排序方式: 共有64条查询结果,搜索用时 15 毫秒
41.
Kers JA Wach MJ Krasnoff SB Widom J Cameron KD Bukhalid RA Gibson DM Crane BR Loria R 《Nature》2004,429(6987):79-82
Nitric oxide (NO) is a potent intercellular signal in mammals that mediates key aspects of blood pressure, hormone release, nerve transmission and the immune response of higher organisms. Proteins homologous to full-length mammalian nitric oxide synthases (NOSs) are found in lower multicellular organisms. Recently, genome sequencing has shown that some bacteria contain genes coding for truncated NOS proteins; this is consistent with reports of NOS-like activities in bacterial extracts. Biological functions for bacterial NOSs are unknown, but have been presumed to be analogous to their role in mammals. Here we describe a gene in the plant pathogen Streptomyces turgidiscabies that encodes a NOS homologue, and we reveal its role in nitrating a dipeptide phytotoxin required for plant pathogenicity. High similarity between bacterial NOSs indicates a general function in biosynthetic nitration; thus, bacterial NOSs constitute a new class of enzymes. Here we show that the primary function of Streptomyces NOS is radically different from that of mammalian NOS. Surprisingly, mammalian NO signalling and bacterial biosynthetic nitration share an evolutionary origin. 相似文献
42.
Lindsey T. Brinton Hillary S. Sloane Mark Kester Kimberly A. Kelly 《Cellular and molecular life sciences : CMLS》2015,72(4):659-671
Exosomes offer new insight into cancer biology with both diagnostic and therapeutic implications. Because of their cell-to-cell communication, exosomes influence tumor progression, metastasis, and therapeutic efficacy. They can be isolated from blood and other bodily fluids to reveal disease processes occurring within the body, including cancerous growth. In addition to being a reservoir of cancer biomarkers, they can be re-engineered to reinstate tumor immunity. Tumor exosomes interact with various cells of the microenvironment to confer tumor-advantageous changes that are responsible for stromal activation, induction of the angiogenic switch, increased vascular permeability, and immune escape. Exosomes also contribute to metastasis by aiding in the epithelial-to-mesenchymal transition and formation of the pre-metastatic niche. Furthermore, exosomes protect tumor cells from the cytotoxic effects of chemotherapy drugs and transfer chemoresistance properties to nearby cells. Thus, exosomes are essential to many lethal elements of cancer and it is important to understand their biogenesis and role in cancer. 相似文献
43.
Laurie CC Laurie CA Rice K Doheny KF Zelnick LR McHugh CP Ling H Hetrick KN Pugh EW Amos C Wei Q Wang LE Lee JE Barnes KC Hansel NN Mathias R Daley D Beaty TH Scott AF Ruczinski I Scharpf RB Bierut LJ Hartz SM Landi MT Freedman ND Goldin LR Ginsburg D Li J Desch KC Strom SS Blot WJ Signorello LB Ingles SA Chanock SJ Berndt SI Le Marchand L Henderson BE Monroe KR Heit JA de Andrade M Armasu SM Regnier C Lowe WL Hayes MG Marazita ML Feingold E Murray JC Melbye M Feenstra B Kang JH Wiggs JL 《Nature genetics》2012,44(6):642-650
We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18). 相似文献
44.
Ferreira MA O'Donovan MC Meng YA Jones IR Ruderfer DM Jones L Fan J Kirov G Perlis RH Green EK Smoller JW Grozeva D Stone J Nikolov I Chambert K Hamshere ML Nimgaonkar VL Moskvina V Thase ME Caesar S Sachs GS Franklin J Gordon-Smith K Ardlie KG Gabriel SB Fraser C Blumenstiel B Defelice M Breen G Gill M Morris DW Elkin A Muir WJ McGhee KA Williamson R MacIntyre DJ MacLean AW St CD Robinson M Van Beck M Pereira AC Kandaswamy R McQuillin A Collier DA Bass NJ Young AH Lawrence J Ferrier IN 《Nature genetics》2008,40(9):1056-1058
To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder. 相似文献
45.
Sanna S Jackson AU Nagaraja R Willer CJ Chen WM Bonnycastle LL Shen H Timpson N Lettre G Usala G Chines PS Stringham HM Scott LJ Dei M Lai S Albai G Crisponi L Naitza S Doheny KF Pugh EW Ben-Shlomo Y Ebrahim S Lawlor DA Bergman RN Watanabe RM Uda M Tuomilehto J Coresh J Hirschhorn JN Shuldiner AR Schlessinger D Collins FS Davey Smith G Boerwinkle E Cao A Boehnke M Abecasis GR Mohlke KL 《Nature genetics》2008,40(2):198-203
46.
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
47.
Nath SK Han S Kim-Howard X Kelly JA Viswanathan P Gilkeson GS Chen W Zhu C McEver RP Kimberly RP Alarcón-Riquelme ME Vyse TJ Li QZ Wakeland EK Merrill JT James JA Kaufman KM Guthridge JM Harley JB 《Nature genetics》2008,40(2):152-154
We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 x 10(-17), odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 x 10(-22)). The genetic association between ITGAM and SLE implicates the alpha(M)beta2-integrin adhesion pathway in disease development. 相似文献
48.
Many desert perennials are long-lived, but there are few data on ages or population structures of desert plants. We used 2 methods to estimate ages of a population of Yucca brevifolia (Joshua tree) in southwestern Utah from a 14-year census of plant sizes. Plant height at the 1st census ranged from 0.08 m to 6.0 m, and trees grew in height at a mean rate of 3.75 cm ? yr -1 . Plants also increased slowly in basal diameter (0.142 cm ? yr -1 ) and branch length (0.024 m ? yr -1 ), but basal diameter varied greatly from year to year, with many plants decreasing in diameter between sequential censuses. Forms of a nonlinear growth equation (the Richards function) did not fit the data on growth in height, but a simple linear relationship fit the data well. Using height as a linear predictor of age, we estimated that ages of a sample of 69 Joshua trees ranged from 300 years old, with 75% of the trees between 20 and 100 years and 11% over 150 years old. These data support the assumption that Joshua trees are indeed long-lived. 相似文献
49.
Kimberly Vanhees Indira G. C. Vonhögen Frederik J. van Schooten Roger W. L. Godschalk 《Cellular and molecular life sciences : CMLS》2014,71(2):271-285
The research field of fetal programming has developed tremendously over the years and increasing knowledge suggests that both maternal and paternal unbalanced diet can have long-lasting effects on the health of offspring. Studies implicate that macronutrients play an important role in fetal programming, although the importance of micronutrients is also becoming increasingly apparent. Folic acid and vitamins B2, B6 and B12 are essential for one-carbon metabolism and are involved in DNA methylation. They can therefore influence the programming of the offspring’s epigenome. Also, other micronutrients such as vitamins A and C, iron, chromium, zinc and flavonoids play a role in fetal programming. Since it is estimated that approximately 78 % of pregnant women in the US take vitamin supplements during pregnancy, more attention should be given to the long-term effects of these supplements on offspring. In this review we address several different studies which illustrate that an unbalanced diet prior and during pregnancy, regarding the intake of micronutrients of both mother and father, can have long-lasting effects on the health of adult offspring. 相似文献