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Christopher E. Heise Jeremy Murray Katherine E. Augustyn Brandon Bravo Preeti Chugha Frederick Cohen Anthony M. Giannetti Paul Gibbons Rami N. Hannoush Brian R. Hearn Priyadarshini Jaishankar Cuong Q. Ly Kinjalkumar Shah Karen Stanger Micah Steffek Yinyan Tang Xianrui Zhao Joseph W. Lewcock Adam R. Renslo John Flygare Michelle R. Arkin 《PloS one》2012,7(12)
Inhibition of caspase-6 is a potential therapeutic strategy for some neurodegenerative diseases, but it has been difficult to develop selective inhibitors against caspases. We report the discovery and characterization of a potent inhibitor of caspase-6 that acts by an uncompetitive binding mode that is an unprecedented mechanism of inhibition against this target class. Biochemical assays demonstrate that, while exquisitely selective for caspase-6 over caspase-3 and -7, the compound’s inhibitory activity is also dependent on the amino acid sequence and P1’ character of the peptide substrate. The crystal structure of the ternary complex of caspase-6, substrate-mimetic and an 11 nM inhibitor reveals the molecular basis of inhibition. The general strategy to develop uncompetitive inhibitors together with the unique mechanism described herein provides a rationale for engineering caspase selectivity. 相似文献
23.
Le MT Wertheim HF Nguyen HD Taylor W Hoang PV Vuong CD Nguyen HL Nguyen HH Nguyen TQ Nguyen TV Van TD Ngoc BT Bui TN Nguyen BG Nguyen LT Luong ST Phan PH Pham HV Nguyen T Fox A Nguyen CV Do HQ Crusat M Farrar J Nguyen HT de Jong MD Horby P 《PloS one》2008,3(10):e3339
Background
Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.Methods and Findings
Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.Conclusion
In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended. 相似文献24.
A rare new species of Sapindus from Vietnam, Sapindus sonlaensis, is described, illustrated, and compared to similar species. 相似文献
25.
Nguyen Huy Thuan Amit Kumar Chaudhary Duong Van Cuong Nguyen Xuan Cuong 《Journal of industrial microbiology & biotechnology》2018,45(3):175-185
Microbial cells have extensively been utilized to produce value-added bioactive compounds. Based on advancement in protein engineering, DNA recombinant technology, genome engineering, and metabolic remodeling, the microbes can be re-engineered to produce industrially and medicinally important platform chemicals. The emergence of co-culture system which reduces the metabolic burden and allows parallel optimization of the engineered pathway in a modular fashion restricting the formation of undesired byproducts has become an alternative way to synthesize and produce bioactive compounds. In this study, we present genetically engineered E. coli-based co-culture system to the de novo synthesis of apigetrin (APG), an apigenin-7-O-β-d-glucopyranoside of apigenin. The culture system consists of an upstream module including 4-coumarate: CoA ligase (4CL), chalcone synthase, chalcone flavanone isomerase (CHS, CHI), and flavone synthase I (FNSI) to synthesize apigenin (API) from p-coumaric acid (PCA). Whereas, the downstream system contains a metabolizing module to enhance the production of UDP-glucose and expression of glycosyltransferase (PaGT3) to convert API into APG. To accomplish this improvement in titer, the initial inoculum ratio of strains for making the co-culture system, temperature, and media component was optimized. Following large-scale production, a yield of 38.5 µM (16.6 mg/L) of APG was achieved. In overall, this study provided an efficient tool to synthesize bioactive compounds in microbial cells. 相似文献
26.
Ferdinand Bohlmann Ngo Le Van Thi Van Cuong Pham Jasmin Jacupovic Angelica Schuster Volker Zabel William H. Watson 《Phytochemistry》1979,18(11):1831-1834
The investigation of several Berkheya species afforded in addition to already known compounds three unusual sesquiterpene hydrocarbons. Together with modhephene and isocomene, a new one is present, its structure being elucidated by spectroscopic methods and by some chemical transformations. All 18 species investigated contain the typical thiophene derivatives, isolated earlier; the patterns of compounds present divide the species into two groups. 相似文献
27.
Strong and stable geographic differentiation of swamp buffalo maternal and paternal lineages indicates domestication in the China/Indochina border region 总被引:2,自引:0,他引:2
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Yi Zhang Yongfang Lu Marnoch Yindee Kuan‐Yi Li Hsiao‐Yun Kuo Yu‐Ten Ju Shaohui Ye Md Omar Faruque Qiang Li Yachun Wang Vu Chi Cuong Lan Doan Pham Bounthong Bouahom Bingzhuang Yang Xianwei Liang Zhihua Cai Dianne Vankan Wallaya Manatchaiworakul Nonglid Kowlim Somphot Duangchantrasiri Worawidh Wajjwalku Ben Colenbrander Yuan Zhang Peter Beerli Johannes A. Lenstra J. Stuart F. Barker 《Molecular ecology》2016,25(7):1530-1550
The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y‐chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y‐chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock. 相似文献
28.
Cuong Quang Le Mercy Oyugi Ebenezer Joseph Toan Nguyen Md Hasmat Ullah Joshua Aubert Thien Phan Joseph Tran Kayunta Johnson-Winters 《Biochemistry and Biophysics Reports》2017
F420H2:NADP+ Oxidoreductase (Fno) catalyzes the reversible reduction of NADP+ to NADPH by transferring a hydride from the reduced F420 cofactor. Here, we have employed binding studies, steady-state and pre steady-state kinetic methods upon wtFno and isoleucine 135 (I135) Fno variants in order to study the effects of side chain length on the donor-acceptor distance between NADP+ and the F420 precursor, FO. The conserved I135 residue of Fno was converted to a valine, alanine and glycine, thereby shortening the side chain length. The steady-state kinetic analysis of wtFno and the variants showed classic Michaelis-Menten kinetics with varying FO concentrations. The data revealed a decreased kcat as side chain length decreased, with varying FO concentrations. The steady-state plots revealed non-Michaelis-Menten kinetic behavior when NADPH was varied. The double reciprocal plot of the varying NADPH concentrations displays a downward concave shape, while the NADPH binding curves gave Hill coefficients of less than 1. These data suggest that negative cooperativity occurs between the two identical monomers. The pre steady-state Abs420 versus time trace revealed biphasic kinetics, with a fast phase (hydride transfer) and a slow phase. The fast phase displayed an increased rate constant as side chain length decreased. The rate constant for the second phase, remained ~2 s?1 for each variant. Our data suggest that I135 plays a key role in sustaining the donor-acceptor distance between the two cofactors, thereby regulating the rate at which the hydride is transferred from FOH2 to NADP+. Therefore, Fno is a dynamic enzyme that regulates NADPH production. 相似文献
29.
Background
Inference of protein interaction networks from various sources of data has become an important topic of both systems and computational biology. Here we present a supervised approach to identification of gene expression regulatory networks. 相似文献30.
Mark Hamann Chu The Cuong Nguyen Duy Hong Pham Thuoc Bui Thi Thuhien 《Biodiversity and Conservation》2006,15(11):3703-3720
To establish baseline data on the distribution, abundance and threats to marine turtles in Viet Nam we conducted surveys with
local fishers, community members and provincial Ministry of Fisheries staff from 17 of Viet Nam’s 29 coastal provinces. These
data indicate that five species of marine turtle reside in Viet Nam’s waters (loggerhead, olive ridley, leatherback, green
and hawksbill turtles), and four species nest on Viet Nam’s beaches (all of the above except the loggerhead turtle). It is
evident from these data that significant declines have occurred in both foraging and nesting populations of all five marine
turtle species found in Viet Nam. The greatest current threats to marine turtle populations in Viet Nam are habitat degradation,
the accidental and opportunistic of turtles capture by fishers and the direct take of nesting females and their eggs. Successful
conservation efforts have been made in recent years through collaboration between international Non Government Organisations
and several Vietnamese Government Ministries. Continued success of these projects and the development and implementation of
marine conservation policy will depend upon building awareness among Government employees, fishers and the general public
about marine turtle biology, ecology, and the need to protect them. 相似文献