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991.
Laura J. Rasmussen-Torvik James S. Pankow David R. JacobsJr Julia Steinberger Antoinette Moran Alan R. Sinaiko 《Human genetics》2009,125(1):21-28
Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2)
genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag
SNPs in these genes with insulin sensitivity was examined in a cohort of adolescents and their parents. Probands and siblings
(n = 441, mean age = 17.9 years) were recruited along with their parents (n = 262, mean age = 47.9 years). Typed SNPs included 21 SNPs in ADIPOQ, 7 SNPs in ADIPOR1, and 13 SNPs in ADIPOR2. Mixed model
linear regression was used to test the association of SNPs with euglycemic-clamp derived insulin sensitivity. All analyses
were stratified by race. After corrections to account for multiple testing and the linkage disequilibrium structure of the
genes, one SNP in the ADIPOQ gene (rs822393) was significantly associated with insulin sensitivity in white subjects. In whites,
six SNPs in ADIPOQ, one SNP in ADIPOR1 and one SNP in ADIPOR2 were associated with insulin sensitivity at the P < 0.05 level. In African Americans, two SNPs in ADIPOR1 were associated with insulin sensitivity at the P < 0.05 level. These results suggest that a variant in the ADIPOQ gene influences levels of insulin sensitivity and age may
modify the effects of this variant. There are several other variants in ADIPOQ, ADIPOR1, and ADIPOR2 that may influence insulin
sensitivity and these variants should be further investigated in other populations.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
992.
993.
Laura Owens Scott Simanski Christopher Squire Anthony Smith Jeff Cartzendafner Valerie Cavett Jennifer Caldwell Busby Trey Sato Nagi G. Ayad 《The Journal of biological chemistry》2010,285(9):6761-6769
Cell cycle progression is dependent upon coordinate regulation of kinase and proteolytic pathways. Inhibitors of cell cycle transitions are degraded to allow progression into the subsequent cell cycle phase. For example, the tyrosine kinase and Cdk1 inhibitor Wee1 is degraded during G2 and mitosis to allow mitotic progression. Previous studies suggested that the N terminus of Wee1 directs Wee1 destruction. Using a chemical mutagenesis strategy, we report that multiple regions of Wee1 control its destruction. Most notably, we find that the activation domain of the Wee1 kinase is also required for its degradation. Mutations in this domain inhibit Wee1 degradation in somatic cell extracts and in cells without affecting the overall Wee1 structure or kinase activity. More broadly, these findings suggest that kinase activation domains may be previously unappreciated sites of recognition by the ubiquitin proteasome pathway. 相似文献
994.
Zanek MC Reyes CA Cervera M Peña EJ Velázquez K Costa N Plata MI Grau O Peña L García ML 《Plant cell reports》2008,27(1):57-66
Citrus psorosis is a serious viral disease affecting citrus trees in many countries. Its causal agent is Citrus psorosis virus (CPsV), the type member of genus Ophiovirus. CPsV infects most important citrus varieties, including oranges, mandarins and grapefruits, as well as hybrids and citrus
relatives used as rootstocks. Certification programs have not been sufficient to control the disease and no sources of natural resistance have been found.
Pathogen-derived resistance (PDR) can provide an efficient alternative to control viral diseases in their hosts. For this
purpose, we have produced 21 independent lines of sweet orange expressing the coat protein gene of CPsV and five of them were
challenged with the homologous CPV 4 isolate. Two different viral loads were evaluated to challenge the transgenic plants,
but so far, no resistance or tolerance has been found in any line after 1 year of observations. In contrast, after inoculation
all lines showed characteristic symptoms of psorosis in the greenhouse. The transgenic lines expressed low and variable amounts
of the cp gene and no correlation was found between copy number and transgene expression. One line contained three copies of the cp gene, expressed low amounts of the mRNA and no coat protein. The ORF was cytosine methylated suggesting a PTGS mechanism,
although the transformant failed to protect against the viral load used. Possible causes for the failed protection against
the CPsV are discussed. 相似文献
995.
Vertical distribution of methane metabolism in microbial mats of the Great Sippewissett Salt Marsh 总被引:3,自引:0,他引:3
Methane metabolism was investigated with respect to depth in intertidal microbial mats of the Great Sippewissett Salt Marsh, Massachusetts. Although sulfate-reducing organisms dominate anaerobic carbon consumption in marine microbial mats, methanogens persist and their activity varies vertically and temporally in the mat system. In the Sippewissett mats, potential methane production for all mat layers was higher in the spring (17.2 ± 4.5 nmol CH4 cm−2 day−1 ) than in the fall (3.0 ± 1.1 nmol CH4 cm−2 day−1 ) and maximal rates were consistently observed in proximity to the chemocline (5–10 mm depth). The methane flux from the mat surface did not vary appreciably over time due to the ability of methanotrophic activity to limit net methane production. Evidence indicates that both aerobic and anaerobic oxidation of methane occurs in this system. The importance of H2 as a substrate for methanogenesis appeared to be the greatest at the mat surface (0–10 mm), and the proportion of methylotrophic methanogens generally increased with depth. These results suggest that both non-equilibrium H2 dynamics and the use of non-competitive substrates permit coexistence of methanogens and sulfate-reducing organisms in the mat system. 相似文献
996.
Thermodynamic parameters are reported for duplex formation of 40 self-complementary RNA duplexes containing wobble terminal base pairs with all possible 3′ single and double-nucleotide overhangs, mimicking the structures of short interfering RNAs (siRNA) and microRNAs (miRNA). Based on nearest neighbor analysis, the addition of a single 3′ dangling nucleotide increases the stability of duplex formation up to 1 kcal/mol in a sequence-dependent manner. The addition of a second dangling nucleotide increases the stability of duplexes closed with wobble base pairs in an idiosyncratic manner. The results allow for the development of a nearest neighbor model, which improves the predication of free energy and melting temperature for duplexes closed by wobble base pairs with 3′ single or double-nucleotide overhangs. Phylogenetic analysis of naturally occurring miRNAs was performed. Selection of the effector miR strand of the mature miRNA duplex appears to be dependent on the orientation of the GU closing base pair rather than the identity of the 3′ double-nucleotide overhang. Thermodynamic parameters for the 5′ single terminal overhangs adjacent to wobble closing base pairs are also presented. 相似文献
997.
998.
Laura Dyer Pamela Lockyer Yaxu Wu Arnab Saha Chelsea Cyr Martin Moser Xinchun Pi Cam Patterson 《PloS one》2015,10(9)
Formation of the cardiac valves is an essential component of cardiovascular development. Consistent with the role of the bone morphogenetic protein (BMP) signaling pathway in cardiac valve formation, embryos that are deficient for the BMP regulator BMPER (BMP-binding endothelial regulator) display the cardiac valve anomaly mitral valve prolapse. However, how BMPER deficiency leads to this defect is unknown. Based on its expression pattern in the developing cardiac cushions, we hypothesized that BMPER regulates BMP2-mediated signaling, leading to fine-tuned epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. In the BMPER-/- embryo, EMT is dysregulated in the atrioventricular and outflow tract cushions compared with their wild-type counterparts, as indicated by a significant increase of Sox9-positive cells during cushion formation. However, proliferation is not impaired in the developing BMPER-/- valves. In vitro data show that BMPER directly binds BMP2. In cultured endothelial cells, BMPER blocks BMP2-induced Smad activation in a dose-dependent manner. In addition, BMP2 increases the Sox9 protein level, and this increase is inhibited by co-treatment with BMPER. Consistently, in the BMPER-/- embryos, semi-quantitative analysis of Smad activation shows that the canonical BMP pathway is significantly more active in the atrioventricular cushions during EMT. These results indicate that BMPER negatively regulates BMP-induced Smad and Sox9 activity during valve development. Together, these results identify BMPER as a regulator of BMP2-induced cardiac valve development and will contribute to our understanding of valvular defects. 相似文献
999.
Schaeffer SW Bhutkar A McAllister BF Matsuda M Matzkin LM O'Grady PM Rohde C Valente VL Aguadé M Anderson WW Edwards K Garcia AC Goodman J Hartigan J Kataoka E Lapoint RT Lozovsky ER Machado CA Noor MA Papaceit M Reed LK Richards S Rieger TT Russo SM Sato H Segarra C Smith DR Smith TF Strelets V Tobari YN Tomimura Y Wasserman M Watts T Wilson R Yoshida K Markow TA Gelbart WM Kaufman TC 《Genetics》2008,179(3):1601-1655
The sequencing of the 12 genomes of members of the genus Drosophila was taken as an opportunity to reevaluate the genetic and physical maps for 11 of the species, in part to aid in the mapping of assembled scaffolds. Here, we present an overview of the importance of cytogenetic maps to Drosophila biology and to the concepts of chromosomal evolution. Physical and genetic markers were used to anchor the genome assembly scaffolds to the polytene chromosomal maps for each species. In addition, a computational approach was used to anchor smaller scaffolds on the basis of the analysis of syntenic blocks. We present the chromosomal map data from each of the 11 sequenced non-Drosophila melanogaster species as a series of sections. Each section reviews the history of the polytene chromosome maps for each species, presents the new polytene chromosome maps, and anchors the genomic scaffolds to the cytological maps using genetic and physical markers. The mapping data agree with Muller's idea that the majority of Drosophila genes are syntenic. Despite the conservation of genes within homologous chromosome arms across species, the karyotypes of these species have changed through the fusion of chromosomal arms followed by subsequent rearrangement events. 相似文献
1000.
Howden R Liu E Miller-DeGraff L Keener HL Walker C Clark JA Myers PH Rouse DC Wiltshire T Kleeberger SR 《American journal of physiology. Heart and circulatory physiology》2008,295(1):H59-H68
Recent studies have suggested a genetic component to heart rate (HR) and HR variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Electrocardiogram data were recorded from 30 strains of inbred mice and 29 RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low-frequency (LF) and high-frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genomewide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated HR 1 (Hr1)]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated HRV-high-frequency 1 (Hrvhf1)] and three suggestive QTLs on chromosomes 2, 11 and 15. In conclusion, the results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. A lack of correlation between HR and HRV phenotypes in some inbred strains suggests that different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest. 相似文献