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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

第十二届中国体视学与图像分析学术会议

作者： john m.basgen Department of Pediatrics University of Minnesota Medical CenterMinneapolisMNUSA

Introduction The podocyte of the kidney plays a crucial role in both the structure and function of the normal glomeru- lus. With glomerular disease podocytes may change shape or become detached from the glomerular basement membrane. Podocytes have been found in urine of patients with glomerulosclerosis and other kidney diseases. There are reports that podocytes do not divide after the capillary loop stage of glomerular development, although other studies report podo- cyte hyperplasia during glomerular growth and hyper- plasia has been reported with some glomerular disea-

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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 spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： john mitrofanis Jonathan Stone michael R.Hamblin Pierre magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Human-tiger conflict:A review and call for comprehensive plans

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Integrative Zoology 2010年第4期5卷 300-312页

作者： john m.GOODRICH Wildlife Conservation Society BronxNew YorkNYUSA

Human-tiger(Panthera tigris Linnaeus,1758)conflicts(HTC),manifested primarily as attacks on people and domestic animals,exacerbate at least 2 major threats to tigers:(i)conflicts often result in mortality or removal of tigers from the wild;and(ii)they result in negative attitudes towards tigers by local people,thereby reducing support for tiger *** HTC has decreased over the past century,it will likely increase if current and proposed conservation initiatives to double tiger populations are *** HTC could undermine successful conservation initiatives if proactive steps are not taken to reduce *** present paper provides a review of the impacts of HTC and the measures taken to reduce it in ways that reduce negative impacts on both humans and tigers,and stresses the need for development and implementation of comprehensive plans to reduce HTC.

关键词： carnivore depredation human-tiger conflict Panthera tigris tiger

Fusion of bone marrow-derived cells with cancer cells: metastasis as a secondary disease in cancer

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Chinese Journal of Cancer 2014年第3期33卷 133-139页

作者： john m.Pawelek Department of Dermatology and the Yale Cancer Center Yale University School of Medicine

This perspective article highlights the leukocyte-cancer cell hybrid theory as a mechanism for cancer metastasis. Beginning from the first proposal of the theory more than a century ago and continuing today with the first proof for this theory in a human cancer, the hybrid theory offers a unifying explanation for metastasis. In this scenario, leukocyte fusion with a cancer cell is a secondary disease superimposed upon the early tumor, giving birth to a new, malignant cell with a leukocyte-cancer cell hybrid epigenome.

关键词： Bone marrow-derived cell-cancer cell hybrids metastasis cell fusion

Synthesis of LiSm_(0.01)mn_(1.99)O_4 by molten salt technique

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Journal of Rare Earths 2010年第2期28卷 255-259页

作者： m Helan L john Berchmans Department of Chemistry Jamal Mohamed College (Autonomous) Electropyrometallurgy Division Central Electrochemical Research Institute

Samarium substituted lithium manganese oxide powders were successfully prepared by molten-salt synthesis(mSS) using eutectic mixture of LiCl,SmCl3.6H2O and mnO2 salt at 700 °*** synthesis was carried out in open *** crystalline powders were characterized for their phase identification using X-ray diffraction(XRD) *** physico-chemical properties of the samarium substituted lithium manganese oxide powders were investigated by thermal analysis(TGA/DTA),FT-IR spectroscopy,EDAX,electron par...

关键词： LiSm0.01mn1.99O4 molten salt synthesis cathode materials rare earth ion

Fuzzy modeling of Surficial Uranium Prospectivity in British Columbia(Canada)with a Weighted Fuzzy Algebraic Sum Operator

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Journal of Earth Science 2021年第2期32卷 293-309页

作者： Emmanuel john m.Carranza School of Agricultural Earth and Environmental SciencesUniversity of KwaZulu-NatalWestville CampusDurban 4041South Africa

This paper demonstrates knowledge-guided fuzzy logic modeling of regional-scale surficial uranium(U)prospectivity in British Columbia(Canada).The deposits/occurrences of surficial U in this region vary from those in Western Australia and Namibia;thus,requiring innovative and carefully-thought techniques of spatial evidence generation and *** novelty,this papers introduces a new weighted fuzzy algebraic sum operator to combine certain spatial evidence *** analysis trialed several layers of spatial evidence based on conceptual mineral system model of surficial U in British Columbia(Canada)as well as tested various models of evidence ***-linear weighted functions of(a)spatial closeness to U-enriched felsic igneous rocks was employed as U-source spatial evidence,(b)spatial closeness to paleochannels as fluid pathways spatial evidence,and(c)surface water U content as chemical trap spatial *** best models of prospectivity created by integrating the layers of spatial evidence for U-source,pathways and traps predicted at least 85%of the known surficial U deposits/occurrences in>10%of the study region with the highest prospectivity fuzzy *** results of analyses demonstrate that,employing the known deposits/occurrences of surficial U for scrutinizing the spatial evidence layers and the final models of prospectivity can pinpoint the most suitable critical processes and models of data integration to reduce bias in the analysis of mineral prospectivity.

关键词： fuzzy logic mineral systems surficial uranium fuzzy algebraic sum

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Sorption and phase distribution of ethanol and butanol blended gasoline vapours in the vadose zone after release

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Journal of Environmental Sciences 2014年第3期26卷 608-616页

作者： Ejikeme Ugwoha john m. Andresen Chemical and Environmental Engineering University of Nottingham School of Engineering and Physical Sciences Heriot-Watt University

The sorption and phase distribution of 20% ethanol and butanol blended gasoline （E20 and B20） vapours have been examined in soils with varying soil organic matter （SOm） and water contents via laboratory microcosm experiments. The presence of 20% alcohol reduced the sorption of gasoline compounds by soil as well as the mass distribution of the compounds to soil solids. This effect was greater for ethanol than butanol. Compared with the sorption coefficient （Kd） of unblended gasoline compounds, the Kd of E20 gasoline compounds decreased by 54% for pentane, 54% for methylcyclopentane （mCP） and 63% for benzene, while the Kd of B20 gasoline compounds decreased by 39% for pentane, 38% for mCP and 49% for benzene, The retardation factor （R） of E20 gasoline compounds decreased by 53% for pentane, 53% for mCP and 48% for benzene, while the R of B20 gasoline compounds decreased by 39% for pentane, 37% for mCP and 38% for benzene. For all SOm and water contents tested, the Kd and R of all gasoline compounds were in the order of unblended gasoline 〉 B20 〉 E20, indicating that the use of high ethanol volume in gasoline to combat climate change could put the groundwater at greater risk of contamination,

关键词： butanol-blended gasoline ethanol-blended gasoline phase distribution soil organic matter soil water content sorption vadose zone

Host RNA circles and the origin of hepatitis delta virus

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World Journal of Gastroenterology 2014年第11期20卷 2971-2978页

作者： john m Taylor Fox Chase Cancer Center PhiladelphiaPA 19111United States

Recent reports show that many cellular RNAs are processed to form circular species that are relatively abundant and resistant to host *** some cases,such circles actually bind host *** depletion of available microRNAs appears to have biological roles;for instance,in homeostasis and *** findings regarding host RNA circles support a speculative reappraisal of the origin and mode of replication of hepatitis delta virus,hepatitis delta virus(HDV),an agent with a small circular RNA genome;specifically,it is proposed that in hepatocytes infected with hepatitis B virus(HBV),some viral RNA species are processed to circular forms,which by a series of chance events lead to an RNA that can be both replicated by host enzymes and assembled,using HBV envelope proteins,to form particles some of which are *** a model also may provide some new insights into the potential pathogenic potential of HDV *** return,new insights into HDV might provide information leading to a better understanding of the roles of the host RNA circles.

关键词： Hepatitis B virus Hepatitis delta virus Circular RNA Ribozymes microRNA