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991.
Scott RH Douglas J Baskcomb L Huxter N Barker K Hanks S Craft A Gerrard M Kohler JA Levitt GA Picton S Pizer B Ronghe MD Williams D;Factors Associated with Childhood Tumours 《Nature genetics》2008,40(11):1329-1334
Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor. 相似文献
992.
Arachiche A Badirou I Dachary-Prigent J Garcin I Geldwerth-Feniger D Kerbiriou-Nabias D 《Cellular and molecular life sciences : CMLS》2008,65(23):3861-3871
Rapid Ca2+-dependent phospholipid (PL) reorganization (scrambling) at the plasma membrane is a mechanism common to hematopoietic cells
exposing procoagulant phosphatidylserine (PS). The aim of this research was to determine whether activation of the extracellular
signal-regulated kinase (ERK) pathway was required for PL scrambling, based on a single report analyzing both responses induced
by Ca2+ ionophores in megakaryoblastic HEL cells. Ca2+ ionophore-stimulated ERK phosphorylation was induced in platelets without external Ca2+, whereas exogenous Ca2+ entry was crucial for ERK activation in Jurkat T cells. In both cells, membrane scrambling only occurred following Ca2+ entry and was not blocked by inhibiting ERK phosphorylation. Furthermore, ERK proteins are strongly phosphorylated in transformed
B lymphoblastic cell lines, which do not expose PS in their resting state. Overall, the data demonstrated that ERK activation
and membrane scrambling are independent mechanisms.
A. Arachiche, I. Badirou: These authors contributed equally to this work.
Received 18 June 2008; received after revision 24 September 2008; accepted 1 October 2008 相似文献
993.
Taylor DM Maxwell MM Luthi-Carter R Kazantsev AG 《Cellular and molecular life sciences : CMLS》2008,65(24):4000-4018
Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are
key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The
desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven
mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer,
cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets
for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance
to human disease.
Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008 相似文献
994.
Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: Implications for an entatic state 总被引:1,自引:0,他引:1
Bergman T Zhang K Palmberg C Jörnvall H Auld DS 《Cellular and molecular life sciences : CMLS》2008,65(24):4019-4027
Zinc binding to the peptide replica and analogs to residues 93–115 of horse liver alcohol dehydrogenase (ADH) was examined
by competition of the peptides and the chromophoric chelator 4-(2- pyridylazo)resorcinol for zinc and X-ray absorption fine
structure analysis of the zinc ligands. In the enzyme, zinc is coordinated by four Cys residues. In the peptide replica, zinc
is bound to three Cys and one His residue. A four-Cys zinc coordination is observed only when His is removed, leading to increased
zinc stability. ADH crystal structures reveal that the ε-amino group of the conserved residue Lys323 is within H-bond distance
of the backbone amide oxygens of residues 103, 105 and 108, likely stabilizing the zinc coordination in the enzyme. The peptide
data thus indicate structural strain and increased energy in the zinc-binding site in the protein, characteristic of an entatic
state, implying a functional nature for this zinc site.
Received 3 July 2008; received after revision 11 August 2008; accepted 1 September 2008 相似文献
995.
Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively approximately 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease. 相似文献
996.
Twigger SN Pruitt KD Fernández-Suárez XM Karolchik D Worley KC Maglott DR Brown G Weinstock G Gibbs RA Kent J Birney E Jacob HJ 《Nature genetics》2008,40(5):523-527
It has been four years since the original publication of the draft sequence of the rat genome. Five groups are now working together to assemble, annotate and release an updated version of the rat genome. As the prevailing model for physiology, complex disease and pharmacological studies, there is an acute need for the rat's genomic resources to keep pace with the rat's prominence in the laboratory. In this commentary, we describe the current status of the rat genome sequence and the plans for its impending 'upgrade'. We then cover the key online resources providing access to the rat genome, including the new SNP views at Ensembl, the RefSeq and Genes databases at the US National Center for Biotechnology Information, Genome Browser at the University of California Santa Cruz and the disease portals for cardiovascular disease and obesity at the Rat Genome Database. 相似文献
997.
Vitart V Rudan I Hayward C Gray NK Floyd J Palmer CN Knott SA Kolcic I Polasek O Graessler J Wilson JF Marinaki A Riches PL Shu X Janicijevic B Smolej-Narancic N Gorgoni B Morgan J Campbell S Biloglav Z Barac-Lauc L Pericic M Klaric IM Zgaga L Skaric-Juric T Wild SH Richardson WA Hohenstein P Kimber CH Tenesa A Donnelly LA Fairbanks LD Aringer M McKeigue PM Ralston SH Morris AD Rudan P Hastie ND Campbell H Wright AF 《Nature genetics》2008,40(4):437-442
Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes. 相似文献
998.
Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006. 相似文献
999.
1000.
基于Multi-Agent系统的预测支持系统的结构 总被引:1,自引:0,他引:1
Agent技术是人工智能和计算机科学领域内新兴的研究热点,自治Agent和多Agent系统为复杂软件系统的分析、设计和实现提供了新的思路.给出一种基于Multi-Agent系统的预测支持系统的结构,将系统设计成由多个Agent组成的多Agent系统.各个Agent有自己的功能,可以独立自主地运行,还可以协同工作完成系统整体目标. 相似文献