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881.
为了研究地下圆形衬砌洞室在入射平面SV波和Rayleigh波作用下的动应力集中问题,利用波函数展开法,求解出三维条件下的级数解。当衬砌与半空间介质相同时,级数解将退化为无衬砌时的结果。级数解为进一步定量分析衬砌洞室对入射平面SV波和Rayleigh波的动力集中提供了理论基础。 相似文献
882.
L. Lee Grismer Perry L. Wood Jr Myint Kyaw Thura Thaw Zin Evan S. H. Quah Matthew L. Murdoch 《Journal of Natural History》2018,52(13-16):881-915
ABSTRACTA phylogenetic taxonomy of the gekkonid genus Hemiphyllodactylus based on molecular, morphological, and ecological data recovered 28 species, including three new species from the upland regions of the Shan Plateau in eastern Myanmar. Hemiphyllodactylus linnwayensis sp. nov. is a forest-adapted species that may also be a human commensal and H. montawaensis sp. nov. and H. tonywhitteni sp. nov. are karst forest-adapted species. The discovery of three new species from montane regions in eastern Myanmar extends the distribution of a larger monophyletic group of Hemiphyllodactylus westward to the eastern edge of the Ayeyrawady Basin through a series of semi-contiguous, parallel mountain ranges originating in western China and northern Thailand. The discovery of the karst forest-adapted H. montawaensis sp. nov. and H. tonywhitteni sp. nov. further emphasizes the unrealized herpetological diversity endemic to karst ecosystems and the need for increased field work throughout such habitats in South-East Asia.www.zoobank.org/urn:lsid:zoobank.org:pub:E42FA075-E8E0-4005-98AB-12E8D5F23A07 相似文献
883.
Hsu SP Ho PY Juan SH Liang YC Lee WS 《Cellular and molecular life sciences : CMLS》2008,65(23):3839-3850
Previous studies have shown that progesterone inhibits endothelial cell proliferation through a nuclear receptor-mediated
mechanism. Here, we further demonstrate that progesterone at physiologic levels (5 – 500 nM) dose- and time-dependently inhibited
DNA synthesis of cultured human umbilical vein endothelial cells (HUVEC). The mRNA and protein levels of p21, p27, and p53
in HUVEC were increased by progesterone. The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased
in the progesterone-treated HUVEC. The progesterone-inhibited [3H]thymidine incorporation was completely blocked when the
expressions of p21 and p27 were knocked-down together. Transfection of HUVEC with dominant negative p53 cDNA prevented the
progesterone-induced increases in p21 and p27 promoter activity and protein level, decreases in thymidine incorporation, and
capillary-like tube formation. Matrigel angiogenesis assay in mice demonstrated the antiangiogenic effect of progesterone
in vivo. These findings demonstrate for the first time that progesterone inhibited endothelial cell proliferation through a p53-dependent
pathway.
Received 28 July 2008; received after revision 25 September 2008; accepted 26 September 2008 相似文献
884.
Romeo S Kozlitina J Xing C Pertsemlidis A Cox D Pennacchio LA Boerwinkle E Cohen JC Hobbs HH 《Nature genetics》2008,40(12):1461-1465
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ancestry groups. To identify genetic variants contributing to differences in hepatic fat content, we carried out a genome-wide association scan of nonsynonymous sequence variations (n = 9,229) in a population comprising Hispanic, African American and European American individuals. An allele in PNPLA3 (rs738409[G], encoding I148M) was strongly associated with increased hepatic fat levels (P = 5.9 x 10(-10)) and with hepatic inflammation (P = 3.7 x 10(-4)). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was more than twofold higher in PNPLA3 rs738409[G] homozygotes than in noncarriers. Resequencing revealed another allele of PNPLA3 (rs6006460[T], encoding S453I) that was associated with lower hepatic fat content in African Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD. 相似文献
885.
Yasuda K Miyake K Horikawa Y Hara K Osawa H Furuta H Hirota Y Mori H Jonsson A Sato Y Yamagata K Hinokio Y Wang HY Tanahashi T Nakamura N Oka Y Iwasaki N Iwamoto Y Yamada Y Seino Y Maegawa H Kashiwagi A Takeda J Maeda E Shin HD Cho YM Park KS Lee HK Ng MC Ma RC So WY Chan JC Lyssenko V Tuomi T Nilsson P Groop L Kamatani N Sekine A Nakamura Y Yamamoto K Yoshida T Tokunaga K Itakura M Makino H Nanjo K Kadowaki T Kasuga M 《Nature genetics》2008,40(9):1092-1097
We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries. 相似文献
886.
Korn JM Kuruvilla FG McCarroll SA Wysoker A Nemesh J Cawley S Hubbell E Veitch J Collins PJ Darvishi K Lee C Nizzari MM Gabriel SB Purcell S Daly MJ Altshuler D 《Nature genetics》2008,40(10):1253-1260
Accurate and complete measurement of single nucleotide (SNP) and copy number (CNV) variants, both common and rare, will be required to understand the role of genetic variation in disease. We present Birdsuite, a four-stage analytical framework instantiated in software for deriving integrated and mutually consistent copy number and SNP genotypes. The method sequentially assigns copy number across regions of common copy number polymorphisms (CNPs), calls genotypes of SNPs, identifies rare CNVs via a hidden Markov model (HMM), and generates an integrated sequence and copy number genotype at every locus (for example, including genotypes such as A-null, AAB and BBB in addition to AA, AB and BB calls). Such genotypes more accurately depict the underlying sequence of each individual, reducing the rate of apparent mendelian inconsistencies. The Birdsuite software is applied here to data from the Affymetrix SNP 6.0 array. Additionally, we describe a method, implemented in PLINK, to utilize these combined SNP and CNV genotypes for association testing with a phenotype. 相似文献
887.
International Consortium for Systemic Lupus Erythematosus Genetics 《Nature genetics》2008,40(2):204-210
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE. 相似文献
888.
STAR Consortium Saar K Beck A Bihoreau MT Birney E Brocklebank D Chen Y Cuppen E Demonchy S Dopazo J Flicek P Foglio M Fujiyama A Gut IG Gauguier D Guigo R Guryev V Heinig M Hummel O Jahn N Klages S Kren V Kube M Kuhl H Kuramoto T Kuroki Y Lechner D Lee YA Lopez-Bigas N Lathrop GM Mashimo T Medina I Mott R Patone G Perrier-Cornet JA Platzer M Pravenec M Reinhardt R Sakaki Y Schilhabel M Schulz H Serikawa T Shikhagaie M Tatsumoto S Taudien S Toyoda A Voigt B Zelenika D Zimdahl H Hubner N 《Nature genetics》2008,40(5):560-566
The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies. 相似文献
889.
Chih-Cheng Chang Shih-Ying Tsai Heng Lin Hsiao-Fen Li Yi-Hsuan Lee Ying Chou Chih-Yu Jen Shu-Hui Juan 《Cellular and molecular life sciences : CMLS》2009,66(19):3193-3205
We previously demonstrated the antiproliferative and antiangiogenic effects of 3-methylcholanthrene (3MC), an aryl-hydrocarbon
receptor (AhR) agonist, in human umbilical vascular endothelial cells (HUVECs). Herein, we unraveled its molecular mechanisms
in inhibiting HUVEC motility. 3MC down-regulated FAK, but up-regulated RhoA, which was rescued by AhR knockdown. It led us
to identify novel AhR binding sites in the FAK/RhoA promoters. Additionally, 3MC increased RhoA activity via suppression of
a negative feedback pathway of FAK/p190RhoGAP. With an increase in membrane-bound RhoA, subsequent stress fiber and focal
adhesion complex formation was observed in 3MC-treated cells, and this was reversed by a RhoA inhibitor and AhR antagonists.
Notably, these compounds significantly reversed 3MC-mediated anti-migration in a transwell assay. The in vitro findings were
further confirmed using an animal model of Matrigel formation in Balb/c mice. Collectively, AhR’s genomic regulation of FAK/RhoA,
together with RhoA activation, is ascribable to the anti-migration effect of 3MC in HUVECs. 相似文献
890.
C.-J. Chang P.-H. Yin D.-M. Yang C.-H. Wang W.-Y. Hung C.-W. Chi Y.-H. Wei H.-C. Lee 《Cellular and molecular life sciences : CMLS》2009,66(10):1755-1765
The aim of this study was to investigate the contribution of mitochondrial dysfunction to chemoresistance and migration of
hepatoma cells. We found that inhibition of mitochondrial respiration and mitochondrial DNA (mtDNA) depletion resulted in
induction of amphiregulin (AR) expression in HepG2 cells. Upon oligomycin treatment of HepG2 cells, the cytosolic Ca2+ was significantly raised after 30 min, and the intracellular level of reactive oxygen species (ROS) was elevated 2.2-fold
after 4 h. Moreover, the condition medium of oligomycin-treated HepG2 cells was found to stimulate the migration of SK-Hep-1
cells. On the other hand, oligomycin-induced cisplatin-resistance and cell migration of HepG2 cells were attenuated by AR-specific
RNA interference (#L-017435, Dharmacon) and a neutralizing antibody (MAB262, R&D Systems), respectively. Together, these findings
suggest that mitochondrial dysfunction induced Ca2+ mobilization, and ROS overproduction, which modulated the chemo-resistance and migration of hepatoma cells through the induction
and activation of AR.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Y.-H. Wei, H.-C. Lee: These authors contribute equally to this work.
Received 02 December 2008; received after revision 16 March 2009; accepted 17 March 2009 相似文献