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Institution

University of Medicine and Dentistry of New Jersey

Education
About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Poison control. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.


Papers
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Journal ArticleDOI
23 Dec 2009-PLOS ONE
TL;DR: 3′UTRs by APA, which result from regulation of both general polyadenylation activity and cell type-specific factors and can reset post-transcriptional gene regulatory programs in the cell, is an integral part of iPS cell generation, and the APA pattern can be a good biomarker for cell type and state, useful for sample classification.
Abstract: Background: The 39 untranslated regions (39UTRs) of mRNAs contain cis elements involved in post-transcriptional regulation of gene expression. Over half of all mammalian genes contain multiple polyadenylation sites that lead to different 39UTRs for a gene. Studies have shown that the alternative polyadenylation (APA) pattern varies across tissues, and is dynamically regulated in proliferating or differentiating cells. Generation of induced pluripotent stem (iPS) cells, in which differentiated cells are reprogrammed to an embryonic stem (ES) cell-like state, has been intensively studied in recent years. However, it is not known how 39UTRs are regulated during cell reprogramming. Methods/Main Findings: Using a computational method that robustly examines APA across DNA microarray data sets, we analyzed 39UTR dynamics in generation of iPS cells from different cell types. We found that 39UTRs shorten during reprogramming of somatic cells, the extent of which depends on the type of source cell. By contrast, reprogramming of spermatogonial cells involves 39UTR lengthening. The alternative polyadenylation sites that are highly responsive to change of cell state in generation of iPS cells are also highly regulated during embryonic development in opposite directions. Compared with other sites, they are more conserved, can lead to longer alternative 39UTRs, and are associated with more cis elements for polyadenylation. Consistently, reprogramming of somatic cells and germ cells involves significant upregulation and downregulation, respectively, of mRNAs encoding polyadenylation factors, and RNA processing is one of the most significantly regulated biological processes during cell reprogramming. Furthermore, genes containing target sites of ES cell-specific microRNAs (miRNAs) in different portions of 39UTR are distinctively regulated during cell reprogramming, suggesting impact of APA on miRNA targeting. Conclusions/Significance: Taken together, these findings indicate that reprogramming of 39UTRs by APA, which result from regulation of both general polyadenylation activity and cell type-specific factors and can reset post-transcriptional gene regulatory programs in the cell, is an integral part of iPS cell generation, and the APA pattern can be a good biomarker for cell type and state, useful for sample classification. The results also suggest that perturbation of the mRNA polyadenylation machinery or RNA processing activity may facilitate generation of iPS cells.

254 citations

Journal ArticleDOI
TL;DR: The NMR-derived structure of the homodimeric core domain of EnvZ that includes His 243, the site of autophosphorylation and phosphate transfer reactions, is presented, revealing the molecular assembly of two active sites within the dimeric kinase.
Abstract: Escherichia coli osmosensor EnvZ is a protein histidine kinase that plays a central role in osmoregulation, a cellular adaptation process involving the His-Asp phosphorelay signal transduction system. Dimerization of the transmembrane protein is essential for its autophosphorylation and phosphorelay signal transduction functions. Here we present the NMR-derived structure of the homodimeric core domain (residues 223–289) of EnvZ that includes His 243, the site of autophosphorylation and phosphate transfer reactions. The structure comprises a four-helix bundle formed by two identical helix-turn-helix subunits, revealing the molecular assembly of two active sites within the dimeric kinase.

254 citations

Journal ArticleDOI
TL;DR: Nampt critically regulates NAD+ and ATP contents, thereby playing an essential role in mediating cell survival by inhibiting apoptosis and stimulating autophagic flux in cardiac myocytes.
Abstract: Rationale: NAD+ acts not only as a cofactor for cellular respiration but also as a substrate for NAD+-dependent enzymes, such as Sirt1. The cellular NAD+ synthesis is regulated by both the de novo and the salvage pathways. Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the salvage pathway. Objective: Here we investigated the role of Nampt in mediating NAD+ synthesis in cardiac myocytes and the function of Nampt in the heart in vivo. Methods and Results: Expression of Nampt in the heart was significantly decreased by ischemia, ischemia/reperfusion and pressure overload. Upregulation of Nampt significantly increased NAD+ and ATP concentrations, whereas downregulation of Nampt significantly decreased them. Downregulation of Nampt increased caspase 3 cleavage, cytochrome c release, and TUNEL-positive cells, which were inhibited in the presence of Bcl-xL, but did not increase hairpin 2–positive cells, suggesting that endogenous Nampt negatively regulates apoptosis but not necrosis....

254 citations

Journal ArticleDOI
TL;DR: It is demonstrated that independent of DNA replication, the TOP1 cleavable complex is ubiquitinated and destroyed in cells treated with antitumor drugs that block the religation step of the Topoisomerase I reaction.

253 citations

Journal ArticleDOI
11 Jun 2004-Science
TL;DR: It is found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin and define a previously unknown function for “linker” histones in gene-specific transcriptional regulation.
Abstract: During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin. Moreover, Msx1 and H1b cooperate to inhibit muscle differentiation in cell culture and in Xenopus animal caps. Our findings define a previously unknown function for "linker" histones in gene-specific transcriptional regulation.

253 citations


Authors

Showing all 14639 results

NameH-indexPapersCitations
John Q. Trojanowski2261467213948
Virginia M.-Y. Lee194993148820
Danny Reinberg14534268201
Michael F. Holick145767107937
Tasuku Honjo14171288428
Arnold J. Levine139485116005
Aaron T. Beck139536170816
Charles J. Yeo13667276424
Jerry W. Shay13363974774
Chung S. Yang12856056265
Paul G. Falkowski12737864898
Csaba Szabó12395861791
William C. Roberts122111755285
Bryan R. Cullen12137150901
John R. Perfect11957352325
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20226
202113
20208
201917
201823
201736