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941.
We extend the continuity of microblade technology in the Indian Subcontinent to 45 ka, on the basis of optical dating of microblade assemblages from the site of Mehtakheri, (22° 13'' 44″ N Lat 76° 01'' 36″ E Long) in Madhya Pradesh, India. Microblade technology in the Indian Subcontinent is continuously present from its first appearance until the Iron Age (~3 ka), making its association with modern humans undisputed. It has been suggested that microblade technology in the Indian Subcontinent was developed locally by modern humans after 35 ka. The dates reported here from Mehtakheri show this inference to be untenable and suggest alternatively that this technology arrived in the Indian Subcontinent with the earliest modern humans. It also shows that modern humans in Indian Subcontinent and SE Asia were associated with differing technologies and this calls into question the “southern dispersal” route of modern humans from Africa through India to SE Asia and then to Australia. We suggest that modern humans dispersed from Africa in two stages coinciding with the warmer interglacial conditions of MIS 5 and MIS 3. Competitive interactions between African modern humans and Indian archaics who shared an adaptation to tropical environments differed from that between modern humans and archaics like Neanderthals and Denisovans, who were adapted to temperate environments. Thus, while modern humans expanded into temperate regions during warmer climates, their expansion into tropical regions, like the Indian Subcontinent, in competition with similarly adapted populations, occurred during arid climates. Thus modern humans probably entered the Indian Subcontinent during the arid climate of MIS 4 coinciding with their disappearance from the Middle East and Northern Africa. The out of phase expansion of modern humans into tropical versus temperate regions has been one of the factors affecting the dispersal of modern humans from Africa during the period 200–40 ka. 相似文献
942.
Hemant Bengani Shweta Mendiratta Jayant Maini Dasari Vasanthi Hina Sultana Mohsen Ghasemi Jasmine Ahluwalia Sowmya Ramachandran Rakesh K. Mishra Vani Brahmachari 《PloS one》2013,8(6)
Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans. The cis-acting elements interacting with these proteins, however, are poorly understood in mammals. In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene. It down regulates reporter gene expression in HEK cells and the repression is dependent on polycomb group of proteins (PcG). We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively. In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE. Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins. 相似文献
943.
Vivek Mishra Rachel Cline Pawan Noel Jenny Karlsson Catherine J. Baty Lidiya Orlichenko Krutika Patel Ram Narayan Trivedi Sohail Z. Husain Chathur Acharya Chandra Durgampudi Donna B. Stolz Sarah Navina Vijay P. Singh 《PloS one》2013,8(6)
Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. 相似文献
944.
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
945.
946.
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
947.
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
948.
Dominique P Frueh Andrew C Goodrich Subrata H Mishra Scott R Nichols 《Current opinion in structural biology》2013,23(5):734-739
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949.
Chandrabhan Seniya Harshal Mishra Ajay Yadav Nitin Sagar Babita Chaturvedi Kuldeep Uchadia Gulshan Wadhwa 《Bioinformation》2013,9(1):54-60
4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological
activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is
essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in
Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme''s activity to
meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV
GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein
was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK.
The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper.
Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for
NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski''s rule of 5
using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two Hbonds
(Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of
51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient
profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV
infections using NS2B Site 2 as a Drug target. 相似文献
950.
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