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排序方式: 共有195条查询结果,搜索用时 234 毫秒
161.
Albers CA Paul DS Schulze H Freson K Stephens JC Smethurst PA Jolley JD Cvejic A Kostadima M Bertone P Breuning MH Debili N Deloukas P Favier R Fiedler J Hobbs CM Huang N Hurles ME Kiddle G Krapels I Nurden P Ruivenkamp CA Sambrook JG Smith K Stemple DL Strauss G Thys C van Geet C Newbury-Ecob R Ouwehand WH Ghevaert C 《Nature genetics》2012,44(4):435-9, S1-2
162.
Frédéric?Delolme Cyril?Anastasi Lindsay?B.?Alcaraz Valentin?Mendoza Sandrine?Vadon-Le Goff Maya?Talantikite Robin?Capomaccio Jimmy?Mevaere La?titia?Fortin Dominique?Mazzocut Odile?Damour Isabelle?Zanella-Cléon David?J.?S.?Hulmes Christopher?M.?Overall Ulrich?Valcourt Fernando?Lopez-Casillas Catherine?MoaliEmail author 《Cellular and molecular life sciences : CMLS》2015,72(5):1009-1027
The metalloproteinase BMP-1 (bone morphogenetic protein-1) plays a major role in the control of extracellular matrix (ECM) assembly and growth factor activation. Most of the growth factors activated by BMP-1 are members of the TGF-β superfamily known to regulate multiple biological processes including embryonic development, wound healing, inflammation and tumor progression. In this study, we used an iTRAQ (isobaric tags for relative and absolute quantification)-based quantitative proteomic approach to reveal the release of proteolytic fragments from the cell surface or the ECM by BMP-1. Thirty-eight extracellular proteins were found in significantly higher or lower amounts in the conditioned medium of HT1080 cells overexpressing BMP-1 and thus, could be considered as candidate substrates. Strikingly, three of these new candidates (betaglycan, CD109 and neuropilin-1) were TGF-β co-receptors, also acting as antagonists when released from the cell surface, and were chosen for further substrate validation. Betaglycan and CD109 proved to be directly cleaved by BMP-1 and the corresponding cleavage sites were extensively characterized using a new mass spectrometry approach. Furthermore, we could show that the ability of betaglycan and CD109 to interact with TGF-β was altered after cleavage by BMP-1, leading to increased and prolonged SMAD2 phosphorylation in BMP-1-overexpressing cells. Betaglycan processing was also observed in primary corneal keratocytes, indicating a general and novel mechanism by which BMP-1 directly affects signaling by controlling TGF-β co-receptor activity. The proteomic data have been submitted to ProteomeXchange with the identifier PXD000786 and doi: 10.6019/PXD000786. 相似文献
163.
Soler Artigas M Loth DW Wain LV Gharib SA Obeidat M Tang W Zhai G Zhao JH Smith AV Huffman JE Albrecht E Jackson CM Evans DM Cadby G Fornage M Manichaikul A Lopez LM Johnson T Aldrich MC Aspelund T Barroso I Campbell H Cassano PA Couper DJ Eiriksdottir G Franceschini N Garcia M Gieger C Gislason GK Grkovic I Hammond CJ Hancock DB Harris TB Ramasamy A Heckbert SR Heliövaara M Homuth G Hysi PG James AL Jankovic S Joubert BR Karrasch S Klopp N Koch B Kritchevsky SB Launer LJ Liu Y Loehr LR 《Nature genetics》2011,43(11):1082-1090
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. 相似文献
164.
Catherine Aude-Garcia Christian Villiers Serge M. Candéias Catherine Garrel Caroline Bertrand Véronique Collin Patrice N. Marche Evelyne Jouvin-Marche 《Cellular and molecular life sciences : CMLS》2011,68(4):687-696
The cellular prion glycoprotein (PrPC) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate
in vitro and in vivo that PrPC is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione,
we show that PrP−/− thymocytes display a higher susceptibility to H2O2 exposure than PrP+/+ cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level
of ROS, PrP−/− thymocytes are more sensitive to oxidative stress. PrPC function appears to be specific for oxidative stress, since no significant differences are observed between PrP−/− and PrP+/+ mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation
in the thymus. Taken together, our results clearly ascribe to PrPC a protective function in thymocytes against oxidative stress. 相似文献
165.
Cooper GM Coe BP Girirajan S Rosenfeld JA Vu TH Baker C Williams C Stalker H Hamid R Hannig V Abdel-Hamid H Bader P McCracken E Niyazov D Leppig K Thiese H Hummel M Alexander N Gorski J Kussmann J Shashi V Johnson K Rehder C Ballif BC Shaffer LG Eichler EE 《Nature genetics》2011,43(9):838-846
To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ~14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders. 相似文献
166.
167.
168.
D. J. Procaccini R. L. Procaccini Catherine M. Doyle 《Cellular and molecular life sciences : CMLS》1971,27(9):1012-1013
Résumé L'oxydase monoamine se trouve sous une forme active dans le foie d'un urodèle adulte capable d'activité normale et régénératrice. Au cours des deux premières heures qui suivent l'amputation d'un membre antérieur, on peut noter une augmentation appréciable de l'activité de l'oxydase monoamine. Cette augmentation indique que la tension physiologique produite par l'amputation rend actifs dans le foie les précurseurs de l'oxydase monoamine qui peuvent, à leur tour, stimuler un métabolisme plus rapide et augmenter la quantité des catécholamines qui circulent. 相似文献
169.
170.
M. Hollingsworth Catherine N. M. Isherwood 《Cellular and molecular life sciences : CMLS》1979,35(1):72-73
Summary Field stimulation of isolated, spirally-cut cervix from day-22 pregnant rats produced contractions which could be inhibited by tetrodotoxin or hyoscine and potentiated by propranolol. The rat cervix would appear to receive both cholinergic and noradrenergic innervations whose transmitters activate muscarinic cholinoceptors and -adrenoceptors respectively.We thank the Lalor Foundation, USA, for financial support. 相似文献