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Ferreras, Julian A.,Stirrett, Karen L.,Lu, Xuequan,Ryu, Jae-Sang,Soll, Clifford E.,Tan, Derek S.,Quadri, Luis E.N. 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.18
Phenolic glycolipids (PGLs) are polyketide-derived virulence factors produced by Mycobacterium tuber-culosis, M. leprae, and other mycobacterial pathogens. We have combined bioinformatic, genetic, biochemical, and chemical biology approaches to illuminate the mechanism of chain initiation required for assembly of the p-hydroxyphenyl-polyketide moiety of PGLs. Our studies have led to the identification of a stand-alone, didomain initiation module, FadD22, comprised of a p-hydroxybenzoic acid adenylation domain and an aroyl carrier protein domain. FadD22 forms an acyl-S-enzyme covalent intermediate in the p-hydroxyphenyl-polyketide chain assembly line. We also used this information to develop a small-molecule inhibitor of PGL biosynthesis. Overall, these studies provide insights into the biosynthesis of an important group of small-molecule mycobacterial virulence factors and support the feasibility of targeting PGL biosynthesis to develop new drugs to treat mycobacterial infections.
Julian A Ferreras,Ryu, Jae-Sang,Federico Di Lello,Derek S Tan,Luis E N Quadri 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.16
Mycobacterium tuverculosis and Yersinia pestis, the causative agents of tuberculosis and plague respectively are pathogens with serious ongoing impact on global public health^(1,2) and potential use as agents of bioterrorism^(3). Both pathogens have iron acquisition systems based on siderphores secreted iron-chelating compounds with extremey high Fe^(3+)affinity(4,5) Several lines of evidence suggest that siderophores have a critical role in bacterial iron acquisition inside the human host^(6-9) where the free iron concentration is well bellow that required for bacterial growth and virulence ^(10) Thus, siderophore biosynthesis is an attractive target in the development of new antibiotics to treat tuberculosis and plague^(2,5,8,11). In particular, such drugs alone or as part of combination therapies could provide a valuable new line of defense against intractable muliple-drug-resistant infections Here we report the design synthesis and domain salicylation enzymes required for siderophore biosynthesis siderophore biosynthesis and growth of M. tuberculosis and Y, pestis under iron-limiting conditions.
Decoding the spectra of SDSS early-type galaxies: new indicators of age and recent star formation
Rogers, Ben,Ferreras, Ignacio,Lahav, Ofer,Bernardi, Mariangela,Kaviraj, Sugata,Yi, Sukyoung K. Blackwell Publishing Ltd 2007 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.382 No.2
<P>ABSTRACT</P><P>We apply principal component analysis (PCA) to a sample of early-type galaxies from the Sloan Digital Sky Survey (SDSS) in order to infer differences in their star formation histories from their unresolved stellar populations. We select a <I>z</I> < 0.1 volume-limited sample comprising ∼7000 early-type galaxies from SDSS/Data Release 4. Out of the first few principal components (PC), we study four which give information about stellar populations and velocity dispersion. We construct two parameters (η and ζ) as linear combinations of PC1 and PC2. The four components can be presented as ‘optimal filters’ to explore in detail the properties of the underlying stellar populations. By comparing various photospectroscopic observables – including near-ultraviolet (NUV) photometry from Galaxy Evolution Explorer (GALEX) – we find ζ to be most sensitive to recent episodes of star formation, and η to be strongly dependent on the average age of the stellar populations. Both η and ζ also depend on metallicity. We apply these optimal filters to composite spectra assembled by Bernardi et al. The distribution of the η component of the composites appear to be indistinguishable between high- and low-density regions, whereas the distribution of ζ parameters have a significant skew towards lower values for galaxies in low-density regions. This result suggests that galaxies in lower density environments are less likely to present weak episodes of recent star formation. In contrast, a significant number of galaxies from our high-density subsample – which includes clusters (both outer regions and centres) and groups – underwent small but detectable recent star formation at high metallicity, in agreement with recent estimates targeting elliptical galaxies in Hickson Compact Groups and in the field.</P>
Bi, Qifang,Ferreras, Eva,Pezzoli, Lorenzo,Legros, Dominique,Ivers, Louise C,Date, Kashmira,Qadri, Firdausi,Digilio, Laura,Sack, David A,Ali, Mohammad,Lessler, Justin,Luquero, Francisco J,Azman, Andrew Elsevier Science ;, The Lancet Pub. Group 2017 LANCET INFECTIOUS DISEASES Vol.17 No.10
<P><B>Summary</B></P><P><B>Background</B></P><P>Killed whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature.</P><P><B>Methods</B></P><P>For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232.</P><P><B>Findings</B></P><P>Seven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, <I>I</I><SUP>2</SUP>=58%) and effectiveness of 76% (62–85, <I>I</I><SUP>2</SUP>=0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15–42], <I>I</I><SUP>2</SUP>=0%) was lower than in those 5 years or older (64% [58–70], <I>I</I><SUP>2</SUP>=0%; p<0·0001). Two-dose efficacy estimates of kOCV were similar during the first 2 years after vaccination, with estimates of 56% (95% CI 42–66, <I>I</I><SUP>2</SUP>=45%) in the first year and 59% (49–67, <I>I</I><SUP>2</SUP>=0) in the second year. The efficacy reduced to 39% (13 to 57, <I>I</I><SUP>2</SUP>=48%) in the third year, and 26% (−46 to 63, <I>I</I><SUP>2</SUP>=74%) in the fourth year.</P><P><B>Interpretation</B></P><P>Two kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control.</P><P><B>Funding</B></P><P>The Bill & Melinda Gates Foundation.</P>