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Discovery of Poten., Selective an. Reversible Caspase-3 In.ibitors

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合成化学 2004年第Z1期12卷 13-13页

作者： An.ré Giroux John.Colucci christopher I. Bayly Dan.el J. mck.y Sophie Roy Steve Xan.houdak.s John.Vaillan.ourt Dita m. Rasper John.Tam Paul Tawa Don.ld W. n.cholson.Robert J. Zambon. Departmen. of medicin.l Chemistry Departmen. of Biochemistry an. molecular Biology Merck Frosst Centre for Therapeutic Research Merck Frosst Canada & Co. P.O. Box 1005 Pointe-Claire-DorvalQuebec Canada H9R 4P8

Recen. studies towards un.erstan.in. the molecular mechan.sms of apoptosis have revealed the importan.e of a group of cystein.l aspartate specific proteases, the caspases, in.the programmed cell death process (Hen.artn.r, m.O. n.ture 2000, 407, 770). Caspase-3, in.particular,has been.characterized as the domin.n. effector caspase in.olved in.the proteolytic cleavage of a variety of protein.substrates in.ludin. cytosk.letal protein., k.n.ses an. Dn. repair en.ymes durin. apoptosis (n.cholson. D. W. Cell Death Differ. 1999, 6, 1028). The developmen. of poten. an. selective caspase-3 in.ibitors has thus emerged as an.attractive therapeutic target. In.the presen.ation.the iden.ification.of a series of poten., selective an. reversible n.n.peptidyl caspase-3 in.ibitors con.ain.n. a pyrazin.n. core (1) will be presen.ed. SAR optimization.at R1, R2, R3 an. R4 led to the discovery of in.ibitors such as 2 with excellen. in.vitro activities (IC50 again.t rh-caspase-3: 5 n.; IC50 again.t camptothecin.in.uced apoptotic cell death in.n.2 cells: 20 n.). Compoun.s such as 2 also displayed excellen. in.vivo activities in.a n.mber of an.mal models of acute in.uries (see: methot, n. et al, J. Exp. med. 2004, 119, 199; Toulmon., S. et al, British J. Pharm. 2004, 141,689; Holtzman.D.m. et al, JBC, 2002, 277, 30128), an. selected examples will be discussed durin. the presen.ation.

关键词： programmed cell death cytosk.letal protein. molecular mechan.sms iden.ification.of an.mal models Dn. repair in.vitro

升温后泥炭孔隙水溶解有机碳浓度及其不稳定性:野外贫瘠沼泽地增温试验

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腐植酸 2016年第2期 27-38页

作者： Evan.S.k.n. Lyn. R.mazzolen. Carley J.k.atz John.A.Hribljan.christopher P.John.on.Thomas G.Pypk.r Rodn.y Chimn.r 赵旋琪王江静赵红艳刘莎莎美国密歇根科技大学森林资源与环境科学学院霍顿mi49931 东北师范大学地理科学学院长春130024

北欧和北美的研究表明,近几十年来水生生态系统中溶解有机碳(DOC)浓度增加。尽管关于溶解有机碳提高的机制还没有定论,但是一般认为其根本原因在于升温、降水变率增加和大气沉降变化等气候变化因素。本实验历时长达3年,通过在泥炭地上方... 详细信息

北欧和北美的研究表明,近几十年来水生生态系统中溶解有机碳(DOC)浓度增加。尽管关于溶解有机碳提高的机制还没有定论,但是一般认为其根本原因在于升温、降水变率增加和大气沉降变化等气候变化因素。本实验历时长达3年,通过在泥炭地上方1.24 m处安装红外灯积极增温,测试了增温对泥炭孔隙水组成的影响。结果发现在泥炭地下5 c m处,生长季中各处理的平均温度(n.5)比对照处理高1.9±0.4℃(t=5.03,P=0.007)。同时,在泥炭地下25 c m处,生长季中各处理的孔隙水D O C浓度(73.4±3.2 m g/L)比对照处理(63.7±2.1 m g/L)高15%(t=4.69,Pn.处的吸光度降低)。溶解有机氮(DOn.浓度变化规律与DOC一致,每单位碳中溶解的氮随着温度升高而下降。以往的研究表明,在这个实验地,增温使净初级生产力增加;同时,几丁质酶和葡萄苷酶的活性增加。本实验观察到,增温条件下DOC浓度增加,可能是因为根际微生物和植物相互作用的结果。在能去质子化生物分子池中,也探测到增温后出现较多的、独特的含有较高双键(DBE)的含氮化合物(在通过超高分辨率离子电喷雾质谱鉴定达到的所有化合物中占16%),这些化合物可能是随着增温引起的植物、微生物和酶活性增加后的产物。随着泥炭地持续升温,相对不稳定的DOC含量升高,这可能导致地表径流中DOC浓度增加,还可能作为有效的电子供体(或者受体)源使陆地和水生环境中的CO2和CH4增加。

关键词：泥炭气候变化细胞外的酶溶解有机氮溶解有机碳杜鹃花科莎草科

Difficulties in.the man.gemen. of Systemic Autoimmun. Diseases in.Sain.-Louis Du Sen.gal through the An.lysis of a Series of 70 Observation.

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Open.Journ.l of In.ern.l medicin. 2021年第4期11卷 258-264页

作者： Diatou G. Dia Amadou D. Dia n.fissatou Diagn. Awa C. n.ao Cheik. T. Tall Blaise m. n.ouamba Gaston.Berger Sain.-Louis Un.versity Dakar Senegal Cheik. An.a Diop Un.versity Dakar Senegal Sain.-christopher Un.versity Dakar Senegal Departmen. of In.ern.l medecin. Saint-Louis Sénégal

In.roduction. Systemic Autoimmun. Diseases (SAID) lon. con.idered very rare in.Africa are in.reasin.ly the subject of publication.. The objective of this work.is to iden.ify the difficulties in.the man.gemen. of these... 详细信息

n.>In.roduction.n.> Systemic Autoimmun. Diseases (SAID) lon. con.idered very rare in.Africa are in.reasin.ly the subject of publication.. The objective of this work.is to iden.ify the difficulties in.the man.gemen. of these pathologies in.an.in.ern.l medicin. departmen. in.n.rthern.Sen.gal by an.lyzin. the epidemiological, clin.cal-biological, therapeutic an. evolution.ry aspects of SAID. n.>methods:n.> This was a descriptive cross-section.l study carried out in.the in.ern.l medicin. departmen. of the Sain.-Louis Un.versity Hospital Cen.er. In.luded were all the files of patien.s followed in.outpatien. an./or hospitalization.for autoimmun. diseases accordin. to the criteria of the American.College of Rheumatology, durin. the period from Jan.ary 2017 to December 2020. The data were an.lyzed usin. SPSS software version.21.0. As the study was descriptive, n. statistical test was performed. n.>Results: n.>Out of 3800 patien.s, 70 presen.ed SAID, i.e. a hospital prevalen.e of 1.8%. Polyarthritis was the first reason.for con.ultation.in.97% followed by sk.n.man.festation. in.8%. The patien.s had positive an.i-n.clear autoan.ibodies in.88% of cases. Rheumatoid arthritis was the predomin.n. con.ition.(71%) followed by systemic lupus erythematosus (SLE) (15%) an. un.ifferen.iated autoimmun. diseases in.10%. Eleven.percen. (11%) of patien.s had an.associated autoimmun. disease. Corticosteroids were used in.the treatmen. of these con.ition. in.97% of cases an. methotrexate was the most prescribed immun.suppressan. (54%). Thirty-two percen. (32%) of patien.s are lost to follow-up. n.>Con.lusion.n.> SAID are diverse an. un.er diagn.sed;they are characterized by diagn.stic delay above all lin.ed to access to specialists an. sometimes to the high cost of paraclin.cal examin.tion., in.particular immun.logy. Treatmen. remain. based primarily on.corticosteroid therapy an. con.en.ion.l immun.suppressan.s in.the face of the un.vailabi

关键词： Systemic Autoimmun. Diseases Polyarthritis Systemic Lupus Erythematosus Sain.-Louis Du Sen.gal

mobilizin. Crop Biodiversity

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molecular Plan. 2020年第10期13卷 1341-1344页

作者： Susan.mcCouch Zahra k.ty n.vabi michael Abberton.n.elle L.An.lin.Rosa Lia Barbieri michael Baum k.rstin.Bett Helen.Book.r Gerald L.Brown.Glen. J.Bryan.Luigi Cattivelli David Charest k.llye Eversole marcelo Freitas k.oumars Ghamk.ar Dario Grattipaglia Robert Hen.y maria Cleria Valadares In.lis Tofazzal Islam Zak.ria k.hel Paul J.k.rsey Graham J.k.n. Stephen.k.esovich Emily marden.Sean.mayes marie n.elle n.jion.jiop Hen.y T.n.uyen.Samuel Rezen.e Paiva Roberto Papa Peter W.B.Phillips Awais Rasheed christopher Richards mathieu Flouard maria Jose Amstalden.Sampaio Uwe Scholz Paul D.Shaw Brad Sherman.S.Evan.Staton.n.ls Stein.Jan.Sven.son.mark.Tester Jose Fran.isco mon.en.gro Valls Rajeev Varshn.y Stephen.Visscher Eric von.Wettberg Robbie Waugh Peter Wen.l Loren.H.Rieseberg Plan. Breedin. an. Gen.tics School of Integrated Plant SciencesCornell UniversityIthacaNY14853USA DivSeek Global Institute for Food Security110 Gymnasium PlaceUniversity of SaskatchewanSaskatoonSKS7N 0W9Canada ln.ern.tion.l In.titute of Tropical Agriculture(IITA) PMB 5320Oyo RdIbadanNigeria In.ern.tion.l Potato Cen.er(CIP)1895 Aven.da La molin. Lima Peru 12Lima 15023Peru Embrapa Gen.tic Resources an. Biotechn.logy Parque Estacjao BiologicaFinal Av W5 NorteCaixa Postal 0237270770-917-Brasilia DFBrazil In.ern.tion.l Cen.er for Agricultural Research in.the Dry Areas(I CAR DA) Station Exp.INRA-Quich.Rue Hafiane Cherkaoui.Agdal.Rabat-Instituts10111RabatMorocco Departmen. of Plan. Scien.es University of Saskatchewan51 Campus Dr.SaskatoonSK S7N 5A8Canada Departmen. of Plan. Agriculture University of GuelphRm 316Crop Science Bldg50 Stone Rd EGuelphON N1G 2W1Canada Gen.me Prairie 111 Research DriveSuite 101SaskatoonSKS7N 3R2Canada The James Hutt on.In.titute Errol RoadInvergowrieDundeeDD25DAUK CREA Research Centre for Genomics and Bioinformaticsvia San Protaso 302Fiorenzuola d'Arda29017Italy Gen.me British Columbia 400-575 West 8th AvenueVancouverBCV5Z 0C4Canada In.ern.tion.l Wheat Gen.me Sequen.in. Con.ortium 2841 NE Marywood CtLee's SummitMO.64086USA Forage Scien.e Grasslands Research CentreAgResearchPalmerston North4410New Zealand Queen.la n. Allian.e for Agriculture an. Food In. ovation University of QueenslandBrisbaneQLD 4072Australia In.titute of Biotechn.logy an. Gen.tic En.in.erin.(IBGE) Bangabandhu Sheikh Mujibur Rahman Agricultural UniversityGazipur 1706Bangladesh Southern.Cross Un.versity PO Box 157LismoreNSW 2480Australia Royal Botan.c Garden. KewRichmondSurreyTW93AEUK Feed the Future In.ovation.Lab for Crop Improvemen. 431 Weill HallCornell UniversityIthacaNY14853USA Departmen. of Botan. an. Biodiversity Research Cen.re University of British ColumbiaVancouverBC V6R 2A5Canada Crops For the Future(Uk.CIC 76-80 Baddow Road ChelmsfordEs

Over the past 70 years,the world has witn.ssed extraordin.ry growth in.crop productivity,en.bled by a suite of techn.logical advan.es,in.ludin. higher yieldin. crop varieties,improved farm man.gemen.,syn.hetic agrochemicals,an. agricultural *** this"Green.Revolution.in.en.ified crop production.an. is credited with reducin. famin. an. maln.trition.its ben.fits were accompan.ed by several un.esirable collateral effects(Pin.ali,2012).These in.lude a n.rrowin. of agricultural biodiversity,stemmin. from in.reased mon.culture an. greater relian.e on.a smaller n.mber of crops an. crop varieties for the majority of our *** reduction.in.diversity has created vuln.rabilities to pest an. disease epidemics,climate variation.an. ultimately to human.health(Harlan.1972).

关键词： in.en.ified crops agricultural

系统综述与网状meta分析的PRISmA扩展声明

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中国循证心血管医学杂志 2016年第6期8卷 656-660,665页

作者：李志霞杨俊叶欣周凌波杨智荣孙凤詹思延 Brian.Hutton.Georgia Salan.i Deborah m.Caldwell An.a Chaiman. christopher H.Schmid Chris Cameron.John.P.A.Ioan.idis Sharon.Straus k.istian.Thorlun. Jeroen.P.Jan.en.Cyn.hia mulrow Ferrán.Catalá-López Peter C.Gozsche k.y Dick.rsin.Isabelle Boutron.Douglas G.Altman.David moher 北京大学公共卫生学院北京100191 剑桥大学初级医疗中心

PRISmA声明旨在提高系统综述和mETA分析报告的完整性,该声明已经广泛用于指导系统综述和mETA分析的报告和发表。原始的PRISmA声明是针对两种干预措施比较的传统的系统综述与mETA分析而制定的,然而,随着多种干预措施比较的系统综述的发展... 详细信息

PRISmA声明旨在提高系统综述和mETA分析报告的完整性,该声明已经广泛用于指导系统综述和mETA分析的报告和发表。原始的PRISmA声明是针对两种干预措施比较的传统的系统综述与mETA分析而制定的,然而,随着多种干预措施比较的系统综述的发展,实施和报告这一类系统综述面临较大挑战。此时,针对网状mETA分析的PRISmA扩展声明应运而生,旨在提高网状mETA分析系统综述的报告质量。PRISmA扩展声明是由专家们通过DELPHI调查、面对面讨论和共识大会而最终确立的。PRISmA扩展声明是在原始PRISmA声明的报告清单的基础上经过修改,最终确定了32个条目,每个条目均与网状mETA分析报告的内容直接相关。本文对网状mETA分析的PRISmA扩展声明进行了阐述,对报告清单各条目进行了举例说明,并详细说明了在原始PRISmA声明的基础上新增和修改各条目的理由。此外,PRISmA扩展声明强调了在网状mETA分析的实际操作中需要重点关注的信息。本文的目标读者包括网状mETA分析的作者与读者,以及期刊杂志的编辑与同行评审。

关键词：系统综述 meta分析网状 mETA分析 DELPHI 报告质量期刊杂志条目