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We performed polymerase chain reaction analysis of 8 restriction-site polymorphisms in the beta-globin gene cluster to define haplotypes and provide hematological profiles of Relli and Thurpu Kapu caste populations in Andhra Pradesh, India. In all sickle cell homozygous subjects, the clinical manifestation of the disease is benign with elevated fetal hemoglobin levels (3.9%-21.1%). Clinical symptoms in some of the sickle cell homozygous subjects include jaundice, leg ulcers, and splenomegaly. Molecular analysis of the sickle cell gene (HBB*S) reveals the presence of the ubiquitous Arab-Indian haplotype in both populations. We encountered, for the first time, a rare, atypical haplotype ((+)-------) in a sickle cell homozygous individual of the Thurpu Kapu population, presumably the result of gene conversion. 相似文献
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Aflaki E Radovic B Chandak PG Kolb D Eisenberg T Ring J Fertschai I Uellen A Wolinski H Kohlwein SD Zechner R Levak-Frank S Sattler W Graier WF Malli R Madeo F Kratky D 《The Journal of biological chemistry》2011,286(9):7418-7428
Programmed cell death of lipid-laden macrophages is a prominent feature of atherosclerotic lesions and mostly ascribed to accumulation of excess intracellular cholesterol. The present in vitro study investigated whether intracellular triacylglycerol (TG) accumulation could activate a similar apoptotic response in macrophages. To address this question, we utilized peritoneal macrophages isolated from mice lacking adipose triglyceride lipase (ATGL), the major enzyme responsible for TG hydrolysis in multiple tissues. In Atgl(-/-) macrophages, we observed elevated levels of cytosolic Ca(2+) and reactive oxygen species, stimulated cytochrome c release, and nuclear localization of apoptosis-inducing factor. Fragmented mitochondria prior to cell death were indicative of the mitochondrial apoptosis pathway being triggered as a consequence of defective lipolysis. Other typical markers of apoptosis, such as externalization of phosphatidylserine in the plasma membrane, caspase 3 and poly(ADP-ribose) polymerase cleavage, were increased in Atgl(-/-) macrophages. An artificial increase of cellular TG levels by incubating wild-type macrophages with very low density lipoprotein closely mimicked the apoptotic phenotype observed in Atgl(-/-) macrophages. Results obtained during the present study define a novel pathway linking intracellular TG accumulation to mitochondrial dysfunction and programmed cell death in macrophages. 相似文献
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High resolution methylome map of rat indicates role of intragenic DNA methylation in identification of coding region 总被引:1,自引:0,他引:1
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Ian PG Marshall Dusty RV Berggren Mohammad F Azizian Luke C Burow Lewis Semprini Alfred M Spormann 《The ISME journal》2012,6(4):814-826
We developed a broad-ranging method for identifying key hydrogen-producing and consuming microorganisms through analysis of hydrogenase gene content and expression in complex anaerobic microbial communities. The method is based on a tiling hydrogenase gene oligonucleotide DNA microarray (Hydrogenase Chip), which implements a high number of probes per gene by tiling probe sequences across genes of interest at 1.67 × –2 × coverage. This design favors the avoidance of false positive gene identification in samples of DNA or RNA extracted from complex microbial communities. We applied this technique to interrogate interspecies hydrogen transfer in complex communities in (i) lab-scale reductive dehalogenating microcosms enabling us to delineate key H2-consuming microorganisms, and (ii) hydrogen-generating microbial mats where we found evidence for significant H2 production by cyanobacteria. Independent quantitative PCR analysis on selected hydrogenase genes showed that this Hydrogenase Chip technique is semiquantitative. We also determined that as microbial community complexity increases, specificity must be traded for sensitivity in analyzing data from tiling DNA microarrays. 相似文献
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Ensemble docking has provided an inexpensive method to account for receptor flexibility in molecular docking for virtual screening. Unfortunately, as there is no rigorous theory to connect the docking scores from multiple structures to measured activity, researchers have not yet come up with effective ways to use these scores to classify compounds into actives and inactives. This shortcoming has led to the decrease, rather than an increase in the performance of classifying compounds when more structures are added to the ensemble. Previously, we suggested machine learning, implemented in the form of a naïve Bayesian model could alleviate this problem. However, the naïve Bayesian model assumed that the probabilities of observing the docking scores to different structures to be independent. This approximation might prevent it from achieving even higher performance. In the work presented in this paper, we have relaxed this approximation when using several other machine learning methods—k nearest neighbor, logistic regression, support vector machine, and random forest—to improve ensemble docking. We found significant improvement. 相似文献
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Glauber P Arêas R?de BB Schuab Felipe PG Neves Rosana R Barros 《Memórias do Instituto Oswaldo Cruz》2014,109(7):935-939
Streptococcus pyogenes is responsible for a variety of infectious
diseases and immunological complications. In this study, 91 isolates of S.
pyogenes recovered from oropharynx secretions were submitted to
antimicrobial susceptibility testing, emm typing and pulsed-field
gel electrophoresis (PFGE) analysis. All isolates were susceptible to ceftriaxone,
levofloxacin, penicillin G and vancomycin. Resistance to erythromycin and clindamycin
was 15.4%, which is higher than previous reports from this area, while 20.9% of the
isolates were not susceptible to tetracycline. The macrolide resistance phenotypes
were cMLSB (10) and iMLSB (4). The ermB gene was predominant,
followed by the ermA gene. Thirty-two emm types and
subtypes were found, but five (emm1, emm4,
emm12, emm22, emm81) were detected in
48% of the isolates. Three new emm subtypes were identified
(emm1.74, emm58.14, emm76.7).
There was a strong association between emm type and PFGE clustering.
A variety of PFGE profiles as well as emm types were found among
tetracycline and erythromycin-resistant isolates, demonstrating that antimicrobial
resistant strains do not result from the expansion of one or a few clones. This study
provides epidemiological data that contribute to the development of suitable
strategies for the prevention and treatment of such infections in a poorly studied
area. 相似文献
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Kosala GAD Weerakoon Senanayake AM Kularatne Deepthika H Edussuriya Sarachchandra KA Kodikara Laxman PG Gunatilake Vasanti G Pinto Ashoka B Seneviratne Sunethra Gunasena 《BMC research notes》2011,4(1):268