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排序方式: 共有146条查询结果,搜索用时 46 毫秒
51.
Jessica A. Hennessey Nicole J. Boczek Yong-Hui Jiang Joelle D. Miller William Patrick Ryan Pfeiffer Brittan S. Sutphin David J. Tester Hector Barajas-Martinez Michael J. Ackerman Charles Antzelevitch Ronald Kanter Geoffrey S. Pitt 《PloS one》2014,9(9)
Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS), and Timothy syndrome (TS). We identified a variant in CACNA1C in a male child of Filipino descent with arrhythmias and extracardiac features by candidate gene sequencing and performed functional expression studies to electrophysiologically characterize the effects of the variant on CaV1.2 channels. As a baby, the subject developed seizures and displayed developmental delays at 30 months of age. At age 5 years, he displayed a QTc of 520 ms and experienced recurrent VT. Physical exam at 17 years of age was notable for microcephaly, short stature, lower extremity weakness and atrophy with hyperreflexia, spastic diplegia, multiple dental caries and episodes of rhabdomyolysis. Candidate gene sequencing identified a G>C transversion at position 5731 of CACNA1C (rs374528680) predicting a glycine>arginine substitution at residue 1911 (p.G1911R) of CaV1.2. The allele frequency of this variant is 0.01 in Malays, but absent in 984 Caucasian alleles and in the 1000 genomes project. In electrophysiological analyses, the variant decreased voltage-dependent inactivation, thus causing a gain of function of CaV1.2. We also observed a negative shift of V1/2 of activation and positive shift of V1/2 of channel inactivation, resulting in an increase of the window current. Together, these suggest a gain-of-function effect on CaV1.2 and suggest increased susceptibility for arrhythmias in certain clinical settings. The p.G1911R variant was also identified in a case of sudden unexplained infant death (SUID), for which an increasing number of clinical observations have demonstrated can be associated with arrhythmogenic mutations in cardiac ion channels. In summary, the combined effects of the CACNA1C variant to diminish voltage-dependent inactivation of CaV1.2 and increase window current expand our appreciation of mechanisms by which a gain of function of CaV1.2 can contribute to QT prolongation. 相似文献
52.
Background
The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage. 相似文献53.
Esther Heikens Masja Leendertse Lucas M Wijnands Miranda van Luit-Asbroek Marc JM Bonten Tom van der Poll Rob JL Willems 《BMC microbiology》2009,9(1):19-7
Background
Enterococcus faecium has globally emerged as a cause of hospital-acquired infections with high colonization rates in hospitalized patients. The enterococcal surface protein Esp, identified as a potential virulence factor, is specifically linked to nosocomial clonal lineages that are genetically distinct from indigenous E. faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice. 相似文献54.
55.
Pinnacle: a fast, automatic and accurate method for detecting and quantifying protein spots in 2-dimensional gel electrophoresis data 总被引:1,自引:1,他引:0
MOTIVATION: One of the key limitations for proteomic studies using 2-dimensional gel electrophoresis (2DE) is the lack of rapid, robust and reproducible methods for detecting, matching and quantifying protein spots. The most commonly used approaches involve first detecting spots and drawing spot boundaries on individual gels, then matching spots across gels and finally quantifying each spot by calculating normalized spot volumes. This approach is time consuming, error-prone and frequently requires extensive manual editing, which can unintentionally introduce bias into the results. RESULTS: We introduce a new method for spot detection and quantification called Pinnacle that is automatic, quick, sensitive and specific and yields spot quantifications that are reliable and precise. This method incorporates a spot definition that is based on simple, straightforward criteria rather than complex arbitrary definitions, and results in no missing data. Using dilution series for validation, we demonstrate Pinnacle outperformed two well-established 2DE analysis packages, proving to be more accurate and yielding smaller coefficiant of variations (CVs). More accurate quantifications may lead to increased power for detecting differentially expressed spots, an idea supported by the results of our group comparison experiment. Our fast, automatic analysis method makes it feasible to conduct very large 2DE-based proteomic studies that are adequately powered to find important protein expression differences. AVAILABILITY: Matlab code to implement Pinnacle is available from the authors upon request for non-commercial use. 相似文献
56.
Concerted functions of Streptococcus gordonii surface proteins PadA and Hsa mediate activation of human platelets and interactions with extracellular matrix
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Jennifer A. Haworth Howard F. Jenkinson Catherine R. Back Jane L. Brittan Steve W. Kerrigan Angela H. Nobbs 《Cellular microbiology》2017,19(1)
A range of Streptococcus bacteria are able to interact with blood platelets to form a thrombus (clot). Streptococcus gordonii is ubiquitous within the human oral cavity and amongst the common pathogens isolated from subjects with infective endocarditis. Two cell surface proteins, Hsa and Platelet adherence protein A (PadA), in S. gordonii mediate adherence and activation of platelets. In this study, we demonstrate that PadA binds activated platelets and that an NGR (Asparagine‐Glycine‐Arginine) motif within a 657 amino acid residue N‐terminal fragment of PadA is responsible for this, together with two other integrin‐like recognition motifs RGT and AGD. PadA also acts in concert with Hsa to mediate binding of S. gordonii to cellular fibronectin and vitronectin, and to promote formation of biofilms. Evidence is presented that PadA and Hsa are each reliant on the other's active presentation on the bacterial cell surface, suggesting cooperativity in functions impacting both colonization and pathogenesis. 相似文献
57.
58.
59.
Estimating the rate of evolution of the rate of molecular evolution 总被引:35,自引:13,他引:22
A simple model for the evolution of the rate of molecular evolution is
presented. With a Bayesian approach, this model can serve as the basis for
estimating dates of important evolutionary events even in the absence of
the assumption of constant rates among evolutionary lineages. The method
can be used in conjunction with any of the widely used models for
nucleotide substitution or amino acid replacement. It is illustrated by
analyzing a data set of rbcL protein sequences.
相似文献
60.
A simple, fast and sensitive method was developed to verify the presence of
the sialyl Lewis(x) antigen on an N-linked glycoprotein. High performance
liquid chromatography-electrospray mass spectrometry (HPLC-ESI/MS) was used
to identify which of the five N-linked glycosylation sites of human plasma
alpha1-acid-glycoprotein (orosomucoid, OMD) contain the sialyl Lewis(x)
antigen. OMD was digested with proteolytic enzymes and analyzed by reversed
phase chromatography coupled with on-line ESI/MS. A tandem mass
spectrometry experiment was designed to detect the presence of the sialyl
Lewis(x) antigen based on the observation of an 803 mass to charge ratio (
m/z ) ion produced in the intermediate pressure region of the ESI
interface. The ESI/MS signal at m/z 803 is consistent with an oxonium ion
for a glycan structure containing NeuAc, Gal, GlcNAc, and Fuc. The identity
of the m/z 803 ion was confirmed by ESI/MS/MS analysis of the m/z 803
fragment ion and comparison with a sialyl Lewis(x) standard. The
stereochemistry and linkage positions were assigned using previous NMR
analysis but could be determined with permethylation analysis if necessary.
The analysis of OMD gave a pattern showing signal for the sialyl Lewis(x)
antigen coeluting with each of the five N-linked glycopeptides. The ability
to monitor sialyl Lewis(x) expression at each of the five sites is of
interest in the study of OMD's role in inflammatory diseases.
相似文献