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71.
Graupera M Guillermet-Guibert J Foukas LC Phng LK Cain RJ Salpekar A Pearce W Meek S Millan J Cutillas PR Smith AJ Ridley AJ Ruhrberg C Gerhardt H Vanhaesebroeck B 《Nature》2008,453(7195):662-666
Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis. 相似文献
72.
为了研究纳滤去除某市河水中微污染物生产饮用水的可行性,并筛选生产饮用水的最佳纳滤膜,采用四种纳滤膜DESAL 51 HL、DESAL 5 DL、UTC-20和UTC-60处理河水,研究其去除COD、UV254吸收值以及硝酸盐等微污染物效率,考察纳滤过程中水通量变化.试验结果表明,四种膜对COD和具254nm吸收值的有机物去除率在50%~95%之间,UTC-20去除有机物效率最高.DESAL 51 HL、DESAL 5 DL和UTC 60对无机物截留率在22%~65%之间,而UTC-20达到93%.UTC-20对不同原水中硝酸盐的去除率均大于70%.在短时间纳滤实验中,存在着不可逆的水通量减少,有轻度膜污染发生.结论UTC-20适用于处理有机污染和硝酸盐复合污染的地表水源生产饮用水. 相似文献
73.
Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome 总被引:1,自引:0,他引:1
Koolen DA Kramer JM Neveling K Nillesen WM Moore-Barton HL Elmslie FV Toutain A Amiel J Malan V Tsai AC Cheung SW Gilissen C Verwiel ET Martens S Feuth T Bongers EM de Vries P Scheffer H Vissers LE de Brouwer AP Brunner HG Veltman JA Schenck A Yntema HG de Vries BB 《Nature genetics》2012,44(6):639-641
We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes. 相似文献
74.
A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels 总被引:1,自引:1,他引:0
75.
Paleoproteomic study of the Iceman’s brain tissue 总被引:1,自引:1,他引:0
Frank Maixner Thorsten Overath Dennis Linke Marek Janko Gea Guerriero Bart H. J. van den Berg Bjoern Stade Petra Leidinger Christina Backes Marta Jaremek Benny Kneissl Benjamin Meder Andre Franke Eduard Egarter-Vigl Eckart Meese Andreas Schwarz Andreas Tholey Albert Zink Andreas Keller 《Cellular and molecular life sciences : CMLS》2013,70(19):3709-3722
The Tyrolean Iceman, a Copper-age ice mummy, is one of the best-studied human individuals. While the genome of the Iceman has largely been decoded, tissue-specific proteomes have not yet been investigated. We studied the proteome of two distinct brain samples using gel-based and liquid chromatography–mass spectrometry-based proteomics technologies together with a multiple-databases and -search algorithms-driven data-analysis approach. Thereby, we identified a total of 502 different proteins. Of these, 41 proteins are known to be highly abundant in brain tissue and 9 are even specifically expressed in the brain. Furthermore, we found 10 proteins related to blood and coagulation. An enrichment analysis revealed a significant accumulation of proteins related to stress response and wound healing. Together with atomic force microscope scans, indicating clustered blood cells, our data reopens former discussions about a possible injury of the Iceman’s head near the site where the tissue samples have been extracted. 相似文献
76.
77.
Young ND Debellé F Oldroyd GE Geurts R Cannon SB Udvardi MK Benedito VA Mayer KF Gouzy J Schoof H Van de Peer Y Proost S Cook DR Meyers BC Spannagl M Cheung F De Mita S Krishnakumar V Gundlach H Zhou S Mudge J Bharti AK Murray JD Naoumkina MA Rosen B Silverstein KA Tang H Rombauts S Zhao PX Zhou P Barbe V Bardou P Bechner M Bellec A Berger A Bergès H Bidwell S Bisseling T Choisne N Couloux A Denny R Deshpande S Dai X Doyle JJ Dudez AM Farmer AD Fouteau S Franken C Gibelin C Gish J Goldstein S 《Nature》2011,480(7378):520-524
Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ~94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox. 相似文献
78.
Parvari R Hershkovitz E Grossman N Gorodischer R Loeys B Zecic A Mortier G Gregory S Sharony R Kambouris M Sakati N Meyer BF Al Aqeel AI Al Humaidan AK Al Zanhrani F Al Swaid A Al Othman J Diaz GA Weiner R Khan KT Gordon R Gelb BD;HRD/Autosomal Recessive Kenny-Caffey Syndrome Consortium 《Nature genetics》2002,32(3):448-452
The syndrome of congenital hypoparathyroidism, mental retardation, facial dysmorphism and extreme growth failure (HRD or Sanjad-Sakati syndrome; OMIM 241410) is an autosomal recessive disorder reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections has been classified as autosomal recessive Kenny-Caffey syndrome (AR-KCS; OMIM 244460). Both traits have previously been mapped to chromosome 1q43-44 (refs 5,6) and, despite the observed clinical variability, share an ancestral haplotype, suggesting a common founder mutation. We describe refinement of the critical region to an interval of roughly 230 kb and identification of deletion and truncation mutations of TBCE in affected individuals. The gene TBCE encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers. Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. These findings demonstrate that HRD and AR-KCS are chaperone diseases caused by a genetic defect in the tubulin assembly pathway, and establish a potential connection between tubulin physiology and the development of the parathyroid. 相似文献
79.
80.