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Phillip A. Sharp

Bio: Phillip A. Sharp is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: RNA & RNA splicing. The author has an hindex of 172, co-authored 614 publications receiving 117126 citations. Previous affiliations of Phillip A. Sharp include McGovern Institute for Brain Research & Medical Research Council.
Topics: RNA, RNA splicing, Gene, Transcription (biology), DNA


Papers
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Journal ArticleDOI
23 Jun 1971-Nature
TL;DR: In selecting for covalently circular R factor DNA molecules, the procedures used in these earlier experiments-caesium chloride-ethidium bromide centrifuga-tion7 and bulk nitrocellulose adsorption2—necessarily selected against isolation of other (non-circular) forms of R factorDNA that might have been present.
Abstract: STUDIES1–6 of the molecular nature of antibiotic resistance (R) factors in Escherichia coli have shown that several of them consist of covalently closed molecules of circular DNA. Use was made of this property in the separation of the R factor from chromosomal DNA of E. coli, which has a similar nucleotide-base composition. In selecting for covalently circular R factor DNA molecules, however, the procedures used in these earlier experiments-caesium chloride-ethidium bromide centrifuga-tion7 and bulk nitrocellulose adsorption2—necessarily selected against isolation of other (non-circular) forms of R factor DNA that might have been present.

24 citations

Journal ArticleDOI
TL;DR: Surprisingly, infection of cells pretreated with the protein synthesis inhibitor cycloheximide stimulated the synthesis of about 10-fold-higher levels of early viral mRNA's than did comparable infections of nontreated cells.
Abstract: We examined the synthesis of early and late simian virus 40 (SV40) mRNA9s in SV40-infected cells treated with two kinds of protein synthesis inhibitors. SV40 stimulated the synthesis of mRNA9s for both large and small tumor antigens in cells pretreated with the drug emetine before the addition of virus. Emetine is a stringent inhibitor of protein synthesis and, thus, protein factors necessary for transcription and processing of these mRNA9s probably preexist in the cell. Surprisingly, infection of cells pretreated with the protein synthesis inhibitor cycloheximide stimulated the synthesis of about 10-fold-higher levels of early viral mRNA9s than did comparable infections of nontreated cells. This amplification of early viral mRNA steady-state levels is probably not due to inhibition of synthesis of the early A gene product since the same degree of drug-specific amplification was seen in SV40 tsA -infected cells that were cultured at the nonpermissive temperature. However, the most interesting effect of cycloheximide addition on viral mRNA synthesis was its stimulation of the appearance of late mRNA9s in the cytoplasm of cells at early periods of infection. The synthesis of late mRNA9s does not appear to require the A gene product as late RNAs can be found in the cytoplasm of cells infected with SV40 tsA mutants which have been maintained at 41°C and continuously cultured in the presence of cycloheximide. Images

24 citations

Journal ArticleDOI
TL;DR: All the plant products, except for baobab, significantly inhibited iron uptake from FeSO4 and FAC, with fenugreek sprout being the most inhibitory.

23 citations

Journal ArticleDOI
TL;DR: Data show that disruption of aleurone cell walls could increase iron bioaccessibility, and Micromilled aleur one could provide an alternative strategy for iron fortification of cereal products.
Abstract: Cereals constitute important sources of iron in human diet; however, much of the iron in wheat is lost during processing for the production of white flour. This study employed novel food processing techniques to increase the bioaccessibility of naturally occurring iron in wheat. Iron was localized in wheat by Perl’s Prussian blue staining. Soluble iron from digested wheat flour was measured by a ferrozine spectrophotometric assay. Iron bioaccessibility was determined using an in vitro simulated peptic–pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Light microscopy revealed that iron in wheat was encapsulated in cells of the aleurone layer and remained intact after in vivo digestion and passage through the gastrointestinal tract. The solubility of iron in wholegrain wheat and in purified wheat aleurone increased significantly after enzymatic digestion with Driselase, and following mechanical disruption using micromilling. Furthermore, fol...

23 citations

Journal ArticleDOI
TL;DR: It is shown that the CRE factor is an heterodimer between a 43 kDa and the ‘73 kDa’ CRE‐binding proteins and the latter is identified as ATF‐2 (also named CRE‐BPI), a protein implicated in recruiting transcriptional activators to promoters, able to form heterodimers with Jun and for which a sequence‐deduced MW of 55 kDa had been previously reported.

23 citations


Cited by
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Journal ArticleDOI
23 Jan 2004-Cell
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.

32,946 citations

Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

22,269 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
23 Jan 2009-Cell
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.

18,036 citations

Journal ArticleDOI
TL;DR: In this paper, a procedure for extracting plasmid DNA from bacterial cells is described, which is simple enough to permit the analysis by gel electrophoresis of 100 or more clones per day, yet yields DNA which is pure enough to be digestible by restriction enzymes.
Abstract: A procedure for extracting plasmid DNA from bacterial cells is described. The method is simple enough to permit the analysis by gel electrophoresis of 100 or more clones per day yet yields plasmid DNA which is pure enough to be digestible by restriction enzymes. The principle of the method is selective alkaline denaturation of high molecular weight chromosomal DNA while covalently closed circular DNA remains double-stranded. Adequate pH control is accomplished without using a pH meter. Upon neutralization, chromosomal DNA renatures to form an insoluble clot, leaving plasmid DNA in the supernatant. Large and small plasmid DNAs have been extracted by this method.

13,805 citations