排序方式: 共有6条查询结果,搜索用时 15 毫秒
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Carninci P Sandelin A Lenhard B Katayama S Shimokawa K Ponjavic J Semple CA Taylor MS Engström PG Frith MC Forrest AR Alkema WB Tan SL Plessy C Kodzius R Ravasi T Kasukawa T Fukuda S Kanamori-Katayama M Kitazume Y Kawaji H Kai C Nakamura M Konno H Nakano K Mottagui-Tabar S Arner P Chesi A Gustincich S Persichetti F Suzuki H Grimmond SM Wells CA Orlando V Wahlestedt C Liu ET Harbers M Kawai J Bajic VB Hume DA Hayashizaki Y 《Nature genetics》2006,38(6):626-635
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Schmid D Stolzlechner M Sorgner A Bentele C Assinger A Chiba P Moeslinger T 《Cellular and molecular life sciences : CMLS》2012,69(1):129-148
An alternatively spliced form of human sulfonylurea receptor (SUR) 1 mRNA lacking exon 2 (SUR1Δ2) has been identified. The
omission of exon 2 caused a frame shift and an immediate stop codon in exon 3 leading to translation of a 5.6-kDa peptide
that comprises the N-terminal extracellular domain and the first transmembrane helix of SUR1. Based on a weak first splice
acceptor site in the human SUR1 gene (ABCC8), RT-PCR revealed a concurrent expression of SUR1Δ2 and SUR1. The SUR1Δ2/(SUR1 + SUR1Δ2)
mRNA ratio differed between tissues, and was lowest in pancreas (46%), highest in heart (88%) and negatively correlated with
alternative splice factor/splicing factor 2 (ASF/SF2) expression. In COS-7 cells triple transfected with SUR1Δ2/SUR1/Kir6.2,
the SUR1Δ2 peptide co-immunoprecipitated with Kir6.2, thereby displacing two of four SUR1 subunits on the cell surface. The
ATP sensitivity of these hybrid ATP-sensitive potassium channels (KATP) channels was reduced by about sixfold, as shown with single-channel recordings. RINm5f rat insulinoma cells, which genuinely
express SUR1 but not SUR1Δ2, exhibited a strongly increased KATP channel current upon transfection with SUR1Δ2. This led to inhibition of glucose-induced depolarization, calcium flux, insulin
release and glibenclamide action. A non-mutagenic SNP on nucleotide position 333 (Pro69Pro) added another exonic splicing
enhancer sequence detected by ASF/SF2, reduced relative abundance of SUR1Δ2 and slightly protected from non-insulin dependent
diabetes in homozygotic individuals. Thus, SUR1Δ2 represents an endogenous KATP-channel modulator with prodiabetic properties in islet cells. Its predominance in heart may explain why high-affinity sulfonylurea
receptors are not found in human cardiac tissue. 相似文献
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Corinne Abbadie Olivier Pluquet Albin Pourtier 《Cellular and molecular life sciences : CMLS》2017,74(24):4471-4509
Senescence is a cell state occurring in vitro and in vivo after successive replication cycles and/or upon exposition to various stressors. It is characterized by a strong cell cycle arrest associated with several molecular, metabolic and morphologic changes. The accumulation of senescent cells in tissues and organs with time plays a role in organismal aging and in several age-associated disorders and pathologies. Moreover, several therapeutic interventions are able to prematurely induce senescence. It is, therefore, tremendously important to characterize in-depth, the mechanisms by which senescence is induced, as well as the precise properties of senescent cells. For historical reasons, senescence is often studied with fibroblast models. Other cell types, however, much more relevant regarding the structure and function of vital organs and/or regarding pathologies, are regrettably often neglected. In this article, we will clarify what is known on senescence of epithelial cells and highlight what distinguishes it from, and what makes it like, replicative senescence of fibroblasts taken as a standard. 相似文献
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This paper compares Feyerabend's arguments in Science in a Free Society to the controversial theory of expertise proposed by Harry Collins and Robert Evans as a Third Wave of Science Studies. Is the legitimacy of democratic decisions threatened by the unquestioned authority of scientific advice? Or does, on the contrary, science need protection from too much democratic participation in technical decisions? Where Feyerabend's political relativism envisions democratic society as inherently pluralist and demands equal contribution of all traditions and worldviews to public decision-making, Collins and Evans hold a conception of elective modernism, defending the reality and value of technical expertise and arguing that science deserves a privileged status in modern democracies, because scientific values are also democratic values. I will argue that Feyerabend's political relativism provides a valuable framework for the evaluation of Collins' and Evans' theory of expertise. By constructing a dialog between Feyerabend and this more recent approach in Science and Technology Studies, the aim of this article is not only to show where the two positions differ and in what way they might be reconciled, but also how Feyerabend's philosophy provides substantial input to contemporary debate. 相似文献
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Bomar JM Benke PJ Slattery EL Puttagunta R Taylor LP Seong E Nystuen A Chen W Albin RL Patel PD Kittles RA Sheffield VC Burmeister M 《Nature genetics》2003,35(3):264-269
Cayman ataxia is a recessive congenital ataxia restricted to one area of Grand Cayman Island. Comparative mapping suggested that the locus on 19p13.3 associated with Cayman ataxia might be homologous to the locus on mouse chromosome 10 associated with the recessive ataxic mouse mutant jittery. Screening genes in the region of overlap identified mutations in a novel predicted gene in three mouse jittery alleles, including the first mouse mutation caused by an Alu-related (B1 element) insertion. We found two mutations exclusively in all individuals with Cayman ataxia. The gene ATCAY or Atcay encodes a neuron-restricted protein called caytaxin. Caytaxin contains a CRAL-TRIO motif common to proteins that bind small lipophilic molecules. Mutations in another protein containing a CRAL-TRIO domain, alpha-tocopherol transfer protein (TTPA), cause a vitamin E-responsive ataxia. Three-dimensional protein structural modeling predicts that the caytaxin ligand is more polar than vitamin E. Identification of the caytaxin ligand may help develop a therapy for Cayman ataxia. 相似文献
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