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.

Flavonoid-rich berry-extract treatment decreases glucose uptake in human intestinal Caco-2 cells

Abstract: Berries are a rich dietary source of bioactive polyphenols, including flavonoids, such as anthocyanins. Dietary flavonoids are known to decrease the expression of the facilitative GLUT2 and the sodium-glucose cotransporter (SGLT1) genes, the two main glucose transporters in human subjects’ intestinal Caco-2 cells. Acute inhibitory effects on glucose absorption have previously been observed in the presence of flavonoids, however, little is known regarding genomic effects on uptake. The present study investigated the influence of a flavonoid-rich berry-extract on glucose uptake in human subject’s intestinal Caco-2 cell monolayers. Human subject’s intestinal Caco-2 cells, cultured for 19 d, were treated, acutely (15 min) or chronically (16 h) with a flavonoid-rich berry-extract (OptiBerry; InterHealth Nutraceuticals, Benicia, CA, USA) at a final concentration of 0.125% (w/v) then subjected to radiolabelled glucose for 2 min, in the presence or absence of Na. Uptake was determined by liquid scintillation counting of cell lysate. Data were normalised to cell protein concentration and presented as uptake as a percentage of control. Statistical significance was determined by Student’s t-test (P £ 0.05; n 12). Results indicated that berry flavonoids significantly decrease glucose uptake in human subject’s intestinal Caco-2 cells both acutely and chronically. These inhibitory effects are evident in both Na -dependent and Na -independent glucose uptake pathways. Studies are in progress to investigate the biological relevance of the observed effects in relation to berry consumption and glucose metabolism. Potentially, such berry-extracts may be useful in the dietary modulation of postprandial glucose homeostasis.

19 The Biology of Short RNAs

Abstract: The RNA World is commonly discussed in the context of RNA catalysis. During this ancient stage of biology, however—where the genetic material consisted of RNA and many processes were catalyzed by RNA—RNA was almost certainly also the major regulatory molecule controlling both the flow of information and the rate of catalytic processes. Elsewhere in this volume, RNA is described as regulating many common processes such as translation, RNA splicing, and protein functions. These regulatory interactions use a combination of RNA features—primary sequence, secondary and tertiary structure—for recognition of other components for regulation. Given the complexity of known RNA molecules involved in regulation, it was a major surprise when simple RNAs of only about 22 nucleotides in length were found to have many general functions in the regulation of biological systems. These short RNAs are derived from double-stranded RNA (dsRNA) precursors, are recognized by multicomponent machinery in cells, and direct the regulation of gene expression through their primary sequence. The discovery of these RNA interference (RNAi)-related processes have radically changed concepts about the nature of regulatory factors in organisms. In theory, any linear sequence of RNA can be converted into a trans -acting regulatory factor by small RNA regulatory mechanisms. Small RNAs are now known to regulate expression of information in DNA sequences at the level of mRNA stability, mRNA translation, and transcription of RNA. Although it is possible that these processes utilizing short RNAs had their origins in the RNA World, it seems more likely that these...

Initial sequencing and analysis of the human genome.

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.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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。

A rapid alkaline extraction procedure for screening recombinant plasmid DNA

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.