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1Boceprevir,GC-376,and calpain inhibitors Ⅱ,Ⅻ inhibit SARS-CoV-2 viral replication by targeting the viral main protease显示文摘A new coronavirus SARS-CoV-2,also called novel coronavirus 2019(2019-nCoV),started to circulate among humans around December 2019,and it is now widespread as a global pandemic.The disease caused by SARS-CoV-2 virus is called COVID-19,which is highly contagious and has an overall mortality rate of 6.35%as of May 26,2020.There is no vaccine or antiviral available for SARS-CoV-2.In this study,we report our discovery of inhibitors targeting the SARS-CoV-2 main protease(Mpro).Using the FRET-based enzymatic assay,several inhibitors including boceprevir,GC-376,and calpain inhibitorsⅡ,andⅫwere identified to have potent activity with single-digit to submicromolar ICs0 values in the enzymatic assay.The mechanism of action of the hits was further characterized using enzyme kinetic studies,thermal shift binding assays,and native mass spectrometry.Significantly,four compounds(boceprevir,GC-376,calpain inhibitorsⅡandⅫ)inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37μM.Notably,boceprevir,calpain inhibitorsⅡandⅫrepresent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors.A complex crystal structure of SARS-CoV-2 Mpro with GC-376,determined at 2.15(A)resolution with three protomers per asymmetric unit,revealed two unique binding configurations,shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro.Overall,the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.Chunlong Ma Michael Dominic Sacco Brett Hurst Julia Alma Townsend Yanmei Hu Tommy Szeto Xiujun Zhang Bart Tarbet Michael Thomas Marty Yu Chen Jun Wang 2020Cell Research2020,30,8:13
2Polycondensation reaction and its mechanism during lignocellulosic liquefaction by an acid catalyst: a review显示文摘The increase in the residue content resulting from polycondensation would be adverse to the utilization of lignocellulose and to the quality of products obtained from liquefied lignocellulosic material.The yield of the residue formed from liquefaction and the mechanism of polycondensation were reported mainly by Lin,Yamada and Kobayashi.The major products of cellulosic liquefaction are levulinic acid and hydroxymethylfurfural(HMF) derivatives under polyhydric alcohols and phenolated compounds under phenols.The cleavage of the β-O-4 bonds is the major reaction pathway of lignin liquefaction under various liquefying reagents regardless of whether they contain acid catalysts or not.The break up compounds by decomposition are polymerized to substances with high molecular weight by polycondensation in lignocellulosic liquefaction.The molecular weight of condensed residues increases almost linearly as a function of liquefaction time at the later stage of lignocellulosic liquefaction.The longer the time required,the greater the content of new residue generated by polycondensation during the entire process of liquefaction.We conclude that the condensed residues may stem from the interaction of degraded lignin and cellulose components in wood or from the products of two major components reacting with liquefying reagents.NIU Min ZHAO Guang-jie Mehmet Hakki ALMA 2011Forestry Studies in China2011,13,1:7
3saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription显示文摘Victoria Portnoy Szu Hua Sharon Lin Kathy H Li Alma Burlingame Zheng-Hui Hu Hao Li Long-Cheng Li 2016Cell Research2016,26,3:6
4Proteomics Analysis Reveals Post-Translational Mechanisms for Cold-Induced Metabolic Changes in Arabidopsis显示文摘基因表示和新陈代谢的导致寒冷的变化是批评的让植物幸存结冰。主要由改变基因表示,到不会结冻的低温度的一个时期的暴露增加植物忍耐到作为冷环境适应知道的 freezinga 现象。在在结冰下面的温度落下指以前,寒冷也导致快速的新陈代谢的变化,它提供立刻的保护。为对寒冷的如此的快速的新陈代谢的回答的分子的机制仍然保持大部分未知。这里,我们使用 Arabidopsis thaliana proteome 的亚 cellular 部分的分析结合了的二维的差别胶化电气泳动(2-D DIGE ) 由双人脚踏车团 spectrometry 看到鉴定在 Arabidopsis 识别早寒冷应答的蛋白质。这些蛋白质包括涉及淀粉降级,三 HSP100 蛋白质,在 tricarboxylic 酸周期的几蛋白质,和蔗糖新陈代谢的四酶。在冷处理之上, Disproportionating 酶 2 (DPE2 ) ,使麦芽糖产生代射变化到葡萄糖的 cytosolic transglucosidase,在 centrifugation 小团部分很快增加了并且在可溶的部分减少了。与 DPE2 酶的活动的导致寒冷的 inactivation 一致,没有影响 C 重复有约束力的抄写因素(CBF ) , dpe2 异种显示出增加的结冰忍耐 transcriptional 小径。这些结果支持一个模型那导致寒冷的 inactivation DPE2 导致麦芽糖的快速的累积,它是保护房间免受结冰的伤害的导致寒冷的兼容溶质损坏。这研究为在对突然的温度的植物保护的新陈代谢的酶掉的糖类的快速的 translational 以后规定的一个关键角色提供证据。Tian Li Shou-Ling XU Juan A. Oses-Prieto Sunita Putil Peng Xu Rui-Ju Wang Kathy H. Li David A. Maltby Liz-He An Alma L. Burlingame Zhi-Ping Deng Zhi-Yong Wang 2011Molecular Plant2011,4,2:6
5Authors and Open Access:Effective Ways to Achieve OA in China显示文摘Although there are effective methods available to authors for providing open access to their work, more than half are still not doing so and provision in China is poorer than in many other countries. There are a number of issues and concerns that dissuade authors from making their work open access: some are still unaware of the concept and of the increased visibility and impact that open access brings; many are unfamiliar with open access journals and how they work; many are uninformed about self-archiving and for some of those who are aware of the possibility of providing open access by this means, concerns about copyright and technical issues remain.Yet all these worries can be addressed with simple facts that reassure and encourage authors to adopt open access to benefit themselves,their research and their teaching. There is also a wealth of resources now available to authors that provide information and advice on open access and its effects. As institutions and research funders, both with a strong interest in maximising the visibility and impact of research they support, begin to develop formal policies on open access, models for its provision are emerging. The optimal model is a frills' variant) or by service providers who add functionality or selectivity to provide users with value-enhanced products.Alma Swan 2005图书情报工作2005,49,12:5
6The Arabidopsis B-box protein BZS1/BBX20 interacts with HY5 and mediates strigolactone regulation of photomorphogenesis显示文摘Plant growth is controlled by integration of hormonal and light-signaling pathways. BZS1 is a B-box zinc finger protein previously characterized as a negative regulator in the brassinosteroid(BR)-signaling pathway and a positive regulator in the light-signaling pathway. However, the mechanisms by which BZS1/BBX20 integrates light and hormonal pathways are not fully understood. Here, using a quantitative proteomic workflow, we identified several BZS1-associated proteins, including light-signaling components COP1 and HY5. Direct interactions of BZS1 with COP1 and HY5 were verified by yeast two-hybrid and co-immunoprecipitation assays. Overexpression of BZS1 causes a dwarf phenotype that is suppressed by the hy5 mutation, while overexpression of BZS1 fused with the SRDX transcription repressor domain(BZS1-SRDX) causes a long-hypocotyl phenotype similar to hy5, indicating that BZS1's function requires HY5. BZS1 positively regulates HY5 expression, whereas HY5 negatively regulates BZS1 protein level, forming a feedback loop that potentially contributes to signaling dynamics. In contrast to BR,strigolactone(SL) increases BZS1 level, whereas the SL responses of hypocotyl elongation, chlorophyll and HY5 accumulation are diminished in the BZS1-SRDX seedlings, indicating that BZS1 is involved in these SL responses. These results demonstrate that BZS1 interacts with HY5 and plays a central role in integrating light and multiple hormone signals for photomorphogenesis in Arabidopsis.Chuang-Qi Wei Chih-Wei Chien Lian-Feng Ai Jun Zhao Zhenzhen Zhang Kathy H. Li Alma L. Burlingame Yu Sun Zhi-Yong Wang 2016Journal of Genetics and Genomics2016,43,9:5
7The Brassinosteroid-Activated BRI1 Receptor Kinase Is Switched off by Dephosphorylation Mediated by Cytoplasm-Localized PP2A B' Subunits显示文摘Brassinosteroid (BR ) 绑定由与它的合作受体 kinase BAK1 导致 heterodimerization 激活受体 kinase BRI1;然而, reversibly 使 BRI1 失去活性的机制仍然保持不清楚。这里,我们证明细胞质局部性的蛋白质磷酸酶 2A (PP2A ) B′regulatory 子单元与 BRI1 交往调停它的 dephosphorylation 和 inactivation。Loss-of-function 和 overexpression 实验显示出那一组 PP2A B′regulatory 子单元,由 B′ 代表了,否定地调整由减少的 BRI1 phosphorylation 发信号的 BR。BR 增加这些 B′subunits,和 B′ 的表示层次与 phosphorylated BRI1 优先地交往,建议 BR 发信号的动力学被 BRI1 的调停 PP2A 的反馈 inactivation 调制。与 PP2A B′ 相比并且 B′ ,它由 dephosphorylating 支持 BR 回答下游的抄写因素 BZR1,使 BRI1 失去活性 B′subunits 显示出类似的绑定到 BRI1 和 BZR1 但是不同 subcellular 本地化。B′subunits 的原子 / 细胞质的本地化的改变揭示了那细胞质的 PP2A dephosphorylates BRI1 并且禁止 BR 反应,而原子 PP2A dephosphorylates BZR1 并且激活 BR 反应。我们的调查结果不仅识别调停的 PP2A 规章的 B 子单元 BRI1 的绑定和 dephosphorylation,而且证明 PP2A 的 subcellular 本地化在 BR 发信号上指定它的底层选择和不同效果。Ruiju Wang Mengmeng Liu Min Yuan Juan A. Oses-Prieto Xingbo Cai Ying Sun Alma L. Burlingame Zhi-Yong Wang Wenqiang Tang 2016Molecular Plant2016,9,1:5
8Proteomic Study Identifies Proteins Involved in Brassinosteroid Regulation of Rice Growth显示文摘Brassinosteroids (BRs) are essential hormones for growth and development of plant. In rice, BRs regulate multiple developmental processes and affect many important traits such as height, leaf angle, fertility and seed filling. We identified brassinosteroid-regulated proteins in rice using proteomic approaches and performed functional analysis of some BR-regulated proteins by overexpression experiments. Using two-dimensional difference gel electrophoresis (2-D DIGE) followed by protein identification by mass spectrometry, we compared proteomic differences in the shoots and roots of the BR-insensitive mutant d61-4 and BR-deficient mutant brd1-3. We identified a large number of proteins differentially expressed in the mutants compared with wild type control. These include a glycine-rich RNA-binding protein (OsGRP1) and a DREPP2 protein, which showed reduced levels in the BR mutants. Overexpression of these two proteins partially suppressed the dwarf phenotype of the Arabidopsis BR-insensitive mutant bri1-5. In contrast to the reduced protein level, the RNA level of OsGRP1 was not significantly affected in the BR mutants or by BR treatment, suggesting BR regulation of OsGRP1 at the posttranslational level. This study identifies many BR-regulated proteins and demonstrates that OsGRP1 functions downstream in the BR signal transduction pathway to promote cell expansion.Fengru Wang Ming-Yi Bai Zhiping Deng Juan A. Oses-Prieto Alma L. Burlingame Tiegang Lu Kang Chong Zhi-Yong Wang 2010Journal of Integrative Plant Biology2010,52,12:4
9Hepatitis B virus infection in Latin America:A genomic medicine approach显示文摘Hepatitis B virus(HBV)infection is the leading cause of severe chronic liver disease.This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America.Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection.Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America;these strains have historically circulated among the indigenous population.Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans.In contrast,genotypes F,A and D are common in acute and chronic infections among mestizos with Caucasian ancestry.Hepatocellular carcinoma is rare in Mexicans,but it has been associated with genotype F1b among Argentineans.This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America,which contrast with those reported in other regions of the world.Sonia Roman Alexis Jose-Abrego Nora Alma Fierro Griselda Escobedo-Melendez Claudia Ojeda-Granados Erika Martinez-Lopez Arturo Puro 2014World Journal of Gastroenterology2014,20,23:4
10开放获取机构知识库:强制性存储政策显示文摘全世界所有学科中共有约24000种同行评议期刊,这些期刊每年出版研究论文的约有2亿5千万篇。尽管宣传开放获取的益处使得人们对开放获取的了解有所增加,出版界也逐渐开始进行开放获取实验,但目前只有15%的论文通过作者自愿进行自存储而实现了开放获取(Open Access,即自由地联机获取)。Les Carr(著) Alma Swan(著) 李麟(编译) 2006图书情报工作动态2006,,9:3
11Melatonin modifies SOX2^+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation显示文摘Melatonin is a pleiotropic molecule that,after a short-term sleep deprivation,promotes the proliferation of neural stem cells in the adult hippocampus.However,this effect has not been observed in long-term sleep deprivation.The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated,but evidence indicates that epigenetic regulators may be involved in this process.In this study,we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization.Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus.We observed that let-7 b,mir-132,and mir-124 were highly expressed in the dentate gyrus after melatonin administration,but they were not modified by sleep deprivation.In addition,we found more Sox2^+/5-bromo-2’-deoxyuridine(BrdU)^+cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group.These findings may support the notion that melatonin modifies the expression of epigenetic mediators that,in turn,regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions.All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara,Mexico(approval No.CI-16610)on January 2,2016.Alan Hinojosa-Godínez Luis F. Jave-Suarez Mario Flores-Soto Alma Y. Gálvez-Contreras Sonia Luquín Edith Oregon-Romero Oscar González-Pérez Rocio E. González-Castaneda 2019Neural Regeneration Research2019,14,10:2
12开放获取发展史大事记显示文摘2007年是开放获取在政策制订和实践推动方面发展迅速的一年。在2007年即将结束的时候,开放获取事业又向前迈出了一步,美国国会将NIH的强制性开放获取政策纳入08年财政拨款法案,意味着如果美国总统批准,该政策将成为法律。此外,越来越多的国家、政府部门、研究机构和资助机构制订并开始实施强制性的开放获取政策,这与最初鼓励性的软性建议相比,无疑具有更积极的意义。 本期我们组织了开放获取专题,集中报道近一段时间来,国际开放获取事业的发展。Alma Swan推出了她一年一度的开放获取主题的台历,今年的主题是开放获取发展史回顾;eIFL今年的开放获取会议在香港举办,视角聚焦在开放获取知识库的建设;从研究人员到信息服务机构都在倡议、呼吁强制性的开放获取政策,甚至针对出版商的抵制活动直接行动起来以行动和对策相回应;在制订开放获取政策的同时,政策制订者们开始考虑与政策相配套的机制的建立,如专职的开放获取办公室、开放获取专员等等。Alma Swan(汇编) 刘兰(编译) 黄国彬(编译) 孙巍(编译) 李麟(校) 2007图书情报工作动态2007,,10:2
13Oral hygiene practices,smoking habit,and self-perceived oral malodor among dental students显示文摘Almas K Al-Hawish A Al-Khamis W 2003J Contemp Dent Pract2003,4,4:2
14Value of Symptoms to Predict Tilt Testing Outcome in Patients with Clinical Suspicion of Vasovagal Syncope显示文摘Maite Vallejo Antonio G. Hermosillo Manlio F. Márquez Alma K. Urquidez Arturo Sotomayor Elizabeth Salas Manuel Cárdenas 2007Archives of Medical Research2007,,5:2
15Influence of catalytic systems on process of model object hydrogenation显示文摘On the basis of b-FeOOH,Fe(OA)_(3),Fe_(3)O_(4) iron and spherical catalysts NiO/SiO_(2),Fe_(2)O_(3)/SiO_(2) derived from slag waste coals of heating electrical stations,the hydrogenation of model polycyclic hydrocarbon at presence of nanodimensioned catalysts antracene was studied.On the example of conversion of anthracene,it was shown that upon release of hydrogenation of the product yield and degradation of polycyclic hydrocarbons in the hydrogenation,the mentioned catalyst systems appeared to be in the following order:nanoparticles b-FeOOH,Fe(OA)_(3) and Fe_(3)O_(4)[spherical catalysts NiO/SiO_(2),Fe_(2)O_(3)/SiO_(2)[commercial cobalt-molybdenum catalyst.The results showed that the catalysts studied are promising catalysts for the hydrogenation of polycyclic hydrocarbons and may be used for direct coal liquefaction.Murzabek Ispolovich Baikenov Gulzhan Gausilevna Baikenova Bolat Shaimenovich Sarsembayev Alma Baimagambetova Tateeva Almas Tusipkhan Aisha Zharasovna Matayeva 2014International Journal of Coal Science & Technology2014,1,1:2
16Control of free AA levels by phospholipases A2 and lysophospholipid acyltransferases 显示文摘GEMA P C ALMA M A DAVID B 2009Biochim Biophys Acta2009,1791,12:1
17Copper(II) removal from aqueous solution by organosolv lignin and its recovery显示文摘Acemioglu B Samil A Alma M H Gundogan R 2003Appl Polymer Sci2003,89,:1
18The knowledge and practices of oral hygiene methods and attendance pattern among school teachers in Riyadh, Saudi Arabia显示文摘Almas K Al-Malik TM AI-Shehri MA 2003Saudi Med J2003,24,10:1
19Effect of credit guar- antee policy on survival andperformanee of SMEs in Republic of Ko- rea显示文摘Jae Kang Almas Heshmati 2008 2008Small Business Economics2008,31,4:1
20SNP discovery in the bovine milk transcriptome using RNA-Seq technology显示文摘Angela Cánovas Gonzalo Rincon Alma Islas-Trejo Saumya Wickramasinghe Juan F. Medrano 2010Mammalian Genome2010,,11:1
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