排序方式: 共有38条查询结果,搜索用时 15 毫秒
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Kristin T. Jacobsen Kerstin Iverfeldt 《Cellular and molecular life sciences : CMLS》2009,66(14):2299-2318
The Alzheimer’s amyloid precursor protein (APP) belongs to a conserved gene family that also includes the mammalian APLP1
and APLP2, the Drosophila APPL, and the C. elegans APL-1. The biological function of APP is still not fully clear. However, it is known that the APP family proteins have redundant
and partly overlapping functions, which demonstrates the importance of studying all APP family members to gain a more complete
picture. When APP was first cloned, it was speculated that it could function as a receptor. This theory has been further substantiated
by studies showing that APP and its homologues bind both extracellular ligands and intracellular adaptor proteins. The APP
family proteins undergo regulated intramembrane proteolysis (RIP), generating secreted and cytoplasmic fragments that have
been ascribed different functions. In this review, we will discuss the APP family with focus on biological functions, binding
partners, and regulated processing. 相似文献
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Metabolic priming by a secreted fungal effector 总被引:1,自引:0,他引:1
Djamei A Schipper K Rabe F Ghosh A Vincon V Kahnt J Osorio S Tohge T Fernie AR Feussner I Feussner K Meinicke P Stierhof YD Schwarz H Macek B Mann M Kahmann R 《Nature》2011,478(7369):395-398
Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation. 相似文献
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Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants 总被引:2,自引:0,他引:2
Wellcome Trust Case Control Consortium;Australo-Anglo-American Spondylitis Consortium 《Nature genetics》2007,39(11):1329-1337
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases. 相似文献
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A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse 总被引:1,自引:0,他引:1
Rosengren Pielberg G Golovko A Sundström E Curik I Lennartsson J Seltenhammer MH Druml T Binns M Fitzsimmons C Lindgren G Sandberg K Baumung R Vetterlein M Strömberg S Grabherr M Wade C Lindblad-Toh K Pontén F Heldin CH Sölkner J Andersson L 《Nature genetics》2008,40(8):1004-1009
In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals. 相似文献
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The twentieth century was the wettest period in northern Pakistan over the past millennium 总被引:1,自引:0,他引:1
Twentieth-century warming could lead to increases in the moisture-holding capacity of the atmosphere, altering the hydrological cycle and the characteristics of precipitation. Such changes in the global rate and distribution of precipitation may have a greater direct effect on human well-being and ecosystem dynamics than changes in temperature itself. Despite the co-variability of both of these climate variables, attention in long-term climate reconstruction has mainly concentrated on temperature changes. Here we present an annually resolved oxygen isotope record from tree-rings, providing a millennial-scale reconstruction of precipitation variability in the high mountains of northern Pakistan. The climatic signal originates mainly from winter precipitation, and is robust over ecologically different sites. Centennial-scale variations reveal dry conditions at the beginning of the past millennium and through the eighteenth and early nineteenth centuries, with precipitation increasing during the late nineteenth and the twentieth centuries to yield the wettest conditions of the past 1,000 years. Comparison with other long-term precipitation reconstructions indicates a large-scale intensification of the hydrological cycle coincident with the onset of industrialization and global warming, and the unprecedented amplitude argues for a human role. 相似文献
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Karlsson EK Baranowska I Wade CM Salmon Hillbertz NH Zody MC Anderson N Biagi TM Patterson N Pielberg GR Kulbokas EJ Comstock KE Keller ET Mesirov JP von Euler H Kämpe O Hedhammar A Lander ES Andersson G Andersson L Lindblad-Toh K 《Nature genetics》2007,39(11):1321-1328
With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with approximately 27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only approximately 20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of approximately 100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health. 相似文献
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Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
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Larsson P Oyston PC Chain P Chu MC Duffield M Fuxelius HH Garcia E Hälltorp G Johansson D Isherwood KE Karp PD Larsson E Liu Y Michell S Prior J Prior R Malfatti S Sjöstedt A Svensson K Thompson N Vergez L Wagg JK Wren BW Lindler LE Andersson SG Forsman M Titball RW 《Nature genetics》2005,37(2):153-159
Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them. 相似文献