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Involvement of CrF2 signaling in enterocyte differentiation

World Journal of Gastroenterology 2017年第28期23卷 5127-5145页

作者： benjamin Ducarouge Marjolaine Pelissier-rota rebecca Powell Alain Buisson Bruno Bonaz Muriel Jacquier-Sarlin Equipe de l’apoptose du cancer et du développementCentre Léon Bérard Equipes des"Neuro-pathologies et Dysfonctions synaptiques"et du"Stress et des interactions neurodigestives" UniversitéGrenoble Alpes Equipes des"Neuropathologies et dysfonctions synaptiques"et du"Stress et des interactions neurodigestives" Université Grenoble Alpes and Grenoble Institut des Neurosciences-Inserm U1216 Service d’hépato-gastroentérologie Centre Hospitalier Universitaire de Grenoble

To determine the role of corticotropin releasing factor receptor (CrF2) in epithelial permeability and enterocyte cell *** this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8r, HT-29 and Caco-2 cell lines). Expression of CrF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CrF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CrF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TrITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mrNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor krüppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by rT-PCr and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric ***2 protein is preferentially expressed in undifferentiated epithelial cel

关键词： Urocortin3 Colon carcinoma cell lines Intercellular adhesion complexes Cell permeability Epithelial cell differentiation Corticotrophin releasing factor 2

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Epidemic Surveillance of Influenza Infections:A Network-Free Strategy—Hong Kong Special Administrative region,China,2008–2011

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China CDC weekly 2022年第46期4卷 1025-1031,I0002-I0005页

作者： Zhanwei Du Qi Tan Yuan Bai Lin Wang benjamin J.Cowling Petter Holme WHO Collaborating Centre for Infectious Disease Epidemiology and Control School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina Laboratory of Data Discovery for Health Limited(D24H) Hong Kong Science and Technology ParkHong Kong SARChina Department of Genetics University of CambridgeCambridgeUK Department of Computer Science Aalto UniversityEspooFinland

Introduction:The ease of coronavirus disease 2019(COVID-19)non-pharmacological interventions and the increased susceptibility during the past COVID-19 pandemic could be a precursor for the resurgence of influenza,potentially leading to a severe outbreak in the winter of 2022 and future *** recent increased availability of data on Electronic Health records(EHr)in public health systems,offers new opportunities to monitor individuals to mitigate ***:We introduced a new methodology to rank individuals for surveillance in temporal networks,which was more practical than the static *** targeting previously infected nodes,this method used readily available EHr data instead of the contactnetwork ***:We validated this method qualitatively in a real-world cohort study and evaluated our approach quantitatively by comparing it to other surveillance methods on three temporal and empirical *** found that,despite not explicitly exploiting the contacts’network structure,it remained the best or close to the best *** related the performance of the method to the public health goals,the reproduction number of the disease,and the underlying temporal-network structure(e.g.,burstiness).Discussion:The proposed strategy of using historical records for sentinel surveillance selection can be taken as a practical and robust alternative without the knowledge of individual contact behaviors for public health policymakers.

关键词： network policy networks

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Identification and optimization of a potent and highly selective D3 dopamine receptor agonist

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中国药理学与毒理学杂志 2017年第10期31卷 950-951页

作者： Amy E MOrITZ r benjamin FrEE Warren WEINEr Muzna BACHANI Trevor DOYLE Noel SOUTHALL Marc FErrEr Jonathan A JAVITCH Joseph STEINEr Ara ABrAMYAN Lei SHI Jeffrey AUBé Kevin FrANKOWSKI David r SIBLEY Molecular Neuropharmacology Section National Institute of Neurological Disorders and StrokeNational Institutes of Health Bethesda MD 20814 University of North Carolina Chapel Hill NC27599 Neurotherapeutic Development Unit National Institute of Neurological Disorders and StrokeNational Institutes of Health Bethesda MD 20814 National Center for Advancing Translational Sciences Rockville MD 20892 Columbia University New York NY 10032 Computational Chemistry and Molecular Biophysics Unit Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse National Institutes of Health Baltimore MD 21224

OBJECTIVE Dopamine receptors(Drs) are involved in the development and treatment of many neuropsychiatric *** available dopaminergic drugs modulate both DrD2 and DrD3,leading to side effects and uncertainty as to the roles each Dr subtype plays *** lab employed high throughput screening paradigms to discover highly selective modulators for the *** The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove rx Path Hunter?β-arrestin assay for compounds that activate the DrD3 without effects on the *** and counter-screens assessed selectivity and mechanisms of *** identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAr) study to increase potency while maintaining *** lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BrET)-based β-arrestin recruitment and G-protein activation assays as well as p-ErK *** neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell *** ML417 displays potent,DrD3-selective agonist activity in multiple functional *** and functional GPCr screens(>165 receptors) show ML417 has limited cross-reactivity with other ***417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell *** We have discovered and characterized ML417,a potent and highly selective DrD3 *** compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.

关键词： Dopamine receptor high throughput screening subtype selectivity neuroprotection

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乳糜泻及非乳糜泻性麦胶敏感症

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英国医学杂志中文版 2016年第7期19卷 383-396页

作者： benjamin Lebwohl Jonas F Ludvigsson Peter H r Green 夏志伟 Celiac Disease Center Department of Medicine Columbia University College of Physicians and Surgeons New York NY 10032 USA Department of Medical Epidemiology and Biostatisties Karolinska University Hospital and Karolinska Institute Stockholm Sweden Department of Pediatrics Orebro University Hospital Sweden 北京大学第三医院消化内科

乳糜泻是具有基因特异性的个体，因摄入麦胶而激发的多系统免疫异常。乳糜泻的患病率在近几十年来逐渐增加，目前在西方人群中已达1％。尽管与饮食卫生相关的多种环境因素值得怀疑，但其发病增加的原因并不明确。乳糜泻的发病机制涉及... 详细信息

乳糜泻是具有基因特异性的个体，因摄入麦胶而激发的多系统免疫异常。乳糜泻的患病率在近几十年来逐渐增加，目前在西方人群中已达1％。尽管与饮食卫生相关的多种环境因素值得怀疑，但其发病增加的原因并不明确。乳糜泻的发病机制涉及与饮食中的麦胶成分相关的原发性及适应性的免疫反应。该病的，临床表现多种多样，包括胃肠道症状、代谢性骨病、生育不能，以及其他多种多样的表现。虽然无麦胶食物对大多数患者的治疗有效，但这样的饮食令人烦恼并影响生活质量。因此。在疾病的不同阶段也需要非饮食疗法。本综述也总结了非乳糜泻性麦胶敏感症。对这一临床亚型的发病机制仍然缺乏了解，但这一现象使得无麦胶食品在人群中的应用受到重视。

关键词：乳糜泻非乳糜泻性麦胶敏感症治疗方法保健知识

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The role of super-spreaders in modeling of SArS-CoV-2

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Infectious Disease Modelling 2022年第4期7卷 778-794页

作者： François rousse Marcus Carlsson MagnusÖgren benjamin Kalischer Wellander School of Science and Technology Örebro University70182ÖrebroSweden Centre for Mathematical Sciences Lund UniversityBox 11822100LundSweden Hellenic Mediterranean University P.O.Box 1939GR-71004HeraklionGreece Centrum för forskning och utveckling(CFUG)region Gävleborg Sweden

In stochastic modeling of infectious diseases,it has been established that variations in infectivity affect the probability of a major outbreak,but not the shape of the curves during a major outbreak,which is predicted by deterministic models(Diekmann et al.,2012).However,such conclusions are derived under idealized assumptions such as the population size tending to infinity,and the individual degree of infectivity only depending on variations in the infectiousness *** this paper we show that the same conclusions hold true in a finite population representing a medium size city,where the degree of infectivity is determined by the offspring distribution,which we try to make as realistic as possible for *** particular,we consider distributions with fat tails,to incorporate the existence of *** also provide new theoretical results on convergence of stochastic models which allows to incorporate any offspring distribution with a finite variance.

关键词： COVID-19 Compartmental models SEIr SIr Offspring distribution for SArS-CoV-2

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澳大利亚初级卫生保健中癌症诊断风险工具的作用

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中国全科医学 2015年第3期18卷 241-242页

作者： Jon emery Peggy Chiang 本刊编辑部 University of Melbourn ParkvileVIC

背景以患者的症状和风险因素为基础,对癌症做出诊断是全科医学的核心职能之一。同样,为保持卫生系统的成本效益,全科医生应避免对不太可能患癌症的人群进行过度检查,或对很可能没有患癌症的患者进行转诊。在初级卫生保健工作中诊断癌症... 详细信息

背景以患者的症状和风险因素为基础,对癌症做出诊断是全科医学的核心职能之一。同样,为保持卫生系统的成本效益,全科医生应避免对不太可能患癌症的人群进行过度检查,或对很可能没有患癌症的患者进行转诊。在初级卫生保健工作中诊断癌症并非易事,因为许多癌症的症状是由很常见的良性因素引起的。目的在初级卫生保健中,评估癌症诊断风险工具的作用。讨论某些癌症,如肺癌、胰腺癌、卵巢癌和骨髓瘤,很难在早期做出诊断。现有的国家癌症指南强调,尽可能对那些具有"危险信号"症状,可能已患癌症的患者做出识别。在初级卫生保健实践中,开发了一些验证风险的工具,以患者的症状和风险因素为基础,对癌症做出诊断。在初级卫生保健实践中,这些工具在辅助癌症诊断方面可能是有用的,也减少了对患癌风险非常低的患者进行过度检查。

关键词：初级卫生保健肿瘤诊断

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Observing the stages of bystander intervention in virtual reality simulation

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World Journal of Emergency Medicine 2019年第3期10卷 145-151页

作者： David G. Buckler Alfredo Almodovar Jr Paul Snobelen benjamin S. Abella Audrey Blewer Marion Leary Center for resuscitation Science University of Pennsylvania Philadelphia PA 19104 USA Peel regional Paramedic Service 1600 Bovaird Dr. E Brampton ON L6R 3S8 Canada Department of Community & Family Medicine Duke University Medical Center DUMC 2914 Durham NC 27710 USA School of Nursing University of Pennsylvania 418 Guardian Drive Philadelphia PA 19104 USA

BACKGrOUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a problem, interpreting when it is appropriate to intervene, recognizing personal responsibility to intervene, and knowing how to intervene. Using virtual reality (Vr) to simulate emergencies such as sudden cardiac arrest (SCA) can be used to study these stages. METHODS: In a secondary analysis of an observational cohort study, we analyzed bystander self-effi cacy for stages of BI before and after simulated SCA. Each subject participated in a singleplayer, immersive, Vr SCA scenario. Subjects interacted with simulated bystanders through voice commands (“call 911”,“get an AED”). Actions taken in scenario, like performing CPr, were documented. Scenario BI actions were compared based on dichotomized comfort/discomfort. rESULTS: From June 2016 to June 2017, 119 subjects participated. Average age was 37±14 years, 44% were female and 46% reported CPr training within 2 years. During the scenario, 98%“noticed the event” and “interpreted it as a problem”, 78%“took responsibility”, and 54%“possessed the necessary skills”. Self-effi cacy increased from pre- to post-scenario: noticing the event increased from 80% to 96%;interpreting as a problem increased from 86% to 97%;taking responsibility increased from 56% to 93%;possessing necessary skills increased from 47% to 63%(Prespond to an SCA event increased pre- to post-scenario. Bystanders who reported feeling comfortable “taking responsibility to intervene” during an emergency were more likely to take action during a simulated emergency.

关键词： Virtual reality Bystander intervention Emergency preparedness

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Strip-coalesced interior zone model for two unequal collinear cracks weakening piezoelectric media

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Applied Mathematics and Mechanics(English Edition) 2014年第10期35卷 1249-1260页

作者： r.r.BHArGAVA K.JANGID Department of Mathematics Indian Institute of Technology roorkee

In this paper, a mathematical strip-saturation model is proposed for a poled transversely isotropic piezoelectric plate weakened by two impermeable unequal-collinear hairline straight cracks. remotely applied in-plane unidirectional electromechanical loads open the cracks in mode-I such that the saturation zone developed at the interior tips of cracks gets coalesced. The developed saturation zones are arrested by distributing over their rims in-plane normal cohesive electrical displacement. The problem is solved using the Stroh formalism and the complex variable technique. The expressions are derived for the stress intensity factors （SIFs）, the lengths of the saturation zones developed, the crack opening displacement （COD）, and the energy release rate. An illustrative numerical case study is presented for the poled PZT-5H ceramic to investigate the effect of prescribed electromechanical loads on parameters affecting crack arrest. Also, the effect of different lengths of cracks on the SIFs and the local energy release rate （LErr） has been studied. The results obtained are graphically presented and analyzed.

关键词： crack opening displacement (COD) energy release rate piezoelectric ce-ramic Stroh formalism saturation zone unequal-collinear crack

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Tissue and regional expression patterns of dicistronic trNA–mrNA transcripts in grapevine (Vitis vinifera) and their evolutionary co-appearance with vasculature in land plants

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Horticulture research 2021年第1期8卷 1715-1729页

作者： Pastor Jullian Fabres Lakshay Anand Na Sai Stephen Pederson Fei Zheng Alexander A.Stewart benjamin Clements Edwin r.Lampugnani James Breen Matthew Gilliham Penny Tricker Carlos M.rodriguez Lopez rakesh David School of Agriculture Food and WineUniversity of AdelaideAdelaideSAAustralia Environmental Epigenetics and Genetics Group Department of HorticultureCollege of AgricultureFood and EnvironmentUniversity of KentuckyLexingtonKYUSA ArC Centre of Excellence in Plant Energy Biology Waite Research Institute&School of AgricultureFood and WineUniversity of AdelaideAdelaideSAAustralia Bioinformatics Hub School of Biological SciencesUniversity of AdelaideAdelaideSAAustralia School of Biosciences University of MelbourneParkvilleVIC 3010Australia ArC Industrial Transformation Training Centre in Innovative Wine Production Waite Research Institute&School of AgricultureFood and WineUniversity of AdelaideAdelaideSAAustralia

Transfer rNAs(trNA)are crucial adaptor molecules between messenger rNA(mrNA)and amino *** evidence in plants suggests that dicistronic trNA-like structures also act as mobile signals for mrNA transcripts to move between distant ***-transcription is not a common feature in the plant nuclear genome and,in the few cases where polycistronic transcripts have been found,they include non-coding rNA species,such as small nucleolar rNAs and *** is not known,however,the extent to which dicistronic transcripts of trNA and mrNAs are expressed in field-grown plants,or the factors contributing to their *** analysed trNA–mrNA dicistronic transcripts in the major horticultural crop grapevine(Vitis vinifera)using a novel pipeline developed to identify dicistronic transcripts from high-throughput rNA-sequencing *** identified dicistronic trNA–mrNA in leaf and berry samples from 22 commercial *** the 124 trNA genes that were expressed in both tissues,18 trNA were expressed forming part of 19 dicistronic trNA–*** presence and abundance of dicistronic molecules was tissue and geographic sub-region *** leaves,the expression patterns of dicistronic trNA–mrNAs significantly correlated with trNA expression,suggesting that their transcriptional regulation might be *** also found evidence of syntenic genomic arrangements of trNAs and protein-coding genes between grapevine and Arabidopsis thaliana,and widespread prevalence of dicistronic trNA–mrNA transcripts among vascular land plants but no evidence of these transcripts in non-vascular *** suggests that the appearance of plant vasculature and trNA–mrNA occurred concurrently during the evolution of land plants.

关键词： dic Vitis arrangement

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饲养对奶成分的影响

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国外畜牧学（草食家畜） 1992年第5期 44-45页

作者： BY r.S.emery 钱冬梅

奶牛的乳腺是奶牛利用饲料营养物质合成奶成分的主要场所。营养状况决定着奶产量和各种奶成分的含量。然而,非营养因素诸如遗传、泌乳天数、胎次、感染、分泌细胞数及温度、湿度等的作用常常超过营养对奶成分的影响。母牛个体乳汁中乳... 详细信息

奶牛的乳腺是奶牛利用饲料营养物质合成奶成分的主要场所。营养状况决定着奶产量和各种奶成分的含量。然而,非营养因素诸如遗传、泌乳天数、胎次、感染、分泌细胞数及温度、湿度等的作用常常超过营养对奶成分的影响。母牛个体乳汁中乳脂率的变化趋于3—7天为一个周期。

关键词：乳牛奶成分

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