最后综述并展望了通过局部应用疏水性材料来改变沟槽附近流场属性,从而达到更大程度上减小阻力的目标.

关键词：鲨鱼皮肤减阻沟槽仿生学湍流流动疏水性

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Allosteric modulation of cholinergic system:Potential approach to treating cognitive deficits of schizophrenia

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World Journal of Pharmacology 2016年第1期5卷 32-43页

作者： Shaun Hopper Madhara Udawela Elizabeth Scarr brian dean the Florey Institute of Neuroscience and Mental Health the University of Melbourne Department of Psychiatry the University of Melbourne

Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics ameliorate positive symptoms, they are largely ineffective in improving negative symptoms and cognitive deficits. The cholinergic neurotransmitter system heavily influences cognitive function and there is evidence that implicates disruption of the central cholinergic system in schizophrenia. Historically, targeting the cholinergic system has been impeded by poor selectivity leading to intolerable side effects warranting the need to develop more targeted therapeutic compounds. In this review we will summarise evidence supporting the roles of the cholinergic system, particularly the muscarinic M1 receptor, in the pathophysiology of schizophrenia and discuss the potential of a promising new class of candidate compounds, allosteric ligands, for addressing the difficulties involved in targeting this system. The body of evidence presented here highlights the dysfunction of the cholinergic system in schizophrenia and that targeting this system by taking advantage of allosteric ligands is having clinically meaningful effect on cognitive deficits.

关键词： Central nervous system Antipsychotic Allosteric Cholinergic Schizophrenia Mutagenesis Cognition Muscarinic

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Biomarkers in schizophrenia:A focus on blood based diagnostics and theranostics

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World Journal of Psychiatry 2016年第1期6卷 102-117页

作者： Chi-Yu Lai Elizabeth Scarr Madhara Udawela Ian Everall Wei J Chen brian dean the Florey Institute of Neuroscience and Mental Health Institute of Epidemiology and Preventive Medicine College of Public HealthNational Taiwan University Center of Genomic Medicine National Taiwan University Department of Psychiatry the University of Melbourne

Identifying biomarkers that can be used as diagnostics or predictors of treatment response(theranostics) in people with schizophrenia(Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophreniaassociated phenotype. We sorted the studies into six categories which include:(1) brain-derived neurotrophic factor;(2) inflammation and immune function;(3) neurochemistry;(4) oxidative stress response and metabolism;(5) epigenetics and micro RNA; and(6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, bloodoriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development.

关键词： Schizophrenia Peripheral blood Biomarker Diagnostics Schizophrenia-associated phenotype Treatment response Clinical courses

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Identifying sex-specific differences in the carotid revascularisation literature:findings from a scoping review

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Stroke & Vascular Neurology 2021年第3期6卷 496-499,I0085-I0096页

作者： Vignan Yogendrakumar Michel Shamy brian Dewar dean A Fergusson Dar Dowlatshahi Candyce Hamel Sophia Gocan Mark Fedyk Jean-Louis Mas Peter Rothwell Virginia Howard Olena Bereznyakova On behalf of the WoW-CAD Investigators Department of Medicine Division of Neurology and Ottawa Hospital Research InstituteUniversity of OttawaOttawaOntarioCanada Epidemiology Program Ottawa Hospital Research InstituteOttawaOntarioCanada Stroke Prevention Clinic Ottawa HospitalOttawaOntarioCanada Bioethics Program UC Davis Department of MedicineSacramentoCaliforniaUSA Universite Paris Descartes Faculte de Medecine Site Cochin Parislle-de-FranceFrance Service de Neurologie Hôital Sainte-AnneParisFrance The University of Alabama at Birmingham School of Medicine BirminghamAlabamaUSA School of Public Health University of Alabama at BirminghamBirminghamAlabamaUSA 不详

Objective No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female *** this scoping review,we aimed to identify all randomised controlled trials(RCTs)that reported sex-specific outcomes for patients who underwent carotid revascularisation,and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female ***,setting and participants We systematically searched Medline,Embase,Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting,or any revascularisation(endarterectomy or stenting)with medical therapy in patients with symptomatic high-grade(>50%)carotid *** From 1537 references examined,27 eligible studies were ***-specific outcomes were reported in 13 *** patient characteristics of enrolled female patients were reported in 2 of those 13 *** outcomes reported included stroke and death,however,there was significant heterogeneity in the reporting of both periprocedural and long-term ***-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical *** events were not reported by *** Only half of the previously published RCTs and systematic reviews report sex-specific *** analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited.

关键词： carotid stenosis finding

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Eccentric exercise in the prevention of patellofemoral pain in high-volume runners:A rationale for integration

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Sports Medicine and Health Science 2021年第2期3卷 119-124页

作者： brian Faller dean Bonneau Liana Wooten Dhinu J.Jayaseelan The George Washington University.Department of Health Human Function and Rehabilitation Sciences Washington DC20006USA

Patellofemoral pain(PFP)is a common overuse condition seen in high-volume runners,such as military *** is commonly prescribed,with benefit,for the rehabilitation of individuals with ***,a sub-stantial number of individuals with the condition do not achieve an optimal outcome,suggesting the condition can be difficult and *** the challenging nature of the condition,and the risk of developing PFP in high-volume runners,it seems logical to investigate options for injury *** exercise has been useful in the prevention of some pathologies so its utility in preventing PFP should be *** evidence regarding prevention programs for PFP are *** exercise programs for PFP have not been well described or reported,and questions remain regarding their *** on available evidence or lack thereof,and known physiological and clinical effects of eccentric exercise,suggestions for integration of eccentric exercise into PFP prevention programs are *** exercise may be useful for PFP prevention from a theoretical framework however additional longitudinal cohort studies would be useful in determining its utility.

关键词： Anterior knee pain Exercise Injury prevention Patellofemoral joint

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Parallelization of Diagnostics for Climate Model Development

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Journal of Software Engineering and Applications 2016年第5期9卷 199-207页

作者： Jim McEnerney Sasha Ames Cameron Christensen Charles Doutriaux Tony Hoang Jeff Painter brian Smith Zeshawn Shaheen dean Williams Lawrence Livermore National Laboratory Livermore California USA University of Utah Salt Lake City Utah USA Oak Ridge National Laboratory Oak Ridge Tennessee USA

The parallelization of the diagnostics for climate research has been an important goal in the performance testing and improvement of the diagnostics for the Department of Energy’s (DOE’s) Accelerated Climate Modeling for Energy (ACME) project [1]. The primary mission of the ACME project is to build and test the next-generation Earth system model for current and future generations of computing systems operated by the DOE office of science computing facilities, including the envisioned exascale systems foreseen in the early part of the next decade. As part of the underpinning workflow environment, a diagnostics, model metrics, and intercomparison Python framework, called UVC Metrics was created to aid in testing and production execution of the model. This framework builds on common methods and similar metrics to accommodate and diagnose individual component models, such as atmosphere, land, ocean, sea ice, and land ice. This paper reports on initial parallelization of UVC Metrics for the atmosphere model component using two popular frameworks: MPI and SPARK. A timing study is presented to assess the performance of each method in which significant improvement was achieved for both frameworks despite I/O contentions with NFS. The advantages and disadvantages of each framework are also presented.

关键词： Climate Diagnostics Parallel MPI SPARK

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Impact of community-based exercise program participation on aerobic capacity in women with and without breast cancer

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World Journal of Clinical Oncology 2021年第6期12卷 468-481页

作者： Jordan T Lee Chad W Wagoner Stephanie A Sullivan dean J Amatuli Kirsten A Nyrop Erik D Hanson Lee Stoner brian C Jensen Hyman B Muss Claudio L Battaglini Department of Exercise and Sport Science University of North Carolina at Chapel HillChapel HillNC 27599United States Lineberger Comprehensive Cancer Center University of North Carolina at Chapel HillChapel HillNC 27599United States Department of Medicine Division of CardiologyUniversity of North Carolina at Chapel HillChapel HillNC 27599United States Lineberger Comprehensive Cancer Center University of North CarolinaChapel HillNC 27599United States

BACKGROUND Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors(BCS)has come largely from intervention studies conducted in laboratory *** is an increasing need to translate to community-type settings,but the efficacy of those interventions using gold standard evaluation is not *** To investigate whether similar improvement in aerobic capacity(maximal oxygen consumption[VO2])measured with gold standard testing can be achieved through a community-based setting in *** A peak cardiopulmonary exercise test(VO2peak),6-min walk test(6MWT),and timed up and go test(TUG)were assessed pre-and post-16 wk of progressive intensity aerobic and strength training exercise at a community *** The sample consisted of 31 early BCS(<1 year since treatment completion)and 15 controls(CTLs).Both groups significantly improved VO2peak(+1.2 mL/kg/min;P=0.030),6MWT(+35 meters;P<0.001),and TUG(-0.44 s;P<0.01)following *** groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by+10 watts more than the CTLs(P=0.020).Average exercise attendance was 71%(34 of 48 possible days),but compliant days averaged only 60%of total days for aerobic,and<40%for strength in both *** Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled *** research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

关键词： Aerobic capacity Breast cancer Community-based Exercise Physical function

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Beta-adrenergic receptor polymorphisms: A basis for pharmacogenetics

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World Journal of Cardiovascular Diseases 2013年第6期3卷 406-411页

作者： Efstratios K. Theofilogiannakos Konstantinos dean Boudoulas brian E. Gawronski Taimour Y. Langaee Timotheos G. Kelpis Antonios A. Pitsis Julie A. Johnson Harisios Boudoulas Agios Lukas Hospital Thessaloniki Greece The Ohio State University Division of Cardiovascular Medicine Columbus Ohio USA The Ohio State University Division of Cardiovascular Medicine Columbus Ohio USA Aristotelian University of Thessaloniki Thessaloniki Greece University of Florida Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics Gainesville Florida USA

Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.

关键词： β1 and β2-Adrenergic Receptor Polymorphism Ethnic Variability

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太极拳对健康老年人身体平衡功能影响的研究综述

太极拳对健康老年人身体平衡功能影响的研究综述

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中国康复医学会运动疗法分会第十一届全国康复学术大会学术会议

作者： Colleen A.Byrne Fairlie K.Fraser brian J.Horswill Lindsay V.Trimble 王亚昆 Elizabeth dean B.Sc.Chemistry MPT B.Sc.Kinesiology MPT B.Music MPT B.Sc.Human Kinetics MPT B.Sc.Biology MPTFraser Health AuthorityBurnabyBC Faculty of Medicine University of British ColumbiaVancouverBritish Columbia Dr.

目的:文综合太极拳对健康老年人身体平衡功能影响的国内外研究报道,旨在促进知识和文化交流,为太极拳在该领域的研究提供方向。通过检验并比较不同的平衡功能测试,为太极拳的功效做出全面的综合描述。方法:英文文献电脑检索数据库Medlin...

目的:文综合太极拳对健康老年人身体平衡功能影响的国内外研究报道,旨在促进知识和文化交流,为太极拳在该领域的研究提供方向。通过检验并比较不同的平衡功能测试,为太极拳的功效做出全面的综合描述。方法:英文文献电脑检索数据库Medline,CINAHL,PEDro,Sport discus,Embase,EMB Reviews,检索工作始于2007年4月,止于2008年8月。检索关键词tai chi/tai ji/tai chi chuan(太极拳),postural stability/posture/postural equilibrium(姿势稳定性),balance/dynamic equilibrium(平衡),elderly/aging/aged/adult(老年人)。

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