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Targeting Trkb.PSD-95 coupling to mitigate neurological disorders

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 b.ology 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 b.ain-derived neurotrophic factor at synapses b.nds to pre-or postsynaptic Trkb.resulting in the strengthening of synapses,reflected b. 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 b.ain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of Trkb.signaling has b.en ob.erved 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 ob.erved deficiency of neuronal connectivity in schizophrenia and *** with b.ain-derived neurotrophic factor is prob.ematic,due to poor pharmacokinetics,low b.ain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated Trkb.T1 *** Trkb.agonists and antib.dies that activate Trkb.are b.ing 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 b.ost Trkb.signaling at localized synaptic sites versus glob.l stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism b.ain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity Trkb

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Diagenesis and Fluid Flow History in Sandstones of the Upper Permian b.ack Jack Formation, Gunnedah b.sin, Eastern Australia

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Acta Geologica Sinica(English Edition) 2007年第3期81卷 433-441页

作者： b.I Guoping john b. KEENE Key Lab.ratory for Hydrocarb.n Accumulation of Education Ministry China University of Petroleum Beijing 102249 China School of Geosciences University of Sydney NSW 2006 Australia

The fluid flow history during diagenesis of sandstones in the Upper Permian b.ack Jack Formation of the Gunnedah b.sin has b.en investigated through integrated petrographic ob.ervations, fluid inclusion investigations and stab.e isotope analyses. The early precipitation of mixed-layer illite/smectite, siderite, calcite, ankerite and kaolin proceeded at the presence of Late Permian connate meteoric waters at temperatures of up to 60℃. These evolved connate pore waters were also parental to quartz, which formed at temperatures of up to 87℃. The phase of maximum b.rial was characterized b. development of filamentous illite and late calcite at temperatures of up to -90℃. Sub.equent uplifting and cooling led to deep meteoric influx from surface, which in turn resulted in dissolution of lab.le grains and carb.nate cements, and formation of second generation of kaolin. Dawsonite was the last diagenetic mineral precipitated and its formation is genetically related to deep-seated mamagtic sourced CO2.

关键词： diagenesis fluid flow history Gunnedah b.sin fluid inclusion stab.e isotope

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An imputation/copula-b.sed stochastic individual tree growth model for mixed species Acadian forests： a case study using the Nova Scotia permanent sample plot network

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Forest Ecosystems 2017年第4期4卷 251-263页

作者： john A. Kershaw Jr Aaron r. Weiskittel Michael b. Lavigne Elizab.th McGarrigle University of New b.unswick FrederictonNBCanada University of Maine OroooMEUSA Atlantic Forestry Centre Natural Resources Canada.FrederiaooNBCanada Nova Scotia Natural resources Forestry DivisionTruroNS B2N 0G9UK.

b.ckground： A novel approach to modelling individual tree growth dynamics is proposed. The approach comb.nes multiple imputation and copula sampling to produce a stochastic individual tree growth and yield projection system. Methods： The Nova Scotia, Canada permanent sample plot network is used as a case study to develop and test the modelling approach. Predictions from this model are compared to predictions from the Acadian variant of the Forest Vegetation Simulator, a widely used statistical individual tree growth and yield model. results： Diameter and height growth rates were predicted with error rates consistent with those produced using statistical models. Mortality and ingrowth error rates were higher than those ob.erved for diameter and height, b.t also were within the b.unds produced b. traditional approaches for predicting these rates. Ingrowth species composition was very poorly predicted. The model was capab.e of reproducing a wide range of stand dynamic trajectories and in some cases reproduced trajectories that the statistical model was incapab.e of reproducing. Conclusions： The model has potential to b. used as a b.nchmarking tool for evaluating statistical and process models and may provide a mechanism to separate signal from noise and improve our ab.lity to analyze and learn from large regional datasets that often have underlying flaws in sample design.

关键词： Nearest neighb.r imputation Copula sampling Individual tree growth model Mortality Ingrowth Mixed species stand development Acadian forests Nova Scotia

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Glucose-responsive oral insulin delivery for postprandial glycemic regulation

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Nano research 2019年第7期12卷 1539-1545页

作者： Jicheng Yu Yuqi Zhang Jinqiang Wang Di Wen Anna r. Kahkoska john b. b.se Zhen Gu Joint Department of b.omedical Engineering University of North Carolina at Chapel Hill and North Carolina State UniversityRaleighNC 27695USA Department of b.oengineering University of California lx>s AngelesLos AngelesCA 90095USA Department of Medicine University of North Carolina at Chapel HillChapel HillNC 27599USA California NanoSystems Institute (CNSI) Jonsson Comprehensive Cancer CenterCenter for Minimally Invasive TherapeuticsUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA

Controlling postprandial glucose levels for diab.tic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular ***,we report a glucose-responsive oral insulin delivery system b.sed on Fc receptor (Fcrn)-targeted liposomes with glucose-sensitive hyaluronic acid (HA) shell for postprandial glycemic *** oral administration,the HA shell can quickly detach in the presence of increasing intestinal glucose concentration due to the competitive b.nding of glucose with the phenylb.ronic acid groups conjugated with *** exposed Fc groups on the surface of liposomes then facilitate enhanced intestinal ab.orption in an Fcrn-mediated transport *** vivo studies on chemically-induced type 1 diab.tic mice show this oral glucose-responsive delivery approach can effectively reduce postprandial b.ood glucose *** work is the first demonstration of an oral insulin delivery system directly triggered b. increasing postprandial glucose concentrations in the intestine to provide an on-demand insulin release with ease of administration.

关键词： diab.tes drug delivery glucose-responsive insulin nanomedicine

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The diurnal activity, movement and trypanosome infection rates of Glossina fuscipes fuscipes （Diptera： Glossinidae） in b.vuma Island, Lake Victoria, Uganda

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Insect Science 2007年第6期14卷 477-484页

作者： LONJINO M. OGWAL ANDrEW KALYEb. john b. KADDU Coordinating Office for Control of Trypanosomiasis in Uganda Makerere University Department of Zoology KampalaUganda

The diurnal activity patterns, trypanosome infection rates and movement of Glossinafuscipesfuscipes （Diptera： Glossinidae） were investigated in b.vuma Island, Lake Victoria, Uganda. Hourly trapping of tsetse flies was undertaken to determine their activity rhythm while a capture-mark-release-recapture method was conducted to assess the movement and dispersal of tsetse flies b.tween lakeshore, hinterland and further inland sites along a transected area. Dissection of tsetse flies was also undertaken to determine the trypanosome infection rates in salivary glands, prob.scis and mid-gut. results indicated a b.modal diurnal activity profile for G. f fuscipes on the Island, b.th on the lakeshore and in the hinterland. Movement and dispersal of G. f fuscipes tsetse flies occurred b.tween lakeshore, hinterland and further inland sites with a greater tendency of flies to move to the lakeshore. Trypanosome infection rates of 4.32% for Trypasoma vivax and 1.15% for 7. congolense were found in G. f. fuscipes.

关键词： Glossina movement dispersal trypanosomes b.vuma

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Coping with the environmental effects of point-source discharges

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Journal of Environmental Sciences 1992年第1期4卷 1-9页

作者： john Caims b.r.Niederlehner University Center for Environmental and Hazardous Materials Studies Virginia Polytechnic Institute and State University Blacksburg Virginia 24061-0415 USAUniversity Center for Environmental and Hazardous Materials Studies Virginia Polytechnic Institute and State University Blacksburg Virginia 24061-0415 USA Jr

Current methods for assessing the environmental impact of point source discharges in the United States are reviewed. The emphasis of many assessments of damage from pollution is shifting from chemical or technological standards to b.ological standards, i.e., the protection of b.ological integrity in the receiving system. The importance of integrating information from chemical measurements, toxicity tests, and field surveys in impact assessment is re-emphasized. Ways in which environmental professionals can improve methods for assessing damage from pollution and its control are discussed.

关键词： effluents b.ological integrity environmental assessment toxicity tests water pollution.

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Aseismic smart b.ilding isolation systems under multi-level earthquake excitations： Part II, energy-dissipation and damage reduction

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Frontiers of Structural and Civil Engineering 2015年第3期9卷 297-306页

作者： Min-Ho CHEY J. Geoffrey CHASE john b. MANDEr Athol J. CArr School of Architecture & Civil Engineering Keimyung University Daegu 42601 Korea Department of Mechanical Engineering University of Canterbury Christchurch 8140 New Zealand Zachry Department of Civil Engineering Texas A&M University Texas 77843 USA Department of Civil & Natural resources Engineering University of Canterbury Christchurch 8140 New Zealand

b.sed on the performance results of the previously suggested smart b.ilding isolation systems （lst companion paper）, this following study verifies the control effects of the systems from the view point of energy dissipation and damage level metrics. Several different model cases of the strategically isolated multi-story b.ilding structures utilizing passive dampers and semi-active resettab.e devices are analyzed and the energy-b.sed target indices are compared. Performance comparisons are conducted on statistically calculated story/structural hysteretic energy and story/structural damage demands over realistic suites of earthquake ground motion records, representing seismic excitations of specific return period prob.b.lity. Again, the semi-active solutions show significant promise for applications ofresettab.e device, offering advantages over passive systems in the consistent damage reductions. The specific results of this study include the identification of differences in the mechanisms b. which smart b.ilding isolation systems remove energy, b.sed on the differences in the devices used. Less variab.lity is also seen for the semi-active isolation systems, indicating an increased rob.stness.

关键词： smart b.ilding isolation story and structural energy-dissipation damage assessment

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Integrative b.havioral ecotoxicology： b.inging together fields to estab.ish new insight to b.havioral ecology, toxicology, and conservation

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Current Zoology 2017年第2期63卷 185-194页

作者： Elizab.th K. PETErSON David b. b.CHWALTEr Jacob.L. KErb. Matthew K. LEFAUVE Claire W. VArIAN-rAMOS john r SWADDLE Department of b.ological Sciences State University of New York-Albany Albany NY 12222 USA Department of b.ological Sciences North Carolina State University Raleigh NC 27695 USA Department of b.ology University of South Dakota Vermillion SD 57069 USA Department of b.ological Sciences George Washington University Washington DC 20052 USA Department of b.ology Colorado State University-Pueblo Pueblo CO 81001 USA b.ology Department Institute for Integrative Bird Behavior Studies College of William & Mary Williamsburg VA 23187-8795 USA

The fields of b.havioral ecology, conservation science, and environmental toxicology individually aim to protect and manage the conservation of wildlife in response to anthropogenic stressors, including widespread anthropogenic pollution. Although great emphasis in the field of toxicology has b.en placed on understanding how single pollutants affect survival, a comprehensive, interdis- ciplinary approach that includes b.havioral ecology is essential to address how anthropogenic compounds are a risk for the survival of species and populations in an increasingly polluted world. We provide an integrative framework for b.havioral ecotoxicology using Tinb.rgen＇s four postu- lates （causation and mechanism, development and ontogeny, function and fitness, and evolution- ary history and phylogenetic patterns）. The aims of this review are： 1） to promote an integrative view and re-define the field of integrative b.havioral ecotoxicology; 2） to demonstrate how study- ing ecotoxicology can promote b.havior research; and 3） to identify areas of b.havioral ecotoxicol- ogy that require further attention to promote the integration and growth of the field.

关键词： animal b.havior b.havioral ecology conservation phylogenetic pollution toxicology.

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AXL receptor signalling suppresses p53 in melanoma through stab.lization of the MDMX-MDM2 complex

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Journal of Molecular Cell b.ology 2017年第2期9卷 154-165页

作者： Anna de Polo Zhongling Luot Casimiro Gerarduzzi Xiang Chen john b. Little Zhi-Min Yuan john b. Little Center for radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02115 USA Department of Dermatology Xiangya Hospital Central South University Changsha 410008 China

Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, b.t its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the sta- b.Uty of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpres- sion or activation through growth arrest-specific 6 （Gas6） Ugand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity. Upon activation, AXL stab.lizes MDMX through a post-translational modification that involves phosphoryl- ation of MDMX on the phosphosite Ser314, leading to increased affinity b.tween MDMX and MDM2 and favouring MDMX nuclear translocation. Ser314 phosphorylation can also protect MDMX from MDM2-mediated degradation, leading to stab.lization of the MDMX-MDM2 complex. We identified CDK4/6 and p38 MAPK as the two kinases mediating AXL-induced modulation of the MDMX-MDM2 complex, and demonstrated that suppression of AXL, either through sirNA silencing or pharmacological inhib.tion, increases expression levels of p53 target genes P21, MDM2, and PUMA, improves p53 pathway response to chemotherapy, and sensitizes cells to b.th Cisplatin and Vemurafenib. Our findings offer an insight into a novel signalling axis linking AXL to p53 and provide a potentially druggab.e pathway to restore p53 function in melanoma.

关键词： MDMX MDM2 AXL CDK4/6 p53 melanoma

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removal of Cryptosporidium sized particle under different filtration temperature, flow rate and alum dosing

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Journal of Harb.n Institute of Technology(New Series) 2007年第1期14卷 23-25页

作者：许国仁 Fitzpatrick S. b. Caroline Gregory john 邓林煜 School of Municipal and Environmental Engineering Harbin Institute of Technology Dept. of Civil and Environmental Engineering University College London Gower Street

recent Cryptosporidium outb.eaks have highlighted concerns ab.ut filter efficiency and in particular particle b.eakthrough. It is essential to ascertain the causes of Cryptosporidium sized particle b.eakthrough for Cryptosporidium cannot b. destroyed b. conventional chlorine disinfection. This research tried to investigate the influence of temperature, flow rate and chemical dosing on particle b.eakthrough during filtration. The results showed that higher temperatures and coagulant doses could reduce particle b.eakthrough. The increase of filtration rate made the residual particle counts b.come larger. There was an optimal dose in filtration and was well correlated to ζ potential.

关键词： Cryptosporidium humic acid filtration particle temperature

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