SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:0028 0836 OR L773:1476 4687 "

Sökning: L773:0028 0836 OR L773:1476 4687

Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
981.
  • Pinto, Dalila, et al. (författare)
  • Functional impact of global rare copy number variation in autism spectrum disorders.
  • 2010
  • Ingår i: Nature. - 0028-0836. ; 466:7304, s. 368-372
  • Tidskriftsartikel (refereegranskat)abstract
    • The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
  •  
982.
  •  
983.
  • Pizzari, Tommaso, et al. (författare)
  • Sophisticated sperm allocation in male fowl
  • 2003
  • Ingår i: Nature. - 0028-0836. ; 426:6962, s. 70-74
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>When a female is sexually promiscuous, the ejaculates of different males compete for the fertilization of her eggs; the more sperm a male inseminates into a female, the more likely he is to fertilize her eggs. Because sperm production is limited and costly, theory predicts that males will strategically allocate sperm (1) according to female promiscuity, (2) saving some for copulations with new females, and (3) to females producing more and/or better offspring. Whether males allocate sperm in all of these ways is not known, particularly in birds where the collection of natural ejaculates only recently became possible. Here we demonstrate male sperm allocation of unprecedented sophistication in the fowl Gallus gallus. Males show status-dependent sperm investment in females according to the level of female promiscuity; they progressively reduce sperm investment in a particular female but, on encountering a new female, instantaneously increase their sperm investment; and they preferentially allocate sperm to females with large sexual ornaments signalling superior maternal investment. Our results indicate that female promiscuity leads to the evolution of sophisticated male sexual behaviour.</p>
  •  
984.
  •  
985.
  • Poy, MN, et al. (författare)
  • A pancreatic islet-specific microRNA regulates insulin secretion
  • 2004
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836. ; 432:7014, s. 226-230
  • Tidskriftsartikel (refereegranskat)abstract
    • MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si) RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes.
  •  
986.
  • Price, T. D., et al. (författare)
  • Niche filling slows the diversification of Himalayan songbirds
  • 2014
  • Ingår i: Nature. - 0028-0836. ; 509:7499, s. 222-+
  • Tidskriftsartikel (refereegranskat)abstract
    • Speciation generally involves a three-step process-range expansion, range fragmentation and the development of reproductive isolation between spatially separated populations(1,2). Speciation relies on cycling through these three steps and each may limit the rate at which new species form(1,3). We estimate phylogenetic relationships among all Himalayan songbirds to ask whether the development of reproductive isolation and ecological competition, both factors that limit range expansions(4), set an ultimate limit on speciation. Based on a phylogeny for all 358 species distributed along the eastern elevational gradient, here we show that body size and shape differences evolved early in the radiation, with the elevational band occupied by a species evolving later. These results are consistent with competition for niche space limiting species accumulation(5). Even the elevation dimension seems to be approaching ecological saturation, because the closest relatives both inside the assemblage and elsewhere in the Himalayas are on average separated by more than five million years, which is longer than it generally takes for reproductive isolation to be completed(2,3,6); also, elevational distributions are well explained by resource availability, notably the abundance of arthropods, and not by differences in diversification rates in different elevational zones. Our results imply that speciation rate is ultimately set by niche filling(that is, ecological competition for resources), rather than by the rate of acquisition of reproductive isolation.
  •  
987.
  •  
988.
  •  
989.
  •  
990.
  • Raffel, Simon, et al. (författare)
  • BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation
  • 2017
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836. ; 551:7680, s. 384-388
  • Tidskriftsartikel (refereegranskat)abstract
    • The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Further to its role in the tricarboxylic acid cycle, αKG is an essential cofactor for αKG-dependent dioxygenases such as Egl-9 family hypoxia inducible factor 1 (EGLN1) and the ten-eleven translocation (TET) family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG, leading to EGLN1-mediated HIF1α protein degradation. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. By contrast, overexpression of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation through altered TET activity. AML with high levels of BCAT1 (BCAT1high) displayed a DNA hypermethylation phenotype similar to cases carrying a mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHWTTET2WT, but not IDHmut or TET2mut AML. Gene sets characteristic for IDHmut AML were enriched in samples from patients with an IDHWTTET2WTBCAT1high status. BCAT1high AML showed robust enrichment for leukaemia stem-cell signatures, and paired sample analysis showed a significant increase in BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1α stability and regulation of the epigenomic landscape, mimicking the effects of IDH mutations. Our results suggest the BCAA-BCAT1-αKG pathway as a therapeutic target to compromise leukaemia stem-cell function in patients with IDHWTTET2WT AML.
  •  
Skapa referenser, mejla, bekava och länka
Åtkomst
fritt online (59)
Typ av publikation
tidskriftsartikel (1127)
forskningsöversikt (11)
annan publikation (10)
recension (9)
Typ av innehåll
refereegranskat (1024)
övrigt vetenskapligt (254)
populärvet., debatt m.m. (9)
Författare/redaktör
Collins, Francis S. (23)
Chasman, Daniel I., (21)
Ahlberg, Per E., (20)
Thorleifsson, Gudmar (20)
Hofman, Albert (19)
Harris, Tamara B. (19)
visa fler...
Gudnason, Vilmundur (18)
Ridker, Paul M., (18)
Mangino, Massimo (18)
Gieger, Christian (18)
Esko, Tonu (18)
Jackson, Anne U. (17)
Prokopenko, Inga (17)
Hayward, Caroline (17)
Caulfield, Mark J. (17)
Lindblad-Toh, Kersti ... (16)
Melander, Olle, (16)
Uitterlinden, Andre ... (16)
Salomaa, Veikko (16)
Lander, Eric S. (16)
Luan, Jian'an (16)
Hicks, Andrew A. (16)
Stringham, Heather M ... (16)
Amin, Najaf (15)
Teumer, Alexander (15)
Montgomery, Grant W. (15)
Wareham, Nicholas J (15)
Rose, Lynda M (15)
Feitosa, Mary F. (15)
Zhao, Jing Hua (15)
Perry, John R. B. (15)
Van Duijn, Cornelia ... (14)
Mohlke, Karen L (14)
Andersson, Leif, (14)
Wood, Andrew R. (14)
Sanna, Serena (14)
Campbell, Harry (14)
McArdle, Wendy L. (14)
Bergman, Richard N. (14)
Groop, Leif, (13)
Kuusisto, Johanna, (13)
McCarthy, Mark I (13)
Langenberg, Claudia (13)
Kaprio, Jaakko (13)
Samani, Nilesh J. (13)
Jarvelin, Marjo-Riit ... (13)
Hattersley, Andrew T (13)
Estrada, Karol (13)
Vedantam, Sailaja (13)
Ohlsson, Claes (13)
visa färre...
Lärosäte
Karolinska Institutet (242)
Uppsala universitet (240)
Lunds universitet (186)
Stockholms universitet (135)
Göteborgs universitet (86)
Umeå universitet (75)
visa fler...
Kungliga Tekniska Högskolan (54)
Chalmers tekniska högskola (45)
Linköpings universitet (43)
Sveriges Lantbruksuniversitet (43)
Linnéuniversitetet (13)
RISE (9)
Luleå tekniska universitet (7)
Örebro universitet (5)
Högskolan i Halmstad (4)
Mittuniversitetet (3)
Naturhistoriska riksmuseet (3)
Högskolan i Jönköping (2)
Södertörns högskola (2)
Högskolan i Skövde (2)
Högskolan Dalarna (2)
Mälardalens högskola (1)
Högskolan i Gävle (1)
visa färre...
Språk
Engelska (1152)
Odefinierat språk (3)
Svenska (1)
Forskningsämne (UKÄ/SCB)
Naturvetenskap (562)
Medicin och hälsovetenskap (204)
Samhällsvetenskap (35)
Teknik (34)
Lantbruksvetenskap (28)
Humaniora (17)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy