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Targeting TrkB–pSD-95 coupling to mitigate neurological disorders

2008年

作者： john c.p. goldberg Anthony J. Sebok Benjamin c. Zipursky

来源：畅想之星图书光盘版（南... 评论

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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 rec.p.or 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 rec.p.or 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.p.asticity TrkB

Electrical stimulation and denervated muscles after spinal cord injury

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Neural Regeneration Research 2020年第8期15卷 1397-1407页

作者： Subhalakshmi chandrasekaran john Davis Ines Bersch Gary goldberg Ashraf S.Gorgey Spinal cord Injury and Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Swiss paraplegic centre NottwilSwitzerland Institute of clinical Sciences Department of Orthopedics at the University of GothenburgGothenburgSweden Department of physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVAUSA Electrodiagnostic center Hunter Holmes McGuire VA Medical CenterRichmondVAUSA

Spinal cord injury(ScI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous *** morphological changes may put individuals with ScI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and ***,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in ScI individuals with lower motor neuron ***,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following *** pulse width stimulation(LpWS)technique is an upcoming method of stimulating denervated *** primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated *** parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and *** use of electrical stimulation in animal and human models induces muscle *** in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle *** studies have shown similar outcomes,identifying the use of LpWS as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle ***,displaying promise is an effective future stimulation *** summary,LpWS is a novel stimulation technique for denervated muscles in humans with *** studies on LpWS of denervated muscles will help in translating

关键词： denervation DXA electrical stimulation LMN injury LpWS MRI spinal cord injury stimulation parameters

A reverse Denjoy theorem Ⅲ

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Science china Mathematics 2010年第3期53卷 657-662页

作者： FENTON p. c. ROSSI john Department of Mathematics and Statistics University of Otago Department of Mathematics Virginia Polytechnic Institute and State University

Suppose that c 1 and c 2 are two simple curves joining 0 to ∞, non-intersecting in the finite plane exc.p. at 0 and enclosing a domain D which is such that, for all large r, the set {θ : re iθ∈ D} has measure at most 2α, where 0 ppose also that u is a non-constant subharmonic function in the plane such that u(z) = Φ(|z|) for all large z ∈ c 1 ∪ c 2 ∪～D, where Φ(|z|) is a convex, non-decreasing function of |z| and ～D is the complement of D. Let A D (r, u) = inf{u(z) : z ∈ D and |z| = r}. It is shown that if A D (r, u) = O(1) then lim inf r→∞ B(r, u)/r π/(2α) > 0.

关键词： Denjoy conjecture subharmonic function tract

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 c.p.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

Investigation of Terminal Group Effect on Electron Transport Through Open Molecular Structures

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communications in Theoretical physics 2013年第5期59卷 649-654页

作者： c. preferencial Kala p. Aruna priya D. john Thiruvadigal Department of physics and Nano Technology Center for Materials Science and NanodevicesSRM University Department of Electronics and communication Engineering Center for Materials Science and NanodevicesSRM University

The effect of terminal groups on the electron transport through metal-molecule-metal system has been investigated using nonequilibrium Green’s function (NEGF) formalism combined with extended Huckel theory (EHT). Au-molecule-Au junctions are constructed with borazine and BcN unit structure as core molecule and sulphur (S), oxygen (O), selenium (Se) and cyano-group (cN) as terminal groups. The electron transport characteristics of the borazine and BcN molecular systems are analyzed through the transmission spectra and the current-voltage curve. The results demonstrate that the terminal groups modifying the transport behaviors of these systems in a controlled way. Our result shows that, selenium is the best linker to couple borazine to Au electrode and oxygen is the best one to couple BcN to Au electrode. Furthermore, the results of borazine systems are compared with that of BcN molecular systems and are discussed. Simulation results show that the conductance through BcN molecular systems is four times larger than the borazine molecular systems. Negative differential resistance behavior is observed with borazine-cN system and the saturation feature appears in BcN systems.

关键词： molecular electronics extended Huckel theory (EHT) nonequilibrium Green’s function (NEGF) quantum transport

Efficacy of infliximab in acute severe ulcerative colitis:A single-centre experience

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World Journal of Gastroenterology 2013年第7期19卷 1091-1097页

作者： Stephen J Halpin p john Hamlin Daniel p Gree Lisa Warren Alexander c Ford Leeds Gastroenterology Institute St.James's University HospitalLeedsWest Yorkshire LS9 7TFUnited Kingdom Leeds Gastroenterology Institute St.James's University HospitalLeedsWest Yorkshire LS9 7TFUnited Kingdom r Leeds Institute of Molecular Medicine University of LeedsLeedsWest Yorkshire LS9 7TFUnited Kingdom

AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical ***:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were *** were extracted from clinical records in order to assess response to IFX *** primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse *** and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were ***:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative *** median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with p,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of ***,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of *** was one death from post-operative sepsis,20 d after a single IFX *** rates were generally lower among those "bridging" to *** 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study *** predictors of response were ***:IFX is effective for acute severe ulcerative colitis in real-life clinical ***-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.

关键词： Ulcerative colitis Severe Azathioprine Infliximab Remission

A validation of WEpp water quality routines in uniform and nonuniform agricultural hillslopes

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International Soil and Water conservation Research 2024年第3期12卷 487-505页

作者： Ryan p.McGehee Dennis c.Flanagan Bernard A.Engel john E.Gilley Department of Agricultural and Biosystems Engineering Iowa State University4352 Elings Hall605 Bissel RoadAmesIA50011USA USDA-Agricultural Research Service National Soil Erosion Research Laboratory275 South Russell StreetWest LafayetteIN47907USA Department of Agricultural and Biological Engineering Purdue University225 South University StreetWest LafayetteIN47907USA USDA-Agricultural Research Service Agroecosystem Management Research UnitRoom 238Chase HallUniversity of NebraskaLincolnNE68583USA

current watershed-scale,nonpoint source pollution models do not represent the processes and impacts of agricultural best management practices on water quality with sufficient detail.A Water Erosion pre-diction project-Water Quality(WEpp-WQ)model was recently developed which is c.p.ble of simulating nonpoint source pollutant transport in nonuniform hillslope conditions such as those with ***,WEpp-WQ has not been validated for these conditions,and prior validation work only eval-uated calibrated performance rather than uncalibrated performance,with the latter being most relevant to model *** study evaluated uncalibrated and calibrated model performance in two plot-scale,artificial rainfall studies.179 observations were compared to corresponding WEpp-WQ simulations of runoff,sediment yield,and soluble and particulate nutrient forms for both nitrogen and *** validation results were mixed for the different field conditions,model configurations,and prediction ***-Sutcliffe Efficiencies for uncalibrated simulations of uniform conditions were generally greater than 0.6 exc.p. for soluble nitrogen predictions which were *** of nonuniform conditions were generally'unsatisfactory'exc.p. for runoff predictions which were quite good(NSE=0.78).performance was improved substantially for almost all endpoints with *** exc.p.ions to this occurred because the objective function for calibration was based on log-space differences so as to more equally-weight calibration of unsaturated conditions that tend to produce lesser runoff volumes and sediment *** results for both uniform and nonuniform condi-tions were generally'satisfactory'or'good'according to widely acc.p.ed model performance criteria.

关键词： Water quality Nonpoint Validation Vegetative filter strip Best management practice WEpp

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 disc.p.ines 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

Systematic review of single stage revision for prosthetic joint infection

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World Journal of Orthopedics 2020年第12期11卷 559-572页

作者： Zachary c Lum christopher Thomas Holland john p Meehan Department of Orthopaedic Surgery Davis Medical CenterUniversity of CaliforniaSacramentoCA 95817United States Department of Orthopaedics University of CaliforniaDavis Medical CenterSacramentoCA 95817United States

While advanced technology,increased medical knowledge and improved surgical technique has improved patient outcomes in total joint arthroplasty,prosthetic joint infection still remains one of the leading causes of increased healthcare costs,medical resources and societal burdens in orthopaedic *** stage arthroplasty revision remains the gold standard for treatment of prosthetic joint *** of single stage revision arthroplasty for infection argue that it results in lower healthcare costs while improving patient reported functional outcomes and with equivalent success *** we review the history of single stage revision arthroplasty,discuss the key princ.p.es,highlight the indications and contraindications,and review the reported outcomes with a focus on future developments of single stage revision arthroplasty for hip and knee periprosthetic joint infections.

关键词： prosthetic joint infection Single stage Revision total joint arthroplasty Total knee arthroplasty Infection