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81.
Elucidation of signaling events in a pathogen is potentially important to tackle the infection caused by it. Such events mediated by protein phosphorylation play important roles in infection, and therefore, to predict the phosphosites and substrates of the serine/threonine protein kinases, we have developed a Machine learning-based approach for Mycobacterium tuberculosis serine/threonine protein kinases using kinase-peptide structure–sequence data. This approach utilizes features derived from kinase three-dimensional-structure environment and known phosphosite sequences to generate support vector machine (SVM)-based kinase-specific predictions of phosphosites of serine/threonine protein kinases (STPKs) with no or scarce data of their substrates. SVM outperformed the four machine learning algorithms we tried (random forest, logistic regression, SVM, and k-nearest neighbors) with an area under the curve receiver-operating characteristic value of 0.88 on the independent testing dataset and a 10-fold cross-validation accuracy of ~81.6% for the final model. Our predicted phosphosites of M. tuberculosis STPKs form a useful resource for experimental biologists enabling elucidation of STPK mediated posttranslational regulation of important cellular processes. 相似文献
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83.
Chaperonins are a class of molecular chaperones that assemble into a large double ring architecture with each ring constituting seven to nine subunits and enclosing a cavity for substrate encapsulation. The well-studied Escherichia coli chaperonin GroEL binds non-native substrates and encapsulates them in the cavity thereby sequestering the substrates from unfavorable conditions and allowing the substrates to fold. Using this mechanism, GroEL assists folding of about 10–15 % of cellular proteins. Surprisingly, about 30 % of the bacteria express multiple chaperonin genes. The presence of multiple chaperonins raises questions on whether they increase general chaperoning ability in the cell or have developed specific novel cellular roles. Although the latter view is widely supported, evidence for the former is beginning to appear. Some of these chaperonins can functionally replace GroEL in E. coli and are generally indispensable, while others are ineffective and likewise are dispensable. Additionally, moonlighting functions for several chaperonins have been demonstrated, indicating a functional diversity among the chaperonins. Furthermore, proteomic studies have identified diverse substrate pools for multiple chaperonins. We review the current perception on multiple chaperonins and their physiological and functional specificities. 相似文献
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85.
Entrainment mapping of ischemic ventricular tachycardia at a site in the left ventricle where radiofrequency ablation was successful in terminating the tachycardia revealed a post-pacing interval shorter than the tachycardia cycle length. The reason for the same is explained in the current report. 相似文献
86.
Given the absence of universal marker genes in the viral kingdom, researchers typically use BLAST (with stringent E-values) for taxonomic classification of viral metagenomic sequences. Since majority of metagenomic sequences originate from hitherto unknown viral groups, using stringent e-values results in most sequences remaining unclassified. Furthermore, using less stringent e-values results in a high number of incorrect taxonomic assignments. The SOrt-ITEMS algorithm provides an approach to address the above issues. Based on alignment parameters, SOrt-ITEMS follows an elaborate work-flow for assigning reads originating from hitherto unknown archaeal/bacterial genomes. In SOrt-ITEMS, alignment parameter thresholds were generated by observing patterns of sequence divergence within and across various taxonomic groups belonging to bacterial and archaeal kingdoms. However, many taxonomic groups within the viral kingdom lack a typical Linnean-like taxonomic hierarchy. In this paper, we present ProViDE (Program for Viral Diversity Estimation), an algorithm that uses a customized set of alignment parameter thresholds, specifically suited for viral metagenomic sequences. These thresholds capture the pattern of sequence divergence and the non-uniform taxonomic hierarchy observed within/across various taxonomic groups of the viral kingdom. Validation results indicate that the percentage of 'correct' assignments by ProViDE is around 1.7 to 3 times higher than that by the widely used similarity based method MEGAN. The misclassification rate of ProViDE is around 3 to 19% (as compared to 5 to 42% by MEGAN) indicating significantly better assignment accuracy. ProViDE software and a supplementary file (containing supplementary figures and tables referred to in this article) is available for download from http://metagenomics.atc.tcs.com/binning/ProViDE/ 相似文献
87.
Ciliopathies are pleiotropic and genetically heterogeneous disorders caused by defective development and function of the primary cilium. Bardet-Biedl syndrome (BBS) proteins localize to the base of cilia and undergo intraflagellar transport, and the loss of their functions leads to a multisystemic ciliopathy. Here we report the identification of mutations in guanylate cyclases (GCYs) as modifiers of Caenorhabditis elegans bbs endophenotypes. The loss of GCY-35 or GCY-36 results in suppression of the small body size, developmental delay, and exploration defects exhibited by multiple bbs mutants. Moreover, an effector of cGMP signalling, a cGMP-dependent protein kinase, EGL-4, also modifies bbs mutant defects. We propose that a misregulation of cGMP signalling, which underlies developmental and some behavioural defects of C. elegans bbs mutants, may also contribute to some BBS features in other organisms. 相似文献
88.
Brittain JM Duarte DB Wilson SM Zhu W Ballard C Johnson PL Liu N Xiong W Ripsch MS Wang Y Fehrenbacher JC Fitz SD Khanna M Park CK Schmutzler BS Cheon BM Due MR Brustovetsky T Ashpole NM Hudmon A Meroueh SO Hingtgen CM Brustovetsky N Ji RR Hurley JH Jin X Shekhar A Xu XM Oxford GS Vasko MR White FA Khanna R 《Nature medicine》2011,17(7):822-829
89.
Sethy NK Singh M Kumar R Ilavazhagan G Bhargava K 《Functional & integrative genomics》2011,11(1):119-137
Exposure to high altitude (and thus hypobaric hypoxia) induces electrophysiological, metabolic, and morphological modifications
in the brain leading to several neurological clinical syndromes. Despite the known fact that hypoxia episodes in brain are
a common factor for many neuropathologies, limited information is available on the underlying cellular and molecular mechanisms.
In this study, we investigated the temporal effect of short-term (0–12 h) chronic hypobaric hypoxia on global gene expression
of rat brain followed by detailed canonical pathway analysis and regulatory network identification. Our analysis revealed
significant alteration of 33, 17, 53, 81, and 296 genes (p < 0.05, <1.5-fold) after 0.5, 1, 3, 6, and 12 h of hypoxia, respectively. Biological processes like regulation, metabolic,
and transport pathways are temporally activated along with anti- and proinflammatory signaling networks like PI3K/AKT, NF-κB,
ERK/MAPK, IL-6 and IL-8 signaling. Irrespective of exposure durations, nuclear factor (erythroid-derived 2)-like 2 (NRF2)-mediated oxidative stress response pathway and genes were detected at all time points suggesting activation of NRF2-ARE antioxidant defense system. The results were further validated by assessing the expression levels of selected genes in
temporal as well as brain regions with quantitative RT-PCR and western blot. In conclusion, our whole brain approach with
temporal monitoring of gene expression patterns during hypobaric hypoxia has resulted in (1) deciphering sequence of pathways
and signaling networks activated during onset of hypoxia, and (2) elucidation of NRF2-orchestrated antioxidant response as a major intrinsic defense mechanism. The results of this study will aid in better understanding
and management of hypoxia-induced brain pathologies. 相似文献
90.
Identification of haptoglobin and apolipoprotein A-I as biomarkers for high altitude pulmonary edema
Ahmad Y Shukla D Garg I Sharma NK Saxena S Malhotra VK Bhargava K 《Functional & integrative genomics》2011,11(3):407-417
We have investigated the plasma proteome using 2D gel electrophoresis and matrix-assisted laser desorption/ionization tandem
time of flight from patients with high altitude pulmonary edema (HAPE). A complete proteomic analysis was performed on 20
patients with HAPE and ten healthy sea level controls. In total, we have identified 25 protein spots in human plasma and found
that 14 of them showed altered changes in HAPE patients, which mainly were acute phase proteins (APPs), compliment components,
and apolipoproteins among others. Among the APPs, haptoglobin α2 chain, haptoglobin β chain, transthyretin, and plasma retinol
binding precursor showed overexpression in HAPE patients as compared to controls. To validate the result of proteomic analysis,
two proteins were selected for enzyme-linked immunosorbent assay and Western blotting analysis. Our data conclusively shows
that two proteins, haptoglobin and apolipoprotein A-I are upregulated in plasma of HAPE patients. These proteins may provide
a fast and effective control of inflammatory damage until the subsequent mechanisms can begin to operate. Taken together,
our findings further support the hypothesis that inflammatory response system is linked to the pathophysiology of HAPE. 相似文献