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91.
92.
The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the
major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006
of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as
the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug
(MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The
diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of
specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced
immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in
remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping
drug toxicities, risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic
point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients
who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control
programs, in India. 相似文献
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95.
Performance of inverse anaerobic fluidized bed reactor for treating high strength organic wastewater during start-up phase 总被引:2,自引:0,他引:2
The aim of this work is to report on the physical characteristics of carrier material (perlite), biomass growth on the carrier material and the biogas production during an apparent steady state period in an inverse anaerobic fluidized bed reactor (IAFBR) for treating high strength organic wastewater. Before starting up the reactor, physical properties of the carrier material were determined. One millimeter diameter perlite particle is found to have a wet specific density of 295 kg/m(3) with specific surface area of 7.010 m(2)/g. This material has provided a good surface for biomass attachment and development. The biofilm concentration (in terms of attached volatile solids (AVS)) attached to carrier material was found to be 0.66 g(AVS)/g(solid). Most particles have been covered with a thin biofilm of uniform thickness. Once the inverse anaerobic fluidized bed system reached the steady state, the organic load was increased step wise by reducing hydraulic retention time (HRT) from 2 days to 0.16 day, while maintaining the constant feed of chemical oxygen demand (COD) concentration. This system has achieved 84% COD removal and reached the biogas production of 13.22 l/l/d at an organic loading rate (OLR) of 35 kgCOD/m(3)/d. 相似文献
96.
Saccharomyces cerevisiae expresses a 67.8 kDa homodimeric serine thioesterase, S-formylglutathione hydrolase (SFGH), that is 39.9% identical with human esterase D. Both enzymes possess significant carboxylesterase and S-formylglutathione thioesterase activity but are unusually resistant to organophosphate (OP) inhibitors. We determined the X-ray crystal structure of yeast (y) SFGH to 2.3 A resolution by multiwavelength anomalous dispersion and used the structure to guide site-specific mutagenesis experiments addressing substrate and inhibitor reactivity. Our results demonstrate a steric mechanism of OP resistance mediated by a single indole ring (W197) located in an enzyme "acyl pocket". The W197I substitution enhances ySFGH reactivity with paraoxon by >1000-fold ( k i (W197I) = 16 +/- 2 mM (-1) h (-1)), thereby overcoming natural OP resistance. W197I increases the rate of OP inhibition under pseudo-first-order conditions but does not accelerate OP hydrolysis. The structure of the paraoxon-inhibited W197I variant was determined by molecular replacement (2.2 A); it revealed a stabilized sulfenic acid at Cys60. Wild-type (WT) ySFGH is inhibited by thiol reactive compounds and is sensitive to oxidation; thus, the cysteine sulfenic acid may play a role in the regulation of a "D-type" esterase. The structure of the W197I variant is the first reported cysteine sulfenic acid in a serine esterase. We constructed five Cys60/W197I variants and show that introducing a positive charge near the oxyanion hole, W197I/C60R or W197I/C60K, results in a further enhancement of the rates of phosphorylation with paraoxon ( k i = 42 or 80 mM (-1) h (-1), respectively) but does not affect the dephosphorylation of the enzyme. We also characterized three histidine substitutions near the oxyanion hole, G57H, L58H, and M162H, which significantly decrease esterase activity. 相似文献
97.
Imidazolonepropionase (HutI) (imidazolone-5-propanote hydrolase, EC 3.5.2.7) is a member of the amidohydrolase superfamily and catalyzes the conversion of imidazolone-5-propanoate to N-formimino-L-glutamate in the histidine degradation pathway. We have determined the three-dimensional crystal structures of HutI from Agrobacterium tumefaciens (At-HutI) and an environmental sample from the Sargasso Sea Ocean Going Survey (Es-HutI) bound to the product [ N-formimino-L-glutamate (NIG)] and an inhibitor [3-(2,5-dioxoimidazolidin-4-yl)propionic acid (DIP)], respectively. In both structures, the active site is contained within each monomer, and its organization displays the landmark feature of the amidohydrolase superfamily, showing a metal ligand (iron), four histidines, and one aspartic acid. A catalytic mechanism involving His265 is proposed on the basis of the inhibitor-bound structure. This mechanism is applicable to all HutI forms. 相似文献
98.
Brca2 (XRCC11) Deficiency Results in Radioresistant DNA Synthesis and a Higher Frequency of Spontaneous Deletions 总被引:1,自引:0,他引:1 下载免费PDF全文
Maria Kraakman-van der Zwet Wilhelmina J. I. Overkamp Rebecca E. E. van Lange Jeroen Essers Annemarie van Duijn-Goedhart Ingrid Wiggers Srividya Swaminathan Paul P. W. van Buul Abdellatif Errami Raoul T. L. Tan Nicolaas G. J. Jaspers Shyam K. Sharan Roland Kanaar Magorzata Z. Zdzienicka 《Molecular and cellular biology》2002,22(2):669-679
We show here that the radiosensitive Chinese hamster cell mutant (V-C8) of group XRCC11 is defective in the breast cancer susceptibility gene Brca2. The very complex phenotype of V-C8 cells is complemented by a single human chromosome 13 providing the BRCA2 gene, as well as by the murine Brca2 gene. The Brca2 deficiency in V-C8 cells causes hypersensitivity to various DNA-damaging agents with an extreme sensitivity toward interstrand DNA cross-linking agents. Furthermore, V-C8 cells show radioresistant DNA synthesis after ionizing radiation, suggesting that Brca2 deficiency affects cell cycle checkpoint regulation. In addition, V-C8 cells display tremendous chromosomal instability and a high frequency of abnormal centrosomes. The mutation spectrum at the hprt locus showed that the majority of spontaneous mutations in V-C8 cells are deletions, in contrast to wild-type V79 cells. A mechanistic explanation for the genome instability phenotype of Brca2-deficient cells is provided by the observation that the nuclear localization of the central DNA repair protein in homologous recombination, Rad51, is reduced in V-C8 cells. 相似文献
99.
Swaminathan Palanisami Krishna Kannan Uma Lakshmanan 《Journal of applied phycology》2012,24(5):1093-1098
The marine cyanobacterium Phormidium valderianum BDU 140441 exhibited the ability to grow at 0.25?mM tannic acid, a known hindering chemical for microbial growth. The tannic acid-degrading ability of the organism is evident from the UV–visible absorption spectrum. In addition, the existence of tannase has been localized by activity staining, and its induction in activity upon tannic acid exposure was confirmed in native gel. The critical tannic acid metabolization enzymes tested for are polyphenol oxidase and esterases; both are well known for tannic acid degradation. Upon tannic acid exposure, increased activity of polyphenol oxidase and expression of few new isoforms of esterase were identified by activity staining. 相似文献
100.
Yifeng Tao Ashok Rajaraman Xiaoyue Cui Ziyi Cui Haoran Chen Yuanqi Zhao Jesse Eaton Hannah Kim Jian Ma Russell Schwartz 《PLoS computational biology》2021,17(3)
Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, which act in different combinations or degrees in different cancers. These variations in mutability phenotypes are predictive of progression outcomes independent of the specific mutations they have produced to date. Here we explore the question of how and to what degree these differences in mutational phenotypes act in a cancer to predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational phenotypes, followed by a machine learning framework to identify key features predictive of progression. Analyses of breast invasive carcinoma and lung carcinoma demonstrate that a large fraction of the risk of future clinical outcomes of cancer progression—overall survival and disease-free survival—can be explained solely from mutational phenotype features derived from the phylogenetic analysis. We further show that mutational phenotypes have additional predictive power even after accounting for traditional clinical and driver gene-centric genomic predictors of progression. These results confirm the importance of mutational phenotypes in contributing to cancer progression risk and suggest strategies for enhancing the predictive power of conventional clinical data or driver-centric biomarkers. 相似文献