排序方式: 共有27条查询结果,搜索用时 15 毫秒
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Goudie DR D'Alessandro M Merriman B Lee H Szeverényi I Avery S O'Connor BD Nelson SF Coats SE Stewart A Christie L Pichert G Friedel J Hayes I Burrows N Whittaker S Gerdes AM Broesby-Olsen S Ferguson-Smith MA Verma C Lunny DP Reversade B Lane EB 《Nature genetics》2011,43(4):365-369
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer. 相似文献
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Geneviève D Proulle V Isidor B Bellais S Serre V Djouadi F Picard C Vignon-Savoye C Bader-Meunier B Blanche S de Vernejoul MC Legeai-Mallet L Fischer AM Le Merrer M Dreyfus M Gaussem P Munnich A Cormier-Daire V 《Nature genetics》2008,40(3):284-286
Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts. 相似文献
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Stevanin G Santorelli FM Azzedine H Coutinho P Chomilier J Denora PS Martin E Ouvrard-Hernandez AM Tessa A Bouslam N Lossos A Charles P Loureiro JL Elleuch N Confavreux C Cruz VT Ruberg M Leguern E Grid D Tazir M Fontaine B Filla A Bertini E Durr A Brice A 《Nature genetics》2007,39(3):366-372
Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP. 相似文献
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Anne-Marie Bourdeaux Y. Giudicelli Marie-Christine Rebourcet J. Nordmann R. Nordmann 《Cellular and molecular life sciences : CMLS》1980,36(8):913-914
Summary Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue.Acknowledgments. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Université René Descartes (Paris V) and the École Pratique des Hautes-Etudes (3e Section). 相似文献
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Apoptotic cell-derived factors induce arginase II expression in murine macrophages by activating ERK5/CREB 总被引:1,自引:1,他引:0
Barra V Kuhn AM von Knethen A Weigert A Brüne B 《Cellular and molecular life sciences : CMLS》2011,68(10):1815-1827
Apoptotic cell (AC)-derived factors alter the physiology of macrophages (MΦs) towards a regulatory phenotype, characterized
by reduced nitric oxide (NO) production. Impaired NO formation in response to AC-conditioned medium (CM) was facilitated by
arginase II (ARG II) expression, which competes with inducible NO synthase for l-arginine. Here we explored signaling pathways allowing CM to upregulate ARG II in RAW264.7 MΦs. Sphingosine-1-phosphate (S1P)
was required and acted synergistically with a so far unidentified factor to elicit high ARG II expression. S1P activated S1P2, since S1P2 knockdown prevented ARG II upregulation. Furthermore, ERK5 knockdown attenuated CM-mediated ARG II protein induction. CREB
was implicated as shown by EMSA analysis and decoy-oligonucleotides scavenging CREB in RAW264.7 MΦs, which blocked ARG II
expression. We conclude that AC-derived S1P binds to S1P2 and acts synergistically with other factors to activate ERK5 and concomitantly CREB. This signaling cascade shapes an anti-inflammatory
MΦ phenotype by ARG II induction. 相似文献