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141.
Effects of household dynamics on resource consumption and biodiversity 总被引:41,自引:0,他引:41
Human population size and growth rate are often considered important drivers of biodiversity loss, whereas household dynamics are usually neglected. Aggregate demographic statistics may mask substantial changes in the size and number of households, and their effects on biodiversity. Household dynamics influence per capita consumption and thus biodiversity through, for example, consumption of wood for fuel, habitat alteration for home building and associated activities, and greenhouse gas emissions. Here we report that growth in household numbers globally, and particularly in countries with biodiversity hotspots (areas rich in endemic species and threatened by human activities), was more rapid than aggregate population growth between 1985 and 2000. Even when population size declined, the number of households increased substantially. Had the average household size (that is, the number of occupants) remained static, there would have been 155 million fewer households in hotspot countries in 2000. Reduction in average household size alone will add a projected 233 million additional households to hotspot countries during the period 2000-15. Rapid increase in household numbers, often manifested as urban sprawl, and resultant higher per capita resource consumption in smaller households pose serious challenges to biodiversity conservation. 相似文献
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Mao B Wu W Davidson G Marhold J Li M Mechler BM Delius H Hoppe D Stannek P Walter C Glinka A Niehrs C 《Nature》2002,417(6889):664-667
The Wnt family of secreted glycoproteins mediate cell cell interactions during cell growth and differentiation in both embryos and adults. Canonical Wnt signalling by way of the beta-catenin pathway is transduced by two receptor families. Frizzled proteins and lipoprotein-receptor-related proteins 5 and 6 (LRP5/6) bind Wnts and transmit their signal by stabilizing intracellular beta-catenin. Wnt/beta-catenin signalling is inhibited by the secreted protein Dickkopf1 (Dkk1), a member of a multigene family, which induces head formation in amphibian embryos. Dkk1 has been shown to inhibit Wnt signalling by binding to and antagonizing LRP5/6. Here we show that the transmembrane proteins Kremen1 and Kremen2 are high-affinity Dkk1 receptors that functionally cooperate with Dkk1 to block Wnt/beta-catenin signalling. Kremen2 forms a ternary complex with Dkk1 and LRP6, and induces rapid endocytosis and removal of the Wnt receptor LRP6 from the plasma membrane. The results indicate that Kremen1 and Kremen2 are components of a membrane complex modulating canonical Wnt signalling through LRP6 in vertebrates. 相似文献
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Alternative isoform regulation in human tissue transcriptomes 总被引:13,自引:0,他引:13
Wang ET Sandberg R Luo S Khrebtukova I Zhang L Mayr C Kingsmore SF Schroth GP Burge CB 《Nature》2008,456(7221):470-476
147.
Hung RJ McKay JD Gaborieau V Boffetta P Hashibe M Zaridze D Mukeria A Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Mates D Bencko V Foretova L Janout V Chen C Goodman G Field JK Liloglou T Xinarianos G Cassidy A McLaughlin J Liu G Narod S Krokan HE Skorpen F Elvestad MB Hveem K Vatten L Linseisen J Clavel-Chapelon F Vineis P Bueno-de-Mesquita HB Lund E Martinez C Bingham S Rasmuson T Hainaut P Riboli E Ahrens W Benhamou S Lagiou P Trichopoulos D Holcátová I Merletti F Kjaerheim K 《Nature》2008,452(7187):633-637
Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets. 相似文献
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Ramasri Sathanoori Paulina Bryl-Gorecka Christa E. Müller Laurie Erb Gary A. Weisman Björn Olde David Erlinge 《Cellular and molecular life sciences : CMLS》2017,74(4):731-746
Endothelial cells release ATP in response to fluid shear stress, which activates purinergic (P2) receptor-mediated signaling molecules including endothelial nitric oxide (eNOS), a regulator of vascular tone. While P2 receptor-mediated signaling in the vasculature is well studied, the role of P2Y2 receptors in shear stress-associated endothelial cell alignment, cytoskeletal alterations, and wound repair remains ill defined. To address these aspects, human umbilical vein endothelial cell (HUVEC) monolayers were cultured on gelatin-coated dishes and subjected to a shear stress of 1 Pa. HUVECs exposed to either P2Y2 receptor antagonists or siRNA showed impaired fluid shear stress-induced cell alignment, and actin stress fiber formation as early as 6 h. Similarly, when compared to cells expressing the P2Y2 Arg-Gly-Asp (RGD) wild-type receptors, HUVECs transiently expressing the P2Y2 Arg-Gly-Glu (RGE) mutant receptors showed reduced cell alignment and actin stress fiber formation in response to shear stress as well as to P2Y2 receptor agonists in static cultures. Additionally, we observed reduced shear stress-induced phosphorylation of focal adhesion kinase (Y397), and cofilin-1 (S3) with receptor knockdown as well as in cells expressing the P2Y2 RGE mutant receptors. Consistent with the role of P2Y2 receptors in vasodilation, receptor knockdown and overexpression of P2Y2 RGE mutant receptors reduced shear stress-induced phosphorylation of AKT (S473), and eNOS (S1177). Furthermore, in a scratched wound assay, shear stress-induced cell migration was reduced by both pharmacological inhibition and receptor knockdown. Together, our results suggest a novel role for P2Y2 receptor in shear stress-induced cytoskeletal alterations in HUVECs. 相似文献
150.
Haiman CA Chen GK Vachon CM Canzian F Dunning A Millikan RC Wang X Ademuyiwa F Ahmed S Ambrosone CB Baglietto L Balleine R Bandera EV Beckmann MW Berg CD Bernstein L Blomqvist C Blot WJ Brauch H Buring JE Carey LA Carpenter JE Chang-Claude J Chanock SJ Chasman DI Clarke CL Cox A Cross SS Deming SL Diasio RB Dimopoulos AM Driver WR Dünnebier T Durcan L Eccles D Edlund CK Ekici AB Fasching PA Feigelson HS Flesch-Janys D Fostira F Försti A Fountzilas G 《Nature genetics》2011,43(12):1210-1214
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. 相似文献