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991.
M. Keith Wyatt Jen-Yue Tsai Sanghamitra Mishra Maria Campos Cynthia Jaworski Robert N. Fariss Steven L. Bernstein Graeme Wistow 《PloS one》2013,8(6)
Age-related macular degeneration (AMD) is a major cause of vision loss. It is associated with development of characteristic plaque-like deposits (soft drusen) in Bruch’s membrane basal to the retinal pigment epithelium (RPE). A sequence variant (Y402H) in short consensus repeat domain 7 (SCR7) of complement factor H (CFH) is associated with risk for “dry” AMD. We asked whether the eye-targeting of this disease might be related to specific interactions of CFH SCR7 with proteins expressed in the aging human RPE/choroid that could contribute to protein deposition in drusen. Yeast 2-hybrid (Y2H) screens of a retinal pigment epithelium/choroid library derived from aged donors using CFH SCR7 baits detected an interaction with EFEMP1/Fibulin 3 (Fib3), which is the locus for an inherited macular degeneration and also accumulates basal to macular RPE in AMD. The CFH/Fib3 interaction was validated by co-immunoprecipitation of native proteins. Quantitative Y2H and ELISA assays with different recombinant protein constructs both demonstrated higher affinity for Fib3 for the disease-related CFH 402H variant. Immuno-labeling revealed colocalization of CFH and Fib3 in globular deposits within cholesterol-rich domains in soft drusen in two AMD donors homozygous for CFH 402H (H/H). This pattern of labeling was quite distinct from those seen in examples of eyes with Y/Y and H/Y genotypes. The CFH 402H/Fib3 interaction could contribute to the development of pathological aggregates in soft drusen in some patients and as such might provide a target for therapeutic intervention in some forms of AMD. 相似文献
992.
993.
Population indices of bacteria and archaea were investigated from saline–alkaline soil and a possible microbe–environment pattern was established using gene targeted metagenomics. Clone libraries were constructed using 16S rRNA and functional gene(s) involved in carbon fixation (cbbL), nitrogen fixation (nifH), ammonia oxidation (amoA) and sulfur metabolism (apsA). Molecular phylogeny revealed the dominance of Actinobacteria, Firmicutes and Proteobacteria along with archaeal members of Halobacteraceae. The library consisted of novel bacterial (20%) and archaeal (38%) genera showing ≤95% similarity to previously retrieved sequences. Phylogenetic analysis indicated ability of inhabitant to survive in stress condition. The 16S rRNA gene libraries contained novel gene sequences and were distantly homologous with cultured bacteria. Functional gene libraries were found unique and most of the clones were distantly related to Proteobacteria, while clones of nifH gene library also showed homology with Cyanobacteria and Firmicutes. Quantitative real-time PCR exhibited that bacterial abundance was two orders of magnitude higher than archaeal. The gene(s) quantification indicated the size of the functional guilds harboring relevant key genes. The study provides insights on microbial ecology and different metabolic interactions occurring in saline–alkaline soil, possessing phylogenetically diverse groups of bacteria and archaea, which may be explored further for gene cataloging and metabolic profiling. 相似文献
994.
Paras Kumar Mishra Srikanth Givvimani Vishalakshi Chavali Suresh C. Tyagi 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2271-2276
Cardiac muscle is unique because it contracts ceaselessly throughout the life and is highly resistant to fatigue. The marvelous nature of the cardiac muscle is attributed to its matrix that maintains structural and functional integrity and provides ambient micro-environment required for mechanical, cellular and molecular activities in the heart. Cardiac matrix dictates the endothelium myocyte (EM) coupling and contractility of cardiomyocytes. The matrix metalloproteinases (MMPs) and their tissue inhibitor of metalloproteinases (TIMPs) regulate matrix degradation that determines cardiac fibrosis and myocardial performance. We have shown that MMP-9 regulates differential expression of micro RNAs (miRNAs), calcium cycling and contractility of cardiomyocytes. The differential expression of miRNAs is associated with angiogenesis, hypertrophy and fibrosis in the heart. MMP-9, which is involved in the degradation of cardiac matrix and induction of fibrosis, is also implicated in inhibition of survival and differentiation of cardiac stem cells (CSC). Cardiac matrix is distinct because it renders mechanical properties and provides a framework essential for differentiation of cardiac progenitor cells (CPC) into specific lineage. Cardiac matrix regulates myocyte contractility by EM coupling and calcium transients and also directs miRNAs required for precise regulation of continuous and synchronized beating of cardiomyocytes that is indispensible for survival. Alteration in the matrix homeostasis due to induction of MMPs, altered expression of specific miRNAs or impaired signaling for contractility of cardiomyocytes leads to catastrophic effects. This review describes the mechanisms by which cardiac matrix regulates myocardial performance and suggests future directions for the development of treatment strategies in cardiovascular diseases. 相似文献
995.
996.
Ashish Fauzdar Mohit Chowdhry R. N. Makroo Manoj Mishra Priyanka Srivastava Richa Tyagi Preeti Bhadauria Anita Kaul 《Indian journal of human genetics》2013,19(1):32-42
BACKGROUND AND OBJECTIVE:
Women with high-risk pregnancies are offered prenatal diagnosis through amniocentesis for cytogenetic analysis of fetal cells. The aim of this study was to evaluate the effectiveness of the rapid fluorescence in situ hybridization (FISH) technique for detecting numerical aberrations of chromosomes 13, 21, 18, X and Y in high-risk pregnancies in an Indian scenario.MATERIALS AND METHODS:
A total of 163 samples were received for a FISH and/or a full karyotype for prenatal diagnosis from high-risk pregnancies. In 116 samples both conventional culture techniques for getting karyotype through G-banding techniques were applied in conjunction to FISH test using the AneuVysion kit (Abbott Molecular, Inc.), following standard recommended protocol to compare the both the techniques in our setup.RESULTS:
Out of 116 patients, we got 96 normal for the five major chromosome abnormality and seven patients were found to be abnormal (04 trisomy 21, 02 monosomy X, and 01 trisomy 13) and all the FISH results correlated with conventional cytogenetics. To summarize the results of total 163 patients for the major chromosomal abnormalities analyzed by both/or cytogenetics and FISH there were 140 (86%) normal, 9 (6%) cases were abnormal and another 4 (2.5%) cases were suspicious mosaic and 10 (6%) cases of culture failure. The diagnostic detection rate with FISH in 116 patients was 97.5%. There were no false-positive and false-negative autosomal or sex chromosomal results, within our established criteria for reporting FISH signals.CONCLUSION:
Rapid FISH is a reliable and prompt method for detecting numerical chromosomal aberrations and has now been implemented as a routine diagnostic procedure for detection of fetal aneuploidy in India. 相似文献997.
998.
999.
Saxena Amrita Mishra Sandhya Ray Shatrupa Raghuwanshi Richa Singh Harikesh Bahadur 《Journal of Plant Growth Regulation》2020,39(2):751-763
Journal of Plant Growth Regulation - Induction of defense response in host plants by the Trichoderma spp. has been attributed as one of the major mechanisms leading to inhibition of the pathogenic... 相似文献
1000.
Sumeet Patiyal Piyush Agrawal Vinod Kumar Anjali Dhall Rajesh Kumar Gaurav Mishra Gajendra P.S. Raghava 《Protein science : a publication of the Protein Society》2020,29(1):201-210
N‐acetylglucosamine (NAG) belongs to the eight essential saccharides that are required to maintain the optimal health and precise functioning of systems ranging from bacteria to human. In the present study, we have developed a method, NAGbinder, which predicts the NAG‐interacting residues in a protein from its primary sequence information. We extracted 231 NAG‐interacting nonredundant protein chains from Protein Data Bank, where no two sequences share more than 40% sequence identity. All prediction models were trained, validated, and evaluated on these 231 protein chains. At first, prediction models were developed on balanced data consisting of 1,335 NAG‐interacting and noninteracting residues, using various window size. The model developed by implementing Random Forest using binary profiles as the main principle for identifying NAG‐interacting residue with window size 9, performed best among other models. It achieved highest Matthews Correlation Coefficient (MCC) of 0.31 and 0.25, and Area Under Receiver Operating Curve (AUROC) of 0.73 and 0.70 on training and validation data set, respectively. We also developed prediction models on realistic data set (1,335 NAG‐interacting and 47,198 noninteracting residues) using the same principle, where the model achieved MCC of 0.26 and 0.27, and AUROC of 0.70 and 0.71, on training and validation data set, respectively. The success of our method can be appraised by the fact that, if a sequence of 1,000 amino acids is analyzed with our approach, 10 residues will be predicted as NAG‐interacting, out of which five are correct. Best models were incorporated in the standalone version and in the webserver available at https://webs.iiitd.edu.in/raghava/nagbinder/ 相似文献