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41.
Cinco RM Robblee JH Messinger J Fernandez C McFarlane Holman KL Sauer K Yachandra VK 《Biochemistry》2004,43(42):13271-13282
The oxygen-evolving complex of photosystem II (PS II) in green plants and algae contains a cluster of four Mn atoms in the active site, which catalyzes the photoinduced oxidation of water to dioxygen. Along with Mn, calcium and chloride ions are necessary cofactors for proper functioning of the complex. The current study using polarized Sr EXAFS on oriented Sr-reactivated samples shows that Fourier peak II, which fits best to Mn at 3.5 A rather than lighter atoms (C, N, O, or Cl), is dichroic, with a larger magnitude at 10 degrees (angle between the PS II membrane normal and the X-ray electric field vector) and a smaller magnitude at 80 degrees . Analysis of the dichroism of the Sr EXAFS yields a lower and upper limit of 0 degrees and 23 degrees for the average angle between the Sr-Mn vectors and the membrane normal and an isotropic coordination number (number of Mn neighbors to Sr) of 1 or 2 for these layered PS II samples. The results confirm the contention that Ca (Sr) is proximal to the Mn cluster and lead to refined working models of the heteronuclear Mn(4)Ca cluster of the oxygen-evolving complex in PS II. 相似文献
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Yano J Kern J Pushkar Y Sauer K Glatzel P Bergmann U Messinger J Zouni A Yachandra VK 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1494):1139-47; discussion 1147
The application of high-resolution X-ray spectroscopy methods to study the photosynthetic water oxidizing complex, which contains a unique hetero-nuclear catalytic Mn4Ca cluster, is described. Issues of X-ray damage, especially at the metal sites in the Mn4Ca cluster, are discussed. The structure of the Mn4Ca catalyst at high resolution, which has so far eluded attempts of determination by X-ray diffraction, X-ray absorption fine structure (EXAFS) and other spectroscopic techniques, has been addressed using polarized EXAFS techniques applied to oriented photosystem II (PSII) membrane preparations and PSII single crystals. A review of how the resolution of traditional EXAFS techniques can be improved, using methods such as range-extended EXAFS, is presented, and the changes that occur in the structure of the cluster as it advances through the catalytic cycle are described. X-ray absorption and emission techniques (XANES and Kbeta emission) have been used earlier to determine the oxidation states of the Mn4Ca cluster, and in this report we review the use of X-ray resonant Raman spectroscopy to understand the electronic structure of the Mn4Ca cluster as it cycles through the intermediate S-states. 相似文献
44.
Zinc half sites are present in all human lactogenic hormones: human prolactin (hPRL), growth hormone (hGH), placental lactogens (hPL) and the hPRL receptor (hPRLr). The influence of divalent zinc (Zn(2+)) as measured by intrinsic fluorescence or FRET in each of these hormones is unique and is affected by the presence of varying stoichiometries of hPRLr. These data show that both Zn(2+) and hPRLr binding influence hPRL conformers in an interdependent fashion. Although each of these three lactogenic hormones bind hPRLr and induce a biological response that is sensitive to the presence of increasing concentrations of Zn(2+), each hormone is unique in the mechanistic details of this process. 相似文献
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Shantanu K. Kar Binod Sah Bikash Patnaik Yang Hee Kim Anna S. Kerketta Sunheang Shin Shyam Bandhu Rath Mohammad Ali Vittal Mogasale Hemant K. Khuntia Anuj Bhattachan Young Ae You Mahesh K. Puri Anna Lena Lopez Brian Maskery Gopinath B. Nair John D. Clemens Thomas F. Wierzba 《PLoS neglected tropical diseases》2014,8(2)
Introduction
The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.Methods
All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.Results
The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.Discussion
This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem. 相似文献47.
Trivedi RK Layek B Kumar TS Vittal S Ganneboina R Dubey PK Mullangi R Srinivas NR 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,860(2):227-234
A highly sensitive and enantioselective assay has been developed and validated for the estimation of torcetrapib (TTB) enantiomers [(+)-TTB and (-)-TTB] in hamster plasma with chiral liquid chromatography coupled to tandem mass spectrometry with an atmospheric pressure chemical ionization interface in the negative-ion mode. The assay procedure involves liquid-liquid extraction of TTB enantiomers and IS (DRL-16126) from 100 microL hamster plasma with acetonitrile. TTB enantiomers were separated using n-hexane:propanol (80:20, v/v) at a flow rate of 0.7 mL/min on a Chiralpak AD column. The MS/MS ion transitions monitored were 599.2-->340.2 for TTB and 623.2-->298.1 for IS. Absolute recovery was found to be between 64 and 68% for TTB enantiomers and >100% for IS. The standard curves for TTB enantiomers were linear (r(2)>0.995) in the concentration range 5-2500 ng/mL for each enantiomer with an LLOQ of 5 ng/mL for each enantiomer. The inter- and intra-day precisions were in the range of 10.5-12.4 and 9.15-11.5% and 3.75-12.9 and 5.16-12.5% for (+)-TTB and (-)-TTB, respectively. Accuracy in the measurement of quality control (QC) samples was in the range 91.3-105 and 88.6-111% for (+)-TTB and (-)-TTB, respectively. This novel method has been applied to the study of stereoselective oral pharmacokinetics of (-)-TTB. 相似文献
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Kondalarao Bankapalli SreeDivya Saladi Sahezeel S. Awadia Arvind Vittal Goswami Madhuja Samaddar Patrick D'Silva 《The Journal of biological chemistry》2015,290(44):26491-26507
Methylglyoxal (MG) is a reactive metabolic intermediate generated during various
cellular biochemical reactions, including glycolysis. The accumulation of MG
indiscriminately modifies proteins, including important cellular antioxidant
machinery, leading to severe oxidative stress, which is implicated in multiple
neurodegenerative disorders, aging, and cardiac disorders. Although cells
possess efficient glyoxalase systems for detoxification, their functions are
largely dependent on the glutathione cofactor, the availability of which is
self-limiting under oxidative stress. Thus, higher organisms require alternate
modes of reducing the MG-mediated toxicity and maintaining redox balance. In
this report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpI
family in Saccharomyces cerevisiae, plays an indispensable role
in regulating redox homeostasis. Our results show that Hsp31 possesses robust
glutathione-independent methylglyoxalase activity and suppresses MG-mediated
toxicity and ROS levels as compared with another paralog, Hsp34. On the other
hand, glyoxalase-defective mutants of Hsp31 were found highly compromised in
regulating the ROS levels. Additionally, Hsp31 maintains cellular glutathione
and NADPH levels, thus conferring protection against oxidative stress, and Hsp31
relocalizes to mitochondria to provide cytoprotection to the organelle under
oxidative stress conditions. Importantly, human DJ-1, which is implicated in the
familial form of Parkinson disease, complements the function of Hsp31 by
suppressing methylglyoxal and oxidative stress, thus signifying the importance
of these proteins in the maintenance of ROS homeostasis across phylogeny. 相似文献
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Juang YC Landry MC Sanches M Vittal V Leung CC Ceccarelli DF Mateo AR Pruneda JN Mao DY Szilard RK Orlicky S Munro M Brzovic PS Klevit RE Sicheri F Durocher D 《Molecular cell》2012,45(3):384-397
Highlights? Identification of OTUB1 mutants with impaired ability to inhibit E2 enzymes ? Crystal structure of a ubiquitin-charged E2 bound to OTUB1 ? Molecular basis of Lys48-linked ubiquitin chain recognition by OTUB1 determined ? OTUB1 employs product inhibition mimicry to inhibit E2 enzymes 相似文献
50.
Thampi P Rao HV Mitter SK Cai J Mao H Li H Seo S Qi X Lewin AS Romano C Boulton ME 《PloS one》2012,7(4):e34468
Age-related macular degeneration (AMD), a major cause of blindness in the elderly, is associated with oxidative stress, lipofuscin accumulation and retinal degeneration. The aim of this study was to determine if a 5-HT(1A) receptor agonist can reduce lipofuscin accumulation, reduce oxidative damage and prevent retinal cell loss both in vitro and in vivo. Autophagy-derived and photoreceptor outer segment (POS)-derived lipofuscin formation was assessed using FACS analysis and confocal microscopy in cultured retinal pigment epithelial (RPE) cells in the presence or absence of the 5-HT(1A) receptor agonist, 8-OH DPAT. 8-OH DPAT treatment resulted in a dose-dependent reduction in both autophagy- and POS-derived lipofuscin compared to control. Reduction in autophagy-induced lipofuscin was sustained for 4 weeks following removal of the drug. The ability of 8-OH DPAT to reduce oxidative damage following exposure to 200 μM H(2)O(2) was assessed. 8-OH DPAT reduced superoxide generation and increased mitochondrial superoxide dismutase (MnSOD) levels and the ratio of reduced glutathione to the oxidized form of glutathione in H(2)O(2)-treated cells compared to controls and protected against H(2)O(2)-initiated lipid peroxidation, nitrotyrosine levels and mitochondrial damage. SOD2 knockdown mice, which have an AMD-like phenotype, received daily subcutaneous injections of either saline, 0.5 or 5.0 mg/kg 8-OH DPAT and were evaluated at monthly intervals. Systemic administration of 8-OH DPAT improved the electroretinogram response in SOD2 knockdown eyes of mice compared to knockdown eyes receiving vehicle control. There was a significant increase in the ONL thickness in mice treated with 8-OH DPAT at 4 months past the time of MnSOD knockdown compared to untreated controls together with a 60% reduction in RPE lipofuscin. The data indicate that 5-HT(1A) agonists can reduce lipofuscin accumulation and protect the retina from oxidative damage and mitochondrial dysfunction. 5-HT(1A) receptor agonists may have potential as therapeutic agents in the treatment of retinal degenerative disease. 相似文献