Institution
Kettering University
Education•Flint, Michigan, United States•
About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.
Topics: RNA, Antigen, DNA, Cancer, Population
Papers published on a yearly basis
Papers
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TL;DR: In this paper, a peroxynitrite reductase-peroxidase complex in Mtb was identified, which included products of the genes sucB and lpd, which are annotated to encode the dihydrolipoamide succinyltransferase and lipoamide dehydrogenase (E3) components of α-ketoglutarate deacetyltransferase (KDH).
Abstract: Summary
Mycobacterium tuberculosis (Mtb) persists for prolonged periods in macrophages, where it must adapt to metabolic limitations and oxidative/nitrosative stress. However, little is known about Mtb's intermediary metabolism or antioxidant defences. We recently identified a peroxynitrite reductase-peroxidase complex in Mtb that included products of the genes sucB and lpd, which are annotated to encode the dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) components of α-ketoglutarate dehydrogenase (KDH). However, we could detect no KDH activity in Mtb lysates, nor could we reconstitute KDH by combining the recombinant proteins SucA (annotated as the E1 component of KDH), SucB and Lpd. We therefore renamed the sucB product dihydrolipoamide acyltransferase (DlaT). Mtb lysates contained pyruvate dehydrogenase (PDH) activity, which was lost when the dlaT gene (formerly, sucB) was disrupted. Purification of PDH from Mtb yielded AceE, annotated as an E1 component of PDH, along with DlaT and Lpd. Moreover, anti-DlaT antibody coimmunoprecipitated AceE. Finally, recombinant AceE, DlaT and Lpd, although encoded by genes that are widely separated on the chromosome, reconstituted PDH in vitro with Km values typical of bacterial PDH complexes. In sum, Mtb appears to lack KDH. Instead, DlaT and Lpd join with AceE to constitute PDH.
109 citations
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TL;DR: The finding that the ABD1 gene is required for yeast growth provides the first genetic evidence that a cap methyltransferase (and, by inference, the cap methyl group) plays an essential role in cellular function in vivo.
Abstract: RNA (guanine-7-)methyltransferase, the enzyme responsible for methylating the 5' cap structure of eukaryotic mRNA, was isolated from extracts of Saccharomyces cerevisiae. The yeast enzyme catalyzed methyl group transfer from S-adenosyl-L-methionine to the guanosine base of capped, unmethylated poly(A). Cap methylation was stimulated by low concentrations of salt and was inhibited by S-adenosyl-L-homocysteine, a presumptive product of the reaction, but not by S-adenosyl-D-homocysteine. The methyltransferase sedimented in a glycerol gradient as a single discrete component of 3.2S. A likely candidate for the gene encoding yeast cap methyltransferase was singled out on phylogenetic grounds. The ABD1 gene, located on yeast chromosome II, encodes a 436-amino-acid (50-kDa) polypeptide that displays regional similarity to the catalytic domain of the vaccinia virus cap methyltransferase. That the ABD1 gene product is indeed RNA (guanine-7-)methyltransferase was established by expressing the ABD1 protein in bacteria, purifying the protein to homogeneity, and characterizing the cap methyltransferase activity intrinsic to recombinant ABD1. The physical and biochemical properties of recombinant ABD1 methyltransferase were indistinguishable from those of the cap methyltransferase isolated and partially purified from whole-cell yeast extracts. Our finding that the ABD1 gene is required for yeast growth provides the first genetic evidence that a cap methyltransferase (and, by inference, the cap methyl group) plays an essential role in cellular function in vivo.
109 citations
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TL;DR: A ventral midbrain precursor map is defined based on the timing of Gli1 and Shh expression, and suggests that the diversity of midbrain dopaminergic neurons is at least partially determined during their precursor stage when their medial-lateral position, differential gene expression and the time when they leave the ventricular zone influence their fate decisions.
Abstract: Background
The ventral midbrain contains a diverse array of neurons, including dopaminergic neurons of the ventral tegmental area (VTA) and substantia nigra (SN) and neurons of the red nucleus (RN). Dopaminergic and RN neurons have been shown to arise from ventral mesencephalic precursors that express Sonic Hedgehog (Shh). However, Shh expression, which is initially confined to the mesencephalic ventral midline, expands laterally and is then downregulated in the ventral midline. In contrast, expression of the Hedgehog target gene Gli1 initiates in the ventral midline prior to Shh expression, but after the onset of Shh expression it is expressed in precursors lateral to Shh-positive cells. Given these dynamic gene expression patterns, Shh and Gli1 expression could delineate different progenitor populations at distinct embryonic time points.
109 citations
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TL;DR: The MSK-MET dataset as discussed by the authors is an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types.
Abstract: Progression to metastatic disease remains the main cause of cancer death. Yet, the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we present MSK-MET, an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients. We analyzed this dataset to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metastatic burden in some tumor types, including prostate adenocarcinoma, lung adenocarcinoma and HR-positive breast ductal carcinoma, but not in others, such as colorectal adenocarcinoma, pancreatic adenocarcinoma and high-grade serous ovarian cancer. We also identified specific somatic alterations associated with increased metastatic burden and specific routes of metastatic spread. Our data offer a unique resource for the investigation of the biological basis for metastatic spread and highlight the crucial role of chromosomal instability in cancer progression.
108 citations
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TL;DR: In this paper, the development of T lymphocytes in 34 patients engrafted with allogeneic bone marrow was studied by indirect immunofluorescence using mouse monoclonal antibodies.
108 citations
Authors
Showing all 6853 results
Name | H-index | Papers | Citations |
---|---|---|---|
Joan Massagué | 189 | 408 | 149951 |
Chris Sander | 178 | 713 | 233287 |
Timothy A. Springer | 167 | 669 | 122421 |
Murray F. Brennan | 161 | 925 | 97087 |
Charles M. Rice | 154 | 561 | 83812 |
Lloyd J. Old | 152 | 775 | 101377 |
Howard I. Scher | 151 | 944 | 101737 |
Paul Tempst | 148 | 309 | 89225 |
Pier Paolo Pandolfi | 146 | 529 | 88334 |
Barton F. Haynes | 144 | 911 | 79014 |
Jedd D. Wolchok | 140 | 713 | 123336 |
James P. Allison | 137 | 483 | 83336 |
Harold E. Varmus | 137 | 496 | 76320 |
Scott W. Lowe | 134 | 396 | 89376 |
David S. Klimstra | 133 | 564 | 61682 |