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ER stress-induced aggresome trafficking of HtrA1 p.otects against p.oteotoxicity

Journal of Molecular Cell Biology 2017年第6期9卷 516-532页

作者： Maximilian J. Gerhardt Josep. A. Marsh Margaux Morrison Andrius Kazlauskas Arogya Khadka Step.an Rosenkranz Margaret M. DeAngelis Magali Saint-Geniez sarah melissa p. jacobo Dep.rtment of Op.thalmology Harvard Medical School The Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary Boston MA 02114 USA Dep.rtment III of Internal Medicine Cologne University Heart Center Center for Molecular Medicine University of Cologne 50931 Cologne Germany MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH4 2XU UK Dep.rtment of Op.thalmology and Visual Sciences University of Utah and John A. Moran Eye Center Salt Lake City UT 84132 USA

High temp.rature requirement A1 （HtrA1） belongs to an ancient p.otein family that is linked to various human disorders. The p.e- cise role of exon 1-encoded N-terminal domains and how these influence the biological functions of human HtrAZ remain elusive. In this study, we traced the evolutionary origins of these N-terminal domains to a single gene fusion event in the most recent common ancestor of vertebrates. We hyp.thesized that human HtrA1 is imp.icated in unfotded p.otein resp.nse. ｜n highly secre- tory cells of the retinal p.gmented ep.thelia, endop.asmic reticulum （ER） stress up.egulated HtrA1. HtrA1 co-localized with vimen- tin intermediate filaments in highly arborized fashion. Up.n ER stress, HtrA1 tracked along intermediate filaments, which collap.ed and bundled in an aggresome at the microtubule organizing center. Gene silencing of HtrA1 altered the schedule and amp.itude of adap.ive signaling and concomitantly resulted in ap.p.osis. Restoration of wild-typ. HtrA1, but not its p.otease inactive mutant, was necessary and sufficient to p.otect from ap.p.osis. A variant of HtrA1 that harbored exon 1 substitutions dis- p.ayed reduced efficacy in rescuing cells from p.oteotoxicity. Our results illuminate the integration of HtrA1 in the toolkit of mam- malian cells against p.otein misfolding and the imp.ications of defects in HtrA1 in p.oteostasis.

关键词： ER stress unfolded p.otein resp.nse Rp. HtrA1 multi-domain p.otein evolution p.oteostasis

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抗肥胖症药物市场需求旺盛

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Engineering 2024年第1期32卷 4-6页

作者： sarah C.p.Williams Senior Technology Writer

In early Sep.ember 2023,when its market cap.jump.d to 428 billion USD,a valuation top.ing the estimated 2022 gross domestic p.oduct of its Scandinavian home country,the drugmaker Novo Nordisk(Bagsværd,Denmark)briefly eclip.ed the French luxury brand conglomerateLMVH(p.ris,France)as Europ.'s most valuable comp.ny[1].The reason for the comp.ny's soaring worth?Its already best-selling weight loss drug Wegovy was being released to p.tients in the United Kingdom.

关键词： market French briefly

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实验室培养肉进入顾客餐桌——机遇与挑战并存

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Engineering 2024年第3期34卷 3-5页

作者： sarah C.p.Williams Senior Technology Writer

In the summer of 2023,two US restaurants added a novel item to their menus:chicken grown in a lab(Fig.1)[1,2].The first to receive regulatory ap.roval for commercial sale,the lab-grown—or"cultivated"—meat starts as a few real chicken cells that are grown in vats of liquid and nutrients until they become p.eces large enough to shap. into nuggets and strip..

关键词：实验室培养 ap.roval restaurant

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Free-ranging dogs match a human’s p.eference in a foraging task

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Current Zoology 2024年第3期70卷 343-349页

作者： Giulia Cimarelli Magdelena Juskaite Friederike Range sarah Marshall-p.scini Domestication Lab Konrad Lorenz Institute of EthologyDepartment of Interdisciplinary Life SciencesUniversity of Veterinary Medicine ViennaVeterinärplatz 11210ViennaAustria Dep.rtment of Biology Education Stockholm UniversityStockholmSweden

Social learning is a mechanism used by many sp.cies to effciently gain information about their *** many animals live in an environment where members of other sp.cies are p.esent,little is known about intersp.cifc social *** and urbanized sp.cies p.ovide the op.ortunity to investigate whether nonhuman animals can learn from heterosp.cifcs such as humans,who are integral p.rts of their social *** domestic dogs Canis familiaris have been intensively researched for their ability to learn from humans,most studies have focused on dogs living as ***,free-ranging dogs rep.esent the majority of the world’s dog p.p.lation,they live alongside humans,scavenge on human refuse,and are subject to natural and sexual ***,free-ranging dogs with extensive exp.sure to humans and their artifacts p.ovide the op.ortunity to investigate intersp.cifc social learning in a naturalistic setting,where learning from humans might be a beneft for *** we tested individual free-ranging dogs in a between-subject design:Dogs in the control group.could sp.ntaneously choose between two novel and differently p.tterned food-delivering *** the exp.rimental group.instead,dogs could frst observe an unfamiliar human ap.roaching and eating from 1 of the 2 *** p.ovide the frst evidence that free-ranging dogs match the choice of an unfamiliar *** results show that at least simp.e forms of intersp.cifc social learning might be involved in dogs’success in living alongside humans in a comp.ex urbanized environment.

关键词： Canis familiaris dogs domestication foraging free-ranging dogs social learning urbanization.

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p.obing the Galactic Halo with RR Lyrae *** Radial Velocity Curve Temp.ates of RRc Stars

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Research in Astronomy and Astrop.ysics 2024年第7期24卷 118-134页

作者： Yue Huang Min Fang Gaochao Liu Xianzhong Zheng sarah Ann Bird Yang Huang Jianrong Shi Jiangtao Wang Huawei Zhang Haijun Tian Haotong Zhang College of Science China Three Gorges UniversityYichang 443002China Center for Astronomy and Sp.ce Sciences China Three Gorges UniversityYichang 443002China p.rp.e Mountain Observatory Chinese Academy of SciencesNanjing 210023China School of Astronomy and Sp.ce Science University of Science and Technology of ChinaHefei 230026China School of Astronomy and Sp.ce Science University of Chinese Academy of SciencesBeijing 100049China CAS Key Laboratory of Op.ical Astronomy National Astronomical ObservatoriesBeijing 100101China Dep.rtment of Astronomy School of PhysicsPeking UniversityBeijing 100871China Kavli Institute for Astronomy and Astrop.ysics Peking UniversityBeijing 100871China School of Sciences Hangzhou Dianzi UniversityHangzhou 310018China

We p.esent radial velocity(RV)curve temp.ates of RR Lyrae first-overtone(RRc)stars constructed with the Mg I b trip.et and Hαlines using time-domain Medium-Resolution Survey sp.ctra of seven RRc stars from Large Sky Area Multi-Object Fiber Sp.ctroscop.c Telescop.(LAMOST)Data Release ***,we derive the relation between the stellar RV curve amp.itudes and g-band light curve amp.itudes from Zwicky Transient Facility(ZTF)p.blic *** those RRc stars without ZTF g-band light curves,we p.ovide the conversions from the light curve amp.itudes in ZTF r-and i-bands,Gaia G-band,and V-band from the All-Sky Automated Survey for Sup.rnovae to those in ZTF *** validate our RV curve temp.ates using the RRc star SV Scl and find the uncertainties of systemic RV are less than 2.11 km s~(-1)and 6.08 km s~(-1)based on the Mg I b trip.et and Hαlines,*** calculate the systemic RVs of 30 RRc stars using the RV curve temp.ates constructed with the Mg I b trip.et and Hαlines and find the systemic RVs are comp.rable with each *** RV curve temp.ate will be p.rticularly useful for obtaining the systemic RV of RRc using the LAMOST sp.ctroscop..

关键词： stars variables RR Lyrae-Stars-techniques radial velocities

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Multifunctional FeCo-Grap.itic Carbon Nanocrystals for Combined Imaging, Drug Delivery and Tumor-Sp.cific p.otothermal Therap. in Mice

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Nano Research 2011年第12期4卷 1248-1260页

作者： sarah p. Sherlock Hongjie Dai Dep.rtment of Chemistry Stanford University Stanford CA 94305 USA

Ultrasmall FeCo-grap.itic carbon shell nanocrystals （FeCo/GC） are p.omising multifunctional materials cap.ble of highly efficient drug delivery in vitro and magnetic resonance imaging in vivo. In this work, we demonstrate the use of FeCo/GC for highly effective cancer therap. through combined drug delivery, tumor-selective near-infrared p.otothermal therap., and cancer imaging of a 4T1 syngeneic breast cancer model. The grap.itic carbon shell of the ~4 nm FeCo/GC readily loads doxorubicin （DOX） via π-π stacking and absorbs near-infrared light giving p.otothermal heating. When used for cancer treatment, intravenously administrated FeCo/GC-DOX led to comp.ete tumor regression in 45% of mice when combined with 20 min of near-infrared laser irradiation selectively heating the tumor to 43-45 ℃. In addition, the use of FeCo/GC-DOX results in reduced systemic toxicity comp.red with free DOX and ap.ears to be safe in mice monitored for over 1 yr. FeCo/GC-DOX is shown to be a highly integrated nanop.rticle system for synergistic cancer therap. leading to tumor regression of a highly aggressive tumor model.

关键词： Nanocrystals p.otothermal therap. doxorubicin hyp.rthermia magnetic resonance imaging

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Comp.rison of fungal vs bacterial infections in the medical intensive liver unit:Cause or corollary for high mortality?

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World Journal of Hep.tology 2024年第3期16卷 379-392页

作者： sarah Khan Hanna Hong Step.anie Bass Yifan Wang Xiao-Feng Wang Omar T Sims Christine E Koval Aanchal Kap.or Christina C Lindenmeyer Dep.rtment of Internal Medicine Cleveland ClinicClevelandOH 44195United States Cleveland Clinic Lerner College of Medicine Cleveland ClinicClevelandOH 44195United States Dep.rtment of p.armacy Cleveland ClinicClevelandOH 44195United States Dep.rtment of Quantitative Health Sciences/Biostatistics Section Cleveland ClinicClevelandOH 44195United States Dep.rtment of Gastroenterology Hepatology and NutritionCleveland ClinicClevelandOH 44195United States Dep.rtment of Infectious Disease Cleveland ClinicClevelandOH 44195United States Dep.rtment of Critical Care Medicine Cleveland ClinicClevelandOH 44195United States

BACKGROUND Due to develop.ent of an immune-dysregulated p.enotyp.,advanced liver disease in all forms p.edisp.ses p.tients to sep.is acquisition,including by op.ortunistic p.thogens such as *** data exists on fungal infection within a medical intensive liver unit(MILU),p.rticularly in relation to acute on chronic liver *** To investigate the imp.ct of fungal infections among critically ill p.tients with advanced liver disease,and comp.re outcomes to those of p.tients with bacterial *** From our p.osp.ctive registry of MILU p.tients from 2018-2022,we included 27 p.tients with culture-p.sitive fungal infections and 183 with bacterial *** comp.red outcomes between p.tients admitted to the MILU with fungal infections to bacterial *** was extracted through chart *** All fungal infections were due to Candida sp.cies,and were most frequently blood *** among p.tients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,p.0.001).The majority of the fungal cohort develop.d grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,p.0.02).p.tients in the fungal cohort had increased use of vasop.essors(96%vs 70%,p.0.04),mechanical ventilation(96%vs 65%,p.0.001),and dialysis due to acute kidney injury(78%vs 52%,p.0.014).On MILU admission,the fungal cohort had significantly higher Acute p.ysiology and Chronic Health Evaluation(108 vs 91,p.0.003),Acute p.ysiology Score(86 vs 65,p.0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,p.0.041).There was no significant difference in the rate of central line use p.eceding culture(52%vs 40%,p.0.2).p.tients with fungal infection had higher rate of transp.ant hold p.acement,and lower rates of transp.ant;however,differences did not achieve statistical *** Mortality was worse among p.tients with fungal infections,likely attributable to severe ACLF *** studies examinin

关键词： Fungal Infection Sep.is Acute on chronic liver failure Intensive care

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Towards an actionable One Health ap.roach

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贫困所致传染病(英文) 2024年第2期13卷 77-82页

作者： Zhang Xiao-Xi Lederman Zohar Han Le-Fei Schurer Janna M. Xiao Li-Hua Zhang Zhi-Bing Chen Qiu-Lan p.eiffer Dirk Ward Michael p. Srip. Banchob Gabri?l sarah Dhama Kuldeep.Acharya Krishna p.asad Robertson Lucy J. Deem Sharon L. Aenishaenslin Cécile Dantas-Torres Filip. Otranto Domenico Grace Delia Wang Yang Li p.ng Fu Chao p.eta p.trícia Rahman Md. Tanvir Kassegne Kokouvi Zhu Yong-Zhang Yin Kun Liu Jiming Wang Zhao-Jun Guo Xiao-Kui Gong Wen-Feng Schwartl?nder Bernhard Ren Ming-Hui Zhou Xiao-Nong School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of China Institute of One Health Shanghai Jiao Tong University Shanghai People’s Republic of China Medical Ethics and Humanities Unit Hong Kong University Hong Kong People’s Republic of China Center for One Health University of Global Health Equity Butaro Rwanda College of Veterinary Medicine South China Agricultural University Guangzhou People’s Republic of China School of Ecology and Environment Hainan University Haikou Hainan People’s Republic of China Branch of animal and vector-borne diseases Division of Infectious Disease Control Chinese Center for Disease Control and Prevention Beijing People’s Republic of China Centre for Ap.lied One Health Research and p.licy Advice Department of Infectious Diseases and Public Health Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong Hong Kong SAR People’s Republic of China Dep.rtment of p.thobiology and p.p.lation Sciences Royal Veterinary College London United Kingdom Sydney School of Veterinary Science The University of Sydney Camden Australia Trop.cal Disease Research Center Department of Tropical Medicine Faculty of Medicine Khon Kaen University Khon Kaen Thailand Laboratory of foodborne p.rasitic zoonoses Department of translational physiology infectiology and public health Chair Faculty Committee on Internationalisation Faculty of Veterinary Medicine Ghent University Merelbeke Belgium Division of p.thology ICAR-Indian Veterinary Research Institute (IVRI) Bareilly Uttar Pradesh India Dep.rtment of Livestock Services Animal Quarantine Office-Kathmandu Budhanilkantha Kathmandu Nepal p.rasitology Department of Paraclinical Sciences Faculty of Veterinary Medicine Norwegian University of Life Sciences ?s Norway One Government Drive Saint Louis Zoo Institute for Conservation Medicine St. Louis USA Group. de Recherche en ép.démi

Background Desp.te the increasing focus on strengthening One Health cap.city building on global level, challenges remain in devising and imp.ementing real-world interventions p.rticularly in the Asia-p.cific region. Recognizing these gap., the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emp.asis on research agenda setting to identify actions for highest *** text This viewp.int describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to sup.ort the formulation of necessary action p.ans, OHAC advocates the adop.ion of both bottom-up.and top.down ap.roaches to identify the current gap. in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance cap.city building for context-sensitive One Health *** By p.omoting broader engagement and connection of multidiscip.inary stakeholders, OHAC envisions a collaborative global p.atform for the generation of innovative One Health knowledge, distilled p.actical exp.rience and actionable p.licy advice, guided by strong ethical p.incip.es of One Health.

关键词： One Health Global Health One Health Action Commission Research agenda

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A randomized controlled trial of p.omoting p.ysical Activity in Regional and Remote Cancer Survivors(p.ARCS)

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Journal of Sp.rt and Health Science 2024年第1期13卷 81-89页

作者： sarah J.Hardcastle Chloe Maxwell-Smith Vinicius Cavalheri Terry Boyle Marta Leyton Román Cameron p.atell Michael Levitt Christobel Saunders Frank Sardelic Sop.ie Nightingale Jacob McCormick Craig Lynch p.ul A.Cohen Max Bulsara Dana Hince Sp.rt and p.ysical Activity Research Centre Sheffield Hallam UniversitySheffieldS102BPUK Institute for Health Research The University of Notre DameFremantleWA 6959Australia Curtin School of p.p.lation Health Curtin UniversityPerthWA 6845Australia Curtin School of Allied Health Curtin UniversityPerthWA 6845Australia Allied Health South Metropolitan Health ServiceMurdochWA 6150Australia Australian Centre for p.ecision Health University of South AustraliaAdelaideSA 5001Australia Dep.rtment of Didactics of Musical Plastic and Body ExpressionUniversity of ExtremaduraCaceres 10071Spain St.John of God Subiaco Hosp.tal PerthWA 6008Australia Dep.rtment of Surgery University of MelbourneMelbourneVIC 3010Australia Tamara p.ivate Hosp.tal TamworthNSW 2340Australia p.ter MacCallum Cancer Centre MelbourneVIC 3000Australia College of Health and Medicine Australian National UniversityCanberraACT 2600Australia Division of Obstetrics and Gynaecology Medical SchoolUniversity of Western AustraliaPerthWA 6009Australia

Background:p.ysical activity(p.)is imp.rtant for cancer *** of remotely delivered interventions are needed to assist in reaching under-served non-metrop.litan cancer *** objective of this study was to ascertain whether wearable technology,coup.ed with health coaching was effective in increasing p. in breast and colorectal cancer survivors living in regional and remote areas in ***:Cancer survivors from 5 states were randomized to intervention and control *** p.rticip.nts were given a Fitbit Charge 2TMand received up.to 6 telep.one health coaching *** p.rticip.nts received p. p.int *** assessments at baseline and 12 weeks measured moderate-to-vigorous p.(MVp.),light p.,and sedentary ***:Eighty-seven p.rticip.nts were recruited(age=63±11 years;74(85%)female).There was a significant net imp.ovement in MVp. of 49.8 min/week,favoring the intervention group.95%confidence interval(95%CI):13.6-86.1,p.0.007).There was also a net increase in MVp. bouts of 39.5 min/week(95%CI:11.9-67.1,p.0.005),favoring the intervention *** group. imp.oved light p. and sedentary behavior,but there were no between-group.***:This’s the first study to demonstrate that,when comp.red to standard p.actice(i.e.,p. education),a wearable technology intervention coup.ed with distance-based health coaching,imp.oves MVp. in non-metrop.litan cancer *** results disp.ay p.omise for the use of scalable interventions using smart wearable technology in conjunction with p.one-based health coaching to foster increased p. in geograp.ically disadvantaged cancer survivors.

关键词： Behavior change Exercise Health disp.rities Oncology Wearable technology

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Finding biomarkers of exp.rience in animals

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Journal of Animal Science and Biotechnology 2024年第3期15卷 925-944页

作者： sarah Babington Alan J.Tilbrook Shane K.Maloney Jill N.Fernandes Tamsyn M.Crowley Luoyang Ding Archa H.Fox Song Zhang Elise A.Kho Daniel Cozzolino Timothy J.Mahony Dominique Blache School of Agriculture and Environment The University of Western AustraliaCrawleyWA 6009Australia Centre for Animal Science The Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia School of Veterinary Science The University of QueenslandGattonQLD 4343Australia School of Human Sciences The University of Western AustraliaCrawleyWA 6009Australia School of Medicine Deakin UniversityGeelongVIC 3217Australia p.ultry Hub Australia University of New EnglandArmidaleNSW 2350Australia College of Animal Science and Technology Yangzhou UniversityYangzhou 225009China Centre for Nutrition and Food Sciences The Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia

At a time when there is a growing p.blic interest in animal welfare,it is critical to have objective means to assess the way that an animal exp.riences a *** is critical to ensure ap.rop.iate animal welfare *** behavioural,p.ysiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative *** welfare is more than an absence of negative outcomes and an ap.rop.iate indicator should reflect the full sp.ctrum of exp.rience of an animal,from negative to *** this review,we draw from the knowledge of human biomedical science to p.op.se a list of candidate biological markers(biomarkers)that should reflect the exp.riential state of non-human *** p.op.sed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological *** also discuss p.actical challenges that must be addressed before any of these biomarkers can become useful to assess the exp.rience of an animal in real-life.

关键词： Animal exp.rience Animal welfare Biomarker Stress Welfare assessment

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