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21.
22.
Don't judge species on their origins 总被引:1,自引:0,他引:1
23.
Extended megadroughts in the southwestern United States during Pleistocene interglacials 总被引:1,自引:0,他引:1
Fawcett PJ Werne JP Anderson RS Heikoop JM Brown ET Berke MA Smith SJ Goff F Donohoo-Hurley L Cisneros-Dozal LM Schouten S Sinninghe Damsté JS Huang Y Toney J Fessenden J WoldeGabriel G Atudorei V Geissman JW Allen CD 《Nature》2011,470(7335):518-521
The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ~2?°C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6?°C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase. 相似文献
24.
25.
Edouard T Montagner A Dance M Conte F Yart A Parfait B Tauber M Salles JP Raynal P 《Cellular and molecular life sciences : CMLS》2007,64(13):1585-1590
Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes.
Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by
mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis
of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1,
Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated
by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative
effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK
activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the
possibility that LS mutations may not simply exhibit dominant negative activity.
Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007 相似文献
26.
Péterfy M Ben-Zeev O Mao HZ Weissglas-Volkov D Aouizerat BE Pullinger CR Frost PH Kane JP Malloy MJ Reue K Pajukanta P Doolittle MH 《Nature genetics》2007,39(12):1483-1487
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia. 相似文献
27.
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
28.
Baumann P Thiele W Cremers N Muppala S Krachulec J Diefenbacher M Kassel O Mudduluru G Allgayer H Frame M Sleeman JP 《Cellular and molecular life sciences : CMLS》2012,69(3):435-448
Expression of the glycosylphosphatidylinositol-anchored membrane protein CD24 correlates with a poor prognosis for many human cancers, and in experimental tumors can promote metastasis. However, the mechanism by which CD24 contributes to tumor progression remains unclear. Here we report that in MTLy breast cancer cells CD24 interacts with and augments the kinase activity of c-src, a protein strongly implicated in promoting invasion and metastasis. This occurs within and is dependent upon intact lipid rafts. CD24-augmented c-src kinase activity increased formation of focal adhesion complexes, accelerated phosphorylation of FAK and paxillin and consequently enhanced integrin-mediated adhesion. Loss and gain of function approaches showed that c-src activity is necessary and sufficient to mediate the effects of CD24 on integrin-dependent adhesion and cell spreading, as well as on invasion. Together these results indicate that c-src is a CD24-activated mediator that promotes integrin-mediated adhesion and invasion, and suggest a mechanism by which CD24 might contribute to tumor progression through stimulating the activity of c-src or another member of the Src family. 相似文献
29.
Elia J Glessner JT Wang K Takahashi N Shtir CJ Hadley D Sleiman PM Zhang H Kim CE Robison R Lyon GJ Flory JH Bradfield JP Imielinski M Hou C Frackelton EC Chiavacci RM Sakurai T Rabin C Middleton FA Thomas KA Garris M Mentch F Freitag CM Steinhausen HC Todorov AA Reif A Rothenberger A Franke B Mick EO Roeyers H Buitelaar J Lesch KP Banaschewski T Ebstein RP Mulas F Oades RD Sergeant J Sonuga-Barke E Renner TJ Romanos M Romanos J Warnke A Walitza S Meyer J Pálmason H Seitz C Loo SK Smalley SL 《Nature genetics》2012,44(1):78-84
Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ~10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts. 相似文献
30.
Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses 总被引:8,自引:0,他引:8
RJ O'Connell MR Thon S Hacquard SG Amyotte J Kleemann MF Torres U Damm EA Buiate L Epstein N Alkan J Altmüller L Alvarado-Balderrama CA Bauser C Becker BW Birren Z Chen J Choi JA Crouch JP Duvick MA Farman P Gan D Heiman B Henrissat RJ Howard M Kabbage C Koch B Kracher Y Kubo AD Law MH Lebrun YH Lee I Miyara N Moore U Neumann K Nordström DG Panaccione R Panstruga M Place RH Proctor D Prusky G Rech R Reinhardt JA Rollins S Rounsley CL Schardl DC Schwartz N Shenoy K Shirasu UR Sikhakolli K Stüber 《Nature genetics》2012,44(9):1060-1065