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Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-βinduced retinal pigmented epithelium degeneration

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1526-1534页

作者： Siddharth Narendran Felipe Pereira Praveen Yerramothu Ivana Apicella Shao-bin Wang Kameshwari Ambati Shuichiro Hirahara Younghee Kim Meenakshi Ambati Vidya l.Ambati Peirong Huang Akhil Varshney Yosuke Nagasaka Shinichi Fukuda kirstie l.baker Kenneth M.Marion Jan M.Deussing Srinivas R.Sadda Bradley D.Gelfand Jayakrishna Ambati Center for Advanced Vision Science University of Virginia School of MedicineCharlottesvilleVAUSA Department of Ophthalmology University of Virginia School of MedicineCharlottesvilleVAUSA Aravind Eye Care System MaduraiIndia Departamento de Oftalmologia e Ciências Visuais Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil Center for Digital Image Evaluation CharlottesvilleVAUSA Doheny Eye Institute Los AngelesLos AngelesCAUSA Molecular Neurogenetics Department of Stress Neurobiology and NeurogeneticsMax Planck Institute of PsychiatryMunichGermany Department of Ophthalmology David Geffen School of MedicineUniversity of California–Los AngelesLos AngelesCAUSA Department of Biomedical Engineering University of Virginia School of MedicineCharlottesvilleVAUSA Department of Pathology University of Virginia School of MedicineCharlottesvilleVAUSA Department of Microbiology Immunologyand Cancer BiologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA

Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global *** report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMD that is currently *** demonstrate that AβOs induce activation of the NlRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NlRP3 inflammasome activation,is required for AβO-induced RPE *** classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE *** findings crystallize the importance of P2RX7 and NlRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.

关键词： degeneration activation upstream

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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany M.Zúñiga Forrest l.baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of Medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos Santos P.J.Dijkstra C.Mota J.Bauer H.Ferreira Rui l.Reis N.Neves S.Camarero-Espinosa M.B.baker l.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate laboratory 4806-909 Braga/GuimarãesPortugal POlYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCl5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCl75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCl *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending Surface functionalization Surface density Click chemistry Human

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Stand dynamics of old-growth hemlock forests in central Bhutan are shaped by natural disturbances

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Forest Ecosystems 2024年第4期11卷 434-447页

作者： Karma Tenzin Craig R.Nitschke Kathryn J.Allen Raphael Trouve Thiet V.Nguyen Patrick J.baker School of Agriculture Foodand Ecosystem SciencesUniversity of Melbourne500 Yarra BlvdRichmondVictoriaAustralia School of Geography Planningand Spatial SciencesUniversity of TasmaniaSandy BayTasmaniaAustralia Forest Science Institute of South Vietnam 1 Pham Van Hai StreetTan Binh DistrictHo Chi Minh CityViet Nam

Understanding how past disturbances have influenced the development of forests is critical for deciphering their current structure and composition and forecasting future *** this study,dendrochronological methods were applied to uncover the disturbance history of old-growth hemlock-dominated forests in central *** of tree-ring samples from two old-growth hemlock stands,located in two different topographic settings,identified the importance of gap-phase dynamics in facilitating recruitment and growth releases and producing complex,multi-aged structure s over *** site showed evidence of a near stand-replacing disturbance in the late 1700s,while the other showed no evide nce of high-severity disturbance at any time over the last 400 *** both sites low-to medium-severity disturbances,some of which appear to be associated with cyclones originating in the Bay of Bengal,dominated the disturbance *** hemlock stands exhibited a significant positive association between cyclone occurrence and growth release events and between recruitment pulses and growth release *** 1800 to 1970 there was an increase in recruitment of angiosperm tree species at most sites and a corresponding decline in conifer *** the past 50 years there has been little new recruitment;this may be due to light limitation in the understory from shade-tolerant angiosperms and bamboo in the lower strata of these *** variations in disturbance dynamics and recruitment were observed across the study sites,suggesting that other factors,such as topography and climate,may be influencing long-term stand development *** study highlights the complex interplay between historical disturbance regimes and tree recruitment in shaping the age and size structures of old-growth hemlock forests in central *** also provides new insights into the dynamics of these forests that can be used to support effective forest conservation and management i

关键词： Forest structure Hemlock forest Himalaya Natural disturbance

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In Memoriam:*** ***

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International Soil and Water Conservation Research 2021年第4期9卷 485-489页

作者： Dennis C.Flanagan Richard M.Cruse James l.baker Paige Chyu USDA-Agricultural Research Service National Soil Erosion Research LaboratoryWest LafayetteINUSA Department of Agronomy Iowa State UniversityAmesIAUSA Department of Agricultural&Biosystems Engineering Iowa State UniversityAmesIAUSA International Research and Training Center on Erosion and Sedimentation BeijingChina

The soil erosion research and soil and water conservation global community lost a treasured member on November 20,2020,when *** Matthew laflen(Fig.1)*** one with a friendly welcoming smile,John had hundreds of friends,both personally and professionally throughout the *** article includes many of his professional and scientific contributions,and impacts from his research and outreach activities.

关键词： soil hundreds professional

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Dairy cows inoculated with highly pathogenic avian influenza virus H5N1

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四川生理科学杂志 2024年第10期46卷 2275-2275页

作者： Amy l.baker Virus and Prion Research Unit National Animal Disease Center Agricultural Research Service United States Department of Agriculture Ames Iowa USA National Veterinary Services laboratories Animal and Plant Health Inspection Service United States Department of Agriculture Ames Iowa USA Veterinary Diagnostic and Production Animal Medicine Iowa State University Ames Iowa USA

Highly pathogenic avian influenza(HPAI)H5N1 hemagglutinin clade 2.***.4.4b was detected in the United States in *** HPAI viruses caused mortality events in poultry,wild birds,and wild *** March 25,2024,HPAI H5N1 clade 2.***.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive herds were identified in 14 *** case description included reduced feed intake and rumen motility in lactating cows,decreased milk production,and thick yellow milk.2,3 The diagnostic investigation revealed viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium.A single transmission event,likely from birds,was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.***.4.4b genotype B3.13.4 We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating *** were inoculated by aerosol respiratory route and cows by intramammary *** disease was mild in heifers,but infection was confirmed by virus detection,lesions,and *** disease in lactating cows included decreased rumen motility,changes to milk appearance,and production *** was confirmed by high levels of viral RNA detected in milk,virus isolation,lesions in mammary tissue,and *** study provides the foundation to investigate additional routes of infection,pathogenesis,transmission,and intervention strategies.

关键词： H5N1 cows fir

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Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway

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Plant Communications 2024年第8期5卷 172-188页

作者： Hu-Jiao lan Jie Ran Wen-Xu Wang lei Zhang Ni-Ni Wu Ya-Ting Zhao Min-Jun Huang Min Ni Fen liu Ninghui Cheng Paul A.Nakata Jianwei Pan Steven A.Whitham Barbara J.baker Jian-Zhong liu Zhejiang Provincial Key laboratory of Biotechnology on Specialty Economic Plants Zhejiang Normal UniversityJinhua 321004China Institute of Plant Genetics and Developmental Biology College of Chemistry and Life SciencesZhejiang Normal UniversityJinhua 321004China College of life Sciences Lanzhou UniversityLanzhou 730000China Department of Plant Pathology and Microbiology Iowa State UniversityAmesIA 50011USA Department of Plant and Microbial Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA Plant Gene Expression Center U.S.Department of Agriculture-Agricultural Research ServiceAlbanyCA 94706USA lushan Botanical Garden Chinese Academy of SciencesJiujiang 332000China U.S.Department of Agriculture-Agricultural Research Service Children’s Nutrition Research CenterDepartment of PediatricsBaylor College of MedicineHoustonTX 77030USA

The crosstalk between clathrin-mediated endocytosis(CME)and the autophagy pathway has been reported in mammals;however,the interconnection of CME with autophagy has not been established in ***,we report that the Arabidopsis ClATHRIN lIGHT CHAIN(ClC)subunit 2 and 3 double mutant,clc2-1 clc3-1,phenocopies Arabidopsis AUTOPHAGY-RElATED GENE(ATG)mutants in both autoimmunity and nutrient ***,the autophagy pathway is significantly compromised in the clc2-1 clc3-1 ***,multiple assays demonstrate that ClC2 directly interacts with ATG8h/ATG8i in a domain-specific *** expected,both GFP-ATG8h/GFP-ATG8i and ClC2-GFP are subjected to autophagic degradation,and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 ***,simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum,supporting the functional relevance of the ClC2-ATG8h/8i *** conclusion,our results reveal a link between the function of ClCs and the autophagy pathway in Arabidopsis.

关键词： autophagy clathrin light chain immunity clathrin-mediated endocytosis senescence cell death

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The role of phosphorus in the metabolism of arsenate by a freshwater green alga, Chlorella vulgaris

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Journal of Environmental Sciences 2016年第11期28卷 169-178页

作者： Josh baker Dirk Wallschlager Trent University Environmental and Life Sciences Graduate Program 1600 West Bank Dr Peterborough ON K9L 0G2 Canada School of the Environment Department of Chemistry and Water Quality Centre Trent University 1600 West Bank Dr Peterborough ONK9L 0G2 Canada

A freshwater microalga, Chlorella vulgaris, was grown in the presence of varying phosphate concentrations（〈 10–500 μg/l P） and environmentally realistic concentrations of arsenate（As（Ⅴ））（5–50 μg/l As）. Arsenic speciation in the culture medium and total cellular arsenic were measured using AEC-ICP-MS and ICP-DRC-MS, respectively, to determine arsenic biotransformation and uptake in the various phosphorus scenarios. At high phosphate concentration in the culture medium, 〉 100 μg/l P, the uptake and biotransformation of As（Ⅴ） was minimal and dimethylarsonate（DMAs（Ⅴ）） was the dominant metabolite excreted by C. vulgaris, albeit at relatively low concentrations. At common environmental P concentrations, 0–50 μg/l P, the uptake and biotransformation of As（Ⅴ） increased. At these higher As-uptake levels, arsenite（As（Ⅲ）） was the predominant metabolite excreted from the cell. The concentrations of As（Ⅲ） in these low P conditions were much higher than the concentrations of methylated arsenicals observed at the various P concentrations studied. The switchover threshold between the（small） methylation and（large） reduction of As（Ⅴ） occurred around a cellular As concentration of 1 fg/cell. The observed nearly quantitative conversion of As（Ⅴ） to As（Ⅲ） under low phosphate conditions indicates the importance of As（Ⅴ） bio-reduction at common freshwater P concentrations. These findings on the influence of phosphorus on arsenic uptake, accumulation and excretion are discussed in relation to previously published research. The impact that the two scenarios of As（Ⅴ） metabolism, As（Ⅲ） excretion at high As（Ⅴ）-uptake and methylarsenical excretion at low As（Ⅴ）-uptake, have on freshwater arsenic speciation is discussed.

关键词： Arsenic Speciation Phosphorus Freshwater algae Toxicity Biotransformation

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Measuring and Visualizing Research Collaboration and Productivity

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Journal of Data and Information Science 2018年第1期3卷 54-74页

作者： Jon Garner Alan l.Porter Andreas leidolf Michelle baker Search Technology Inc. School of Public Policy Georgia Institute of Technology Ecology Center Utah State University Department of Biology Utah State University

Purpose： This paper presents findings of a quasi-experimental assessment to gauge the research productivity and degree of interdisciplinarity of research center outputs. Of special interest, we share an enriched visualization of research co-authoring patterns. Design/methodology/approach： We compile publications by 45 researchers in each of 1） the iUTAH project, which we consider here to be analogous to a ＂research center,＂ 2） CG1-a comparison group of participants in two other Utah environmental research centers, and 3） CG2--a comparison group of Utah university environmental researchers not associated with a research center. We draw bibliometric data from Web of Science and from Google Scholar. We gather publications for a period before iUTAH had been established （2010-2012） and a period after （2014-2016）. We compare these research outputs in terms of publications and citations thereto. We also measure interdisciplinarity using Integration scoring and generate science overlay maps to locate the research publications across disciplines. Findings： We find that participation in the iUTAH project appears to increase research outputs （publications in the After period） and increase research citation rates relative to the comparison group researchers （although CG 1 research remains most cited, as it was in the Before period）. Most notably, participation in iUTAH markedly increases co-authoring among researchers--in general; and for junior, as well as senior, faculty; for men and women： across organizations; and across disciplines. Research limitations： The quasi-experimental design necessarily generates suggestive, not definitively causal, findings because of the imperfect controls. Practical implications： This study demonstrates a viable approach for research assessment of a center or program for which random assignment of control groups is not possible. It illustrates use of bibliometric indicators to inform R＆D program management. Originality/value： New visualizations

关键词： Bibliometrics Interdisciplinarity Multidisciplinarity Research evaluation Research collaboration mapping Science visualization Scientometrics Social networkanalysis

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Comparison of Phosphorus Sorption by light-Weight Aggregates Produced in the United States

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Pedosphere 2014年第6期24卷 808-816页

作者： M.D.baker S.SIMKINS l.A.SPOKAS P.l.M.VENEMAN B.S.XING Stockbridge School of Agriculture University of MassachusettsAmherstMA 01003 (USA) U.S.Army Fort HoodTX 76544 (USA)

In this study, phosphorus(P) sorption of thirteen light-weight aggregates(lWAs) from USA was compared during batch equilibrium experiments in order to identify those materials which had the highest P sorption capacity for further study. Seven different levels of sorption activity were observed, which were broadly grouped into three categories—high performing, middle performing, and low performing aggregates. Chemical analysis of Ca, Al, Fe, and Mg was used to describe the differences between lWAs. There was a significant correlation between cation(especially Al, Ca, Fe, and Mg) content and P sorbed. langmuir isotherms were used to describe P sorption maximum and binding affinity for four of the top five performing lWAs, Universal, Stalite "D", Stalite "Mix", and *** fifth aggregate, lehigh, exhibited more complex sorption, and was better described by the Freundlich isotherm. Universal had a mean P sorption at the highest concentration of 824 mg kg-1, well above its calculated sorption maximum(702 mg kg-1), and also had the highest binding affinity(1.1 l mg-1). This experiment suggests that the top performing lWA(Universal) may perform poorly in column and field studies due to observed precipitates, which could degrade constructed wetland performance. Other lWAs may exhibit superior field performance due to their high calculated sorption maxima. In general, these results highlight the importance of batch experiments as a first step in identifying materials suitable for column and field experiments.

关键词： binding affinity constructed wetlands equilibrium P concentration media P sorption capacity

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