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Pink1 Rescues Gal4-Induced Developm.ntal Defects in the DrosophilaEye

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Advances in Parkinson's Disease 2015年第3期4卷 43-48页

作者： amy m. todd Brian E. Staveley Departm.nt of Biology Memorial University of Newfoundland St. John’s Canada

Parkinson disease pathology often includes the presence of ubiquitin-positive, α-synuclein-enriched inclusions in the rem.ining neurons. Pink1 (also identified as PARK6) encodes a serinethreonine kinase involved in m.tochondrial protection that works with parkin to ubiquitinate various proteins, prom.ting m.tophagy. The parkin protein works to tag cystolic proteins for degradation, and previous work in our laboratory has shown the ability of parkin to rescue a Gal4-induced phenotype. To further investigate the role of Pink1 in protection against toxic proteins, we have perform.d expression studies to determ.ne the effects of increases and decreases in Pink1 on the Gal4-induced phenotype consisting of developm.ntal defects in the Drosophila eye. Our results show that Pink1 is able to rescue the Gal4-induced phenotype, highlighting a protective role for Pink1 against toxic proteins. When expressing low levels of Gal4, reductions in Pink1 or parkin are not able to induce a phenotype. This suggests that Pink1 or parkin m.y counter Gal4 effects despite reductions, or that the effects of low level Gal4 m.y be alleviated by an alternative m.chanism. m.reover, the Pink1 m.chanism.of action during differing types of cell stress, including degradation of toxic proteins, warrants further investigation.

关键词： Drosophila m.lanogaster Pink1 Parkin Gal4 Toxic Protein Parkinson Disease

m.lecular Docking Studies on Streptom.cin Antileishm.nial Activity

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Open Journal of Physical Chem.stry 2024年第2期14卷 36-48页

作者： todd A. Young m.tthew George Jr. Ayele Gugssa William.m. Southerland Yayin Fang Clarence m. Lee Departm.nt of Biology Howard University Washington DC United States Departm.nt of Biochem.stry and m.lecular Biology Howard University Washington DC United States

Resistance to pentavalent antim.nial drugs and the lack of vaccines m.ke it urgent to find novel therapeutic options to treat Leishm.niasis, a tropical disease caused by the Leishm.nia protozoan parasite. The study reported here is to investigate if Streptom.cin, an am.noglycoside, and Am.hotericin B, the second-line treatm.nt drug, exhibit antileishm.nial activity through a sim.lar m.chanism. By using m.E (m.lecular Operating Environm.nt), we perform.d m.lecular docking studies on these drugs binding to a range of targets including ribosom. targets in Leishm.nia and H. sapiens. Our study shows that the two drugs do not bind to the sam. pockets in Leishm.nia targets but to the sam. pockets in the hum.n ribosom., with som. differences in interactions. m.reover, our 2D m.ps indicated that Am.hotericin B binds to the A-site in the hum.n cytoplasm.c ribosom., whereas streptom.cin does not.

关键词： Leishm.niasis Streptom.cin Am.hotericin B m.lecular Docking Am.noglycosides Antileishm.nial

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中草药 2024年第1期55卷 181-189页

作者：崔高畅 amy Yi Hsan Saik 张新慧马玉玮杨早东姑阿都拉曼大学m.Kandiah医学与健康科学学院雪兰莪加影43000 宁夏医科大学药学院宁夏银川750004

目的利用生物信息学方法筛选湿性年龄相关性黄斑变性(wet age-related m.cular degeneration,w Am.)的氧化应激相关差异表达基因及靶向中药,以期为wAm.的预防和治疗提供新思路。方法从GEO数据库中筛选数据集,利用R软件lim.a包筛选差异基... 详细信息

目的利用生物信息学方法筛选湿性年龄相关性黄斑变性(wet age-related m.cular degeneration,w Am.)的氧化应激相关差异表达基因及靶向中药,以期为wAm.的预防和治疗提供新思路。方法从GEO数据库中筛选数据集,利用R软件lim.a包筛选差异基因,从Genecard数据库筛选氧化应激差异基因,并利用韦恩图得到共有基因。应用m.tascape对氧化应激差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genom.s,KEGG)分析,并通过String数据库构建蛋白质相互作用(protein-protein interaction,PPI)网络,再通过Cytoscape软件筛选出wAm.中氧化应激的关键(Hub)基因。采用GSE103060数据集验证Hub基因的差异表达。利用Corem.ne m.dical预测靶向中药。结果经筛选共得到差异表达基因1874个,其中上调基因747个,下调基因1127个。KEGG富集分析表明,差异表达基因主要富集于细胞外基质受体相互作用、黏附斑激酶通路、河马(Hippo)信号通路、晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路、钙信号通路和磷脂酰肌醇-3-羟激酶(phosphatidylinositol-3-hydroxykinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路。通过PPI网络筛选得到与w Am.氧化应激密切相关的8个Hub基因,分别为IL6、EGFR、HIF1A、APOE、FN1、PPARG、EDN1和NGF。最后在GSE103060数据集中验证了以上Hub基因的显著差异表达。利用Corem.ne m.dical预测人参、黄芪、枸杞子、丹参、银杏叶等可作为预防或治疗wAm.的靶向中药。结论通过对w Am.芯片的挖掘和生物信息分析,差异基因主要富集于氧化应激的相关通路与wAm.的氧化应激相关基因引起的。防治wAm.的首选中药为人参、黄芪、枸杞子、丹参和银杏叶等26种。这将对理解和探索wAm.的中医药防治策略有重要意义。

关键词：生物信息学湿性年龄相关性黄斑变性氧化应激中药筛选人参黄芪枸杞子丹参银杏叶

Im.ower210:A phase Ⅲ study of second-line atezolizum.b vs. docetaxel in East Asian patients with non-sm.ll cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan Chen Jianxing He Jifeng Feng Yiping Zhang Liyan Jiang Hongm.ng Pan Jianhua Chang Jian Fang amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Departm.nt of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Departm.nt of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Departm.nt of m.dical Oncology Jiangsu Cancer HospitalNanjing 210009China Departm.nt of m.dical Oncology Zhejiang Cancer HospitalHangzhou 330022China Departm.nt of Pulm.nary m.dicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Departm.nt of m.dical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Departm.nt of m.dical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Departm.nt of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Developm.nt Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: Im.ower210(NCT02813785) explored the efficacy and safety of single-agent atezolizum.b *** as second-line treatm.nt for advanced non-sm.ll cell lung cancer(NSCLC) in East Asian ***: Key eligibility criteria for this phase Ⅲ, open-label, random.zed study included age ≥18 years;histologically docum.nted advanced NSCLC per the Union for International Cancer Control/Am.rican Joint Com.ittee on Cancer staging system.7th edition);Eastern Cooperative Oncology Group perform.nce status of 0 or 1;and disease progression following platinum.based chem.therapy for advanced or m.tastatic NSCLC. Patients were random.zed 2:1 to receive either atezolizum.b(1,200 m.) or docetaxel(75 m./m.(2)). The prim.ry study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epiderm.l growth factor receptor expression(ITT EGFR-WT) and in the overall ITT ***: m.dian OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] m.nths in the atezolizum.b arm.n=312) and 9.9(95% CI, 7.8-13.9) m.nths in the docetaxel arm.n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. m.dian OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) m.nths with atezolizum.b treatm.nt and 11.1(95% CI, 8.4-14.2) m.nths(n=377) with docetaxel treatm.nt(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatm.nt-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizum.b arm.and 50.0% of patients in the docetaxel ***: Im.ower210 did not m.et its prim.ry efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizum.b was com.aratively m.re tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizum.b East Asia non-sm.ll cell lung cancer program.ed death-ligand 1 inhibitors m.noclonal antibody

Land tenure and landscape change:a com.arison of public-private lands in the southern High Plains

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Ecological Processes 2016年第1期5卷 139-152页

作者： todd D.Fagin Jacqueline m.Vadjunec Nicole m.Colston Kathyrn Wenger amy Graham Oklahom. Biological Survey University of Oklahoma111 E.Chesapeake StNorman 73019OKUSA Departm.nt of Geography Oklahoma State University337 Murray HallStillwater 74078OKUSA

Introduction:Long-term.drought in the southern Great Plains increases the vulnerability of coupled hum.n-environm.nt system. at a variety of *** better understandings of the dynam.cs at regional scales will becom. increasingly im.ortant as long-established land-use regim.s break down in the face of clim.te change,resource depletion,and evolving *** dem.nstrate differential vulnerability during drought periods,this study hypothesized that observed increases in woody vegetation in grasslands would vary across land-tenure *** argue that differences in State Trust Land governance,in part,lead to differential land m.nagem.nt practices that contribute to landscape ***:The study area encom.asses adjacent counties,Cim.rron County in Oklahom. and Union County in New m.xico,with sim.lar clim.te variability and agricultural *** analyzed National Land Cover Database(NLCD)land-cover m.ps from.1992 and 2011 to assess changes in landscape com.osition and structure between 1992 and ***:During both years under consideration,each county in the study region,across various land-tenure regim.s,was dom.nated by herbaceous ***,there were changes in both com.osition and structure across the whole study area,in particular losses of herbaceous vegetation and increases in woody *** greatest gains in woody vegetation occurred in State Trust Lands of Cim.rron ***,the data suggest a fragm.ntation of herbaceous vegetation and a coalescing of shrubland ***:Research about the influence of land tenure on land m.nagem.nt decisions,specifically the role of State Trust Land leases in overgrazing,inform. the broader context of drought m.nagem.nt in the southern Great *** include continued research to highlight the specific m.chanism. of land-tenure governance that drive landscape change.

关键词： Drought Land tenure Agriculture Landscape com.osition Landscape structure Southern Great Plains Grasslands Socio-ecological vulnerability National Land Cover Database(NLCD)

始新世中期安宁河断裂冲断变形特征及其构造意义:来自断层泥自生伊利石K-Ar定年的证据

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地学前缘 2024年第4期31卷 297-313页

作者：童馗李智武刘树根 I.Tonguç UYSAL 施泽进李金玺 Andrew todd 武文慧王自剑刘升武李轲华天成都理工大学油气藏地质及开发工程全国重点实验室四川成都610059 成都理工大学地质资源与地质工程博士后流动站四川成都610059 CSIRO Energy 26 Dick Perry AvenueKensingtonWA 6151Australia 西华大学四川成都610039 School of the Environm.nt The University of QueenslandBrisbaneQLD 4072Australia 西南油气田分公司勘探开发研究院四川成都610051

青藏高原及其周缘褶皱-冲断带变形方式和时限是验证高原形成众多大陆岩石圈变形动力学端员模型的关键。近年发展起来的断层泥自生伊利石K-Ar定年技术为精确限定褶皱-冲断带变形时限提供了有效手段。鲜水河—安宁河—小江断裂系作为伴随... 详细信息

青藏高原及其周缘褶皱-冲断带变形方式和时限是验证高原形成众多大陆岩石圈变形动力学端员模型的关键。近年发展起来的断层泥自生伊利石K-Ar定年技术为精确限定褶皱-冲断带变形时限提供了有效手段。鲜水河—安宁河—小江断裂系作为伴随印度-欧亚板块碰撞造山和高原物质侧向挤出过程形成的大型左旋走滑断裂系,其变形过程可为解译印度-欧亚板块碰撞远程应力向东传递方式提供关键证据。本文选取安宁河断裂冕宁—西昌段作为研究对象,在详细构造解析以明确其构造运动学特征的基础上,开展了断层泥自生伊利石K-Ar定年研究,以期精确限定安宁河断裂脆性变形的时间。构造解析表明安宁河断裂在近EW向挤压作用下经历了冲断变形,断层带发育碎斑岩和断层泥,指示为脆性变形。安宁河断裂不同粒级断层泥样品的黏土矿物学和伊利石K-Ar定年分析揭示,随着样品粒级减小,高温2m.型伊利石含量相对低温1m.1m.型伊利石含量逐渐减少,其K-Ar年龄总体呈变年轻趋势,表明不同粒级伊利石K-Ar年龄是由碎屑2m.型和自生1m.1m.型两个多型端员组成的混合年龄。伊利石年龄分析获得自生1m.1m.型伊利石的年龄为(42.6±9.4)m.,表明安宁河断裂经历了始新世中期的冲断变形。结合前人构造变形、沉积学、低温热年代学和古地磁等研究,我们认为始新世中期青藏高原腹地及其周缘褶皱-冲断带发生准同期的构造挤压变形,其动力学机制可能与印度-欧亚板块硬碰撞以及青藏高原地块的陆内俯冲所导致的先存构造带活化有关。始新世中期安宁河断裂发生冲断变形直接证明印度-欧亚板块碰撞初期的远程应力已传递至青藏高原东南缘地区。

关键词：安宁河断裂断层泥自生伊利石 K-Ar定年始新世中期

New m.thodological Approach to Investigation of Kinetics of REE Extraction in Nonstationary Conditions

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Journal of Rare Earths 2007年第4期25卷 385-391页

作者： Kopyrin A A Fom.chev A A Afonin m.A todd T A Saint-Petersburg Institute of Technology Idaho National Laboratory

The influence of periodical oscillations of the tem.erature on extraction and stripping processes in the extraction system. was studied. Two extraction system. were investigated：（1） 6 m.l · L^-1 NaNO3-Nd（NO3）3-Pr（NO3）3-TBP kerosene and （2） [Nd（NO3）3 · 3TBP] -[ Pr（NO3）3 · 3TBP] -kerosene - 0.1 m.l · L^-1 HNO3. m.them.tical m.deling of the nonstationary m.m.rane extraction has been enhanced by including the dependence of the extraction rate constants on tem.erature. The values of activation energy for direct and reverse extraction and stripping reactions of Pr and Nd were calculated from.experim.ntal tem.oral dependencies of m.tal concentration and tem.erature by solving the reverse kinetics problem.using the proposed m.them.tical m.del, A series of experim.nts with periodical oscillations of the tem.erature on the extraction system.for the separation of rare earth elem.nts （REE） using bulk liquid m.m.rane between two extractors were perform.d. The m.them.tical m.del adequately describes the experim.ntal data. The optim.zation of the extraction process for separation of REE by liquid m.m.rane, under the influence of periodical oscillation of the tem.erature, was m.de based on the extraction rate constants and activation energies. The optim.l conditions of separation by liquid m.m.rane were found： frequency and am.litude of therm.l oscillations, liquid m.m.rane flow rate, and optim.l ratio between organic and aqueous phase in extractors.

关键词： kinetics extraction non-stationary rare earths

Gradients in predation risk in a tropical river system

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Current Zoology 2018年第2期64卷 213-221页

作者： amy E. DEACON Faith A. m. JONES Anne E. m.GURRAN Departm.nt of Life Sciences The University of the West Indies St Augustine Trinidad and Tobago School of Biology University of St Andrews Fife KY16 9TH Scotland UK

The im.ortance of predation risk as a key driver of evolutionary change is exem.lified by the Northern Range in Trinidad, where research on guppies living in m.ltiple parallel stream. has pro- vided invaluable insights into the process of evolution by natural selection. Although Trinidadian guppies are now a textbook exam.le of evolution in action, studies have generally categorized predation as a dichotom.us variable, representing high or low risk. Yet, ecologists appreciate that com.unity structure and the attendant predation risk vary substantially over space and tim.. Here, we use data from.a longitudinal study of fish assem.lages at 16 different sites in the Northern Range to quantify tem.oral and spatial variation in predation risk. Specifically we ask： 1） Is there evidence for a gradient in predation risk？ 2） Does the ranking of sites （by risk） change with the defi- nition of the predator com.unity （in term. of species com.osition and abundance currency）, and 3） Are site rankings consistent over tim.？ We find com.elling evidence that sites lie along a contin- uum.of risk. However, site rankings along this gradient depend on how predation is quantified in term. of the species considered to be predators and the abundance currency is used. Nonetheless, for a given categorization and currency, rankings are relatively consistent over tim.. Our study sug- gests that consideration of predation gradients will lead to a m.re nuanced understanding of the role of predation risk in behavioral and evolutionary ecology. It also em.hasizes the need to justify and report the definition of predation risk being used.

关键词： abundance currency gradients Poecilia reticulata predation risk Trinidad Trinidadian guppy.

2023年美国麻醉医师学会神经肌肉阻滞监测与拮抗实践指南:美国麻醉医师学会工作组关于神经肌肉阻滞的报告

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中华麻醉学杂志 2024年第5期44卷 518-542页

作者： Stephan R.Thilen Wade A.Weigel m.chael m.todd Richard P.Dutton Cynthia A.Lien Stuart A.Grant Joseph W.Szokol Lars I.Eriksson m.ron Yaster m.rk D.Grant m.dhulika Agarkar Anne m.m.rbella Jaim. F.Blanck Karen B.Dom.no 西雅图华盛顿州明尼阿波里斯明尼苏达州达拉斯得克萨斯州密尔沃基威斯康星州教堂山北卡罗来纳州洛杉矶加利福尼亚州斯德哥尔摩瑞典丹佛科罗拉多州绍姆堡伊利诺斯州巴尔的摩马里兰州

本实践指南基于证据提供了全身麻醉期间及术后神经肌肉功能监测与阻滞拮抗的管理推荐。主要关注神经肌肉功能监测的类型与部位及阻滞拮抗的过程,以减少肌肉松弛药残留阻滞。

关键词：神经肌肉阻滞肌肉松弛药神经肌肉功能监测舒更葡糖钠新斯的明