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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase cγ-ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

A poetics of“Wind in a Box”

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Language and Semiotic Studies 2024年第3期10卷 408-414页

作者： john robinson West Virginia Department of Education CharlestonUSA

This essay is a re-application of the language codes of Roland Barthes and Jonathan culler’s concept for Structuralist *** approach I use explores the codes demonstrated in Barthes’well-known text,S/Z with slight modifications for their application to *** concepts borrowed from *** are from his book of the same title:Structuralist Poetics:Structuralism,Linguistics and the Study of Literature(cornell University Press,1975).culler’s main argument is that there must be other,un-attempted strategies combined with conventional approaches in literature of that time *** answer to this problem was to develop a set of linguistic-based concepts to compensate for the reader in the analysis of literary works.I have applied in this essay my approach based on culler’s methodology and the language codes of Roland Barthes:semantic,symbolic,cultural-referential,actional and hermeneutic.I apply culler’s concepts to a reading of poetry followed by an application of the language codes as a further development of my work in revitalizing this never-before applied method.

关键词： poetics literary theory poetry

Ground of a Theory:The Language codes of Roland Barthes and American critical Structuralism

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Language and Semiotic Studies 2021年第1期7卷 79-106页

作者： john Timothy robinson The Woven Tale Press

This paper is an application of johnathan culler’s Structuralist Poetics from 1975 combined with the language codes of Roland Barthes which he developed in his study of S/Z to the close reading of ***’s main argument is that there must be another strategy combined with all major approaches in Structuralist thought in that time *** answer to this problem was to develop a set of strategies or concepts to compensate for the reader in the analysis of literary works.I outline in this essay my approach based on the language codes of Roland Barthes:semantic,symbolic,cultural-referential,actional and *** a brief discussion of my understanding and contextualization of Structuralism today for this particular genre application,I apply the concepts to a reading of the famous William carlos Williams’poem,"The Red Wheelbarrow"as a test-case application of the concepts.

关键词： poetry literary theory Structuralism poetics

Association between thyroid function and gallstone disease

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World Journal of Gastroenterology 2005年第35期11卷 5530-5534页

作者： Henry Vlzke Daniel M robinson Ulrich john Ernst Moritz Arndt University Greifswald Institute of Epidemiology and Social Medicine Walther Rathenau Str. 48 D-17487 Greifswald Germany Ernst Moritz Arndt University Greifswald Department of Medicine B Friedrich Loeffler Str. 23a D-17487 Greifswald Germany

AIM： To investigate those associations using data of the population-based Study of Health in Pomerania. METHODS： A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis. RESULTS： There were 385 persons （10.3%） with low （〈0.3 mIU/L）, 3 321 persons （88.6%） with normal and 43 persons （1.2%） with high serum TSH levels （〉3 mIU/L）. The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis （OR 3.77; 95%-cI 1.06-13.41; P〈0.05）. Also among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH （OR 1.40; 95%-cI 0.96-2.02; P= 0.07）. In the female population, no such relation was identified. cONcLUSION： There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.

关键词： Thyroid function Gallstones cholelithiasis SHIP

cold plasma redistribution throughout geospace

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Science china(Technological Sciences) 2016年第9期59卷 1340-1345页

作者： Foster john c. Massachusetts Institute of Technology Haystack Observatory

The redistribution of the electrically charged cold plasma of ionospheric origin involves the equatorial,low,mid,auroral,and polar-latitude regions in a multi-step,system-wide process linking the regions of *** with ground and space-based instruments characterize the geospace plume-regularly occurring channels of enhanced plasma density flowing at both ionospheric and magnetospheric *** in the SAPS channel transports the eroded material to the noontime cusp in the ionosphere and to the dayside magnetopause at high *** the fluxes of cold plume plasma traverse the cusp and enter the polar cap,they form the polar tongue of *** the cusp the plume plasma provides a rich source of heavy ions for the magnetospheric injection and acceleration via the mechanisms operative on those field lines.

关键词： plasmasphere ionosphere geospace GPS TEc ionospheric electric field plume

A Pragmatic Observational Feasibility Study on Integrated Treatment for Musculoskeletal Disorders：Design and Protocol

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chinese Journal of Integrative Medicine 2016年第2期22卷 88-95页

作者：胡晓阳 john Hughes Peter Fisher Ava Lorenc Rachel Purtell A-La Park Nicola robinson Faculty of Health and Social care London South Bank Universiy Royal London Hospital for Integrated Medicine University College London Hospital National Healt Service Trust Faculty of Health and Social care London South BankUniversiy Patient representative Personal Social Services Research Unit Health and Social Carethe London School of Economics and Political Science

Background：Musculoskeletal disorders（MSD） comprise a wide range of conditions,associated with an enormous pain and impaired mobility,and are affecting people＇s lives and *** of musculoskeletal disorders typically involves a multidisciplinary team *** findings have been found in previous studies evaluating the effectiveness of complementary therapies,though little attention has been paid to evaluating of the effectiveness of integrated packages of care combining conventional and complementary approaches for musculoskeletal conditions in a National Health Service（NHS） ***：To determine the feasibility of all aspects of a pragmatic observational study designed：（1） to evaluate the effectiveness and cost effectiveness of integrated treatments for MSDs in an integrated NHS hospital in the UK;（2） to determine the acceptability of the study design and research process to patients;（3） to explore patients＇ expectation and experience of receiving integrated ***：This is an observational feasibility study,with 1-year recruitment and 1-year follow-up,conducted in Royal London Hospital for Integrated Medicine,University college London Hospital Trust,*** eligible patients with MSDs newly referred to the hospital were included in the *** are integrated packages of care（conventional and complementary） as currently provided in the ***-36 Health Survey,short form Brief Pain Inventory,Visual Analogue Scale,and modified client Service Receipt Inventory will be assessed at 4/5 time ***-structured interview/focus group will be carried out before treatment,and 1 year after commence of ***：We intend to conduct a pragmatic observational study of integrated medical treatment of MSDs at a public sector *** will inform the design of a future trial including recruitment,retention,suitability of the outcome measures and patients experiences.

关键词： integrated medicine musculoskeletal disorders feasibility study mixed method

Recurrent ectopic pancreatitis of the jejunum and mesentery over a 30-year period

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Hepatobiliary & Pancreatic Diseases International 2011年第2期10卷 218-220页

作者： john cT Wong charlotte robinson Edward c Jones Alison Harris charles Zwirewich Robert Wakefield Richard K Simons Eric M Yoshida Department of Medicine Department of Medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Department of Radiology Department of Medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Department of Pathology and Laboratory Medicine Department of Medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Department of Surgery Department of Medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9 Division of Gastroenterology Department of Medicine 2775 Laurel StreetUniversity of British Columbia VancouverBritish ColumbiaCanadaV5Z 1M9

BAcKGROUND:Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position,with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography(cT)and magnetic resonance cholangiopancreatography(MRcP),and confirmed on histological review of the resection. METHODS:A 67-year-old woman presented with clinical symptoms and biochemical evidence of *** had similar episodes over the past 30 years with unrevealing investigations,and was concluded to have idiopathic pancreatitis. She underwent cT and MRcP,with findings suggestive of ectopic pancreas,a diagnosis confirmed on histology of the resection. RESULTS:MRcP identified a mass in the proximal small bowel mesentery isointense to the native pancreas,with a small duct draining into a proximal jejunal *** resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans,an occasional ductular structure,and admixed areas of adipose *** patient remained asymptomatic with normal biochemistry six months post-operatively. cONcLUSION:In an individual with abdominal pain,elevated serum amylase/lipase,but imaging findings of a normal native pancreas,ectopic pancreatitis should be considered,and can be evaluated by cT and MRcP.

关键词： ectopic pancreas gastrointestinal tract endoscopic ultrasound computed tomography magnetic resonance cholangiopancreatography

Metagenomics: Facts and Artifacts, and computational challenges

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Journal of computer Science & Technology 2010年第1期25卷 71-81页

作者： john c. Wooley 叶玉珍 center for Research on BioSystems Calit2 University of California San Diego School of Informatics and computing Indiana University

Metagenomics is the study of microbial communities sampled directly from their natural environment, without prior culturing. By enabling an analysis of populations including many （so-far） unculturable and often unknown microbes, metagenomics is revolutionizing the field of microbiology, and has excited researchers in many disciplines that could benefit from the study of environmental microbes, including those in ecology, environmental sciences, and biomedicine. Specific computational and statistical tools have been developed for metagenomic data analysis and comparison. New studies, however, have revealed various kinds of artifacts present in metagenomics data caused by limitations in the experimental protocols and/or inadequate data analysis procedures, which often lead to incorrect conclusions about a microbial community. Here, we review some of the artifacts, such as overestimation of species diversity and incorrect estimation of gene family frequencies, and discuss emerging computational approaches to address them. We also review potential challenges that metagenomics may encounter with the extensive application of next-generation sequencing （NGS） techniques.

关键词： metagenomics next-generation sequencing (NGS) taxonomic/functional profiling statistical approaches comparative metagenomics

Impact of androgen deprivation therapy on sexua function： a response

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Asian Journal of Andrology 2012年第5期14卷 793-794页

作者： Erik Wibowo Richard Wassersug Karen Warkentin Lauren Walker john robinson Lori Brotto Thomas johnson Department of Anatomy&Neurobiology Dalhousie UniversityHalifaxNS B3H 4R2Canada Men's Health Initiative of B.c. Department of Urologic SciencesUniversity of British ColumbiaVancouverBC V5Z 1M9Canada Department of Biology Boston UniversityBostonMA 02215USA Department of Psychology University of CalgaryCalgaryAB T2N 1N4Canada Department of Psychosocial Resources Tom Baker Cancer CentreCalgaryAB T2S 3C1Canada UBc Sexual Health Lab Gordon&Leslie Diamond Health Care CentreDepartment of Obstetrics/GynecologyDivision of Gynecologic OncologyVancouverBC V5Z 1M9Canada Department of Anthropology California State UniversityFultonCA 95439-0050USA

Dear Editors, We appreciate the growing patients and survivors. Mazzola interest in sexual health for cancer and Mulhall＇s recent paper,a however, creates the impression that rewarding sex is not possible for prostate cancer patients on androgen deprivation therapy （ADT）. This impression, we believe, is not scientifically justified,

关键词： androgen therapy estosterone