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排序方式: 共有65条查询结果,搜索用时 15 毫秒
31.
Esau C Davis S Murray SF Yu XX Pandey SK Pear M Watts L Booten SL Graham M McKay R Subramaniam A Propp S Lollo BA Freier S Bennett CF Bhanot S Monia BP 《Cell metabolism》2006,3(2):87-98
Current understanding of microRNA (miRNA) biology is limited, and antisense oligonucleotide (ASO) inhibition of miRNAs is a powerful technique for their functionalization. To uncover the role of the liver-specific miR-122 in the adult liver, we inhibited it in mice with a 2'-O-methoxyethyl phosphorothioate ASO. miR-122 inhibition in normal mice resulted in reduced plasma cholesterol levels, increased hepatic fatty-acid oxidation, and a decrease in hepatic fatty-acid and cholesterol synthesis rates. Activation of the central metabolic sensor AMPK was also increased. miR-122 inhibition in a diet-induced obesity mouse model resulted in decreased plasma cholesterol levels and a significant improvement in liver steatosis, accompanied by reductions in several lipogenic genes. These results implicate miR-122 as a key regulator of cholesterol and fatty-acid metabolism in the adult liver and suggest that miR-122 may be an attractive therapeutic target for metabolic disease. 相似文献
32.
Pei-Hsun Cheng Brooke Snyder Dimitri Fillos Chris C Ibegbu Anderson Hsien-Cheng Huang Anthony WS Chan 《BMC cell biology》2008,9(1):20
Background
Chimpanzee dental pulp stem/stromal cells (ChDPSCs) are very similar to human bone marrow derived mesenchymal stem/stromal cells (hBMSCs) as demonstrated by the expression pattern of cell surface markers and their multipotent differentiation capability. 相似文献33.
The diverse roles that Notch signals play during the development and maintenance of normal tissues are recapitulated in different forms of cancer. Depending on the tumor type, Notch can variously promote or limit tumor growth through either cell autonomous or cell non-autonomous effects on differentiation, cellular metabolism, cell cycle progression, angiogenesis, and possibly self-renewal and immune function. Of particular interest, recent findings indicate that a high fraction of T-cell acute lymphoblastic leukemias and lymphomas have activating mutations in the Notch 1 receptor, and that Notch signaling might have a role in the maintenance of normal and malignant stem cells. 相似文献
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35.
Aster JC Bodnar N Xu L Karnell F Milholland JM Maillard I Histen G Nam Y Blacklow SC Pear WS 《PloS one》2011,6(10):e25645
Background
The functional interchangeability of mammalian Notch receptors (Notch1-4) in normal and pathophysiologic contexts such as cancer is unsettled. We used complementary in vivo, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and maintain T-ALL cell growth and survival.Principal Findings
We find that the activated intracellular domains of Notch1-4 (ICN1-4) all support T cell development in mice and thymic organ culture. However, unlike ICN1-3, ICN4 fails to induce T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and is unable to rescue the growth of Notch1-dependent T-ALL cell lines. The ICN4 phenotype is mimicked by weak gain-of-function forms of Notch1, suggesting that it stems from a failure to transactivate one or more critical target genes above a necessary threshold. Experiments with chimeric receptors demonstrate that the Notch ankyrin repeat domains differ in their leukemogenic potential, and that this difference correlates with activation of Myc, a direct Notch target that has an important role in Notch-associated T-ALL.Conclusions/Significance
We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis. 相似文献36.
Background
SXT is an integrating conjugative element (ICE) originally isolated from Vibrio cholerae, the bacterial pathogen that causes cholera. It houses multiple antibiotic and heavy metal resistance genes on its ca. 100 kb circular double stranded DNA (dsDNA) genome, and functions as an effective vehicle for the horizontal transfer of resistance genes within susceptible bacterial populations. Here, we characterize the activities of an alkaline exonuclease (S066, SXT-Exo) and single strand annealing protein (S065, SXT-Bet) encoded on the SXT genetic element, which share significant sequence homology with Exo and Bet from bacteriophage lambda, respectively.Results
SXT-Exo has the ability to degrade both linear dsDNA and single stranded DNA (ssDNA) molecules, but has no detectable endonuclease or nicking activities. Adopting a stable trimeric arrangement in solution, the exonuclease activities of SXT-Exo are optimal at pH 8.2 and essentially require Mn2+ or Mg2+ ions. Similar to lambda-Exo, SXT-Exo hydrolyzes dsDNA with 5'- to 3'-polarity in a highly processive manner, and digests DNA substrates with 5'-phosphorylated termini significantly more effectively than those lacking 5'-phosphate groups. Notably, the dsDNA exonuclease activities of both SXT-Exo and lambda-Exo are stimulated by the addition of lambda-Bet, SXT-Bet or a single strand DNA binding protein encoded on the SXT genetic element (S064, SXT-Ssb). When co-expressed in E. coli cells, SXT-Bet and SXT-Exo mediate homologous recombination between a PCR-generated dsDNA fragment and the chromosome, analogous to RecET and lambda-Bet/Exo.Conclusions
The activities of the SXT-Exo protein are consistent with it having the ability to resect the ends of linearized dsDNA molecules, forming partially ssDNA substrates for the partnering SXT-Bet single strand annealing protein. As such, SXT-Exo and SXT-Bet may function together to repair or process SXT genetic elements within infected V. cholerae cells, through facilitating homologous DNA recombination events. The results presented here significantly extend our general understanding of the properties and activities of alkaline exonuclease and single strand annealing proteins of viral/bacteriophage origin, and will assist the rational development of bacterial recombineering systems. 相似文献37.
Komine O Nagaoka M Hiraoka Y Hoshino M Kawaguchi Y Pear WS Tanaka K 《Developmental biology》2011,(1):44-54
During brain development, neurons and glias are generated from neural stem cells and more limited intermediate neural progenitors (INPs). Numerous studies have revealed the mechanisms of development of neural stem cells. However, the signaling pathways that govern the development of INPs are largely unknown. The cerebellum is suitable for examining this issue because cerebellar cortical inhibitory neurons such as basket and stellate cells are derived from small Pax2+ interneuronal progenitors. Here, we show that Sox2−/Pax2+ and Sox2+/Pax2− progenitors, 2 types of interneuronal progenitors of basket and stellate cells, exist in the cerebellar white matter (WM) and that the former arise from the latter during the first postnatal week. Moreover, RBP-J promotes the neurogenesis of stellate and basket cells by converting Sox2+/Pax2− interneuronal progenitors to more mature Sox2−/Pax2+ interneuronal progenitors. This study shows a novel RBP-J function that promotes INP differentiation. 相似文献
38.
39.
Mercher T Cornejo MG Sears C Kindler T Moore SA Maillard I Pear WS Aster JC Gilliland DG 《Cell Stem Cell》2008,3(3):314-326
In the hematopoietic system, Notch signaling specifies T cell lineage fate, in part through negative regulation of B cell and myeloid lineage development. However, we unexpectedly observed the development of megakaryocytes when using heterotypic cocultures of hematopoietic stem cells with OP9 cells expressing Delta-like1, but not with parental OP9 cells. This effect was abrogated by inhibition of Notch signaling either with gamma-secretase inhibitors or by expression of the dominant-negative Mastermind-like1. The importance of Notch signaling for megakaryopoietic development in vivo was confirmed by using mutant alleles that either activate or inhibit Notch signaling. These findings indicate that Notch is a positive regulator of megakaryopoiesis and plays a more complex role in cell-fate decisions among myeloid progenitors than previously appreciated. 相似文献
40.
WS Watkins R Thara BJ Mowry Y Zhang DJ Witherspoon W Tolpinrud MJ Bamshad S Tirupati R Padmavati H Smith D Nancarrow C Filippich LB Jorde 《BMC genetics》2008,9(1):1-17