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11.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献12.
Limiting cheaters in mutualism: evidence from hybridization between mutualist and cheater yucca moths 总被引:3,自引:0,他引:3
Segraves KA Althoff DM Pellmyr O 《Proceedings. Biological sciences / The Royal Society》2005,272(1577):2195-2201
Mutualisms are balanced antagonistic interactions where both species gain a net benefit. Because mutualisms generate resources, they can be exploited by individuals that reap the benefits of the interaction without paying any cost. The presence of such 'cheaters' may have important consequences, yet we are only beginning to understand how cheaters evolve from mutualists and how their evolution may be curtailed within mutualistic lineages. The yucca-yucca moth pollination mutualism is an excellent model in this context as there have been two origins of cheating from within the yucca moth lineage. We used nuclear and mitochondrial DNA markers to examine genetic structure in a moth population where a cheater species is parapatric with a resident pollinator. The results revealed extensive hybridization between pollinators and cheaters. Hybrids were genetically intermediate to parental populations, even though all individuals in this population had a pollinator phenotype. The results suggest that mutualisms can be stable in the face of introgression of cheater genes and that the ability of cheaters to invade a given mutualism may be more limited than previously appreciated. 相似文献
13.
Comparative genomics of Brassica oleracea and Arabidopsis thaliana reveal gene loss, fragmentation, and dispersal after polyploidy 总被引:1,自引:0,他引:1 下载免费PDF全文
Town CD Cheung F Maiti R Crabtree J Haas BJ Wortman JR Hine EE Althoff R Arbogast TS Tallon LJ Vigouroux M Trick M Bancroft I 《The Plant cell》2006,18(6):1348-1359
14.
Interleukin (IL)-4, IL-10, and IL-13 are T-helper2 cell derived cytokines, which are known to suppress pro-inflammatory cytokine production. The biologically related IL-4 and IL-13 have an impact on the development of atopic inflammation, whereas IL-10 is mostly supposed to be involved in fibrotic disorders or inflammatory bowel disease. Their influence on the pathogenesis of severe lung injury is widely unknown. The expression of these proteins is mostly assumed to be restricted to leukocytic cells. Recently, some non-leukocytic cell types have been described to generate these mediators. In the present study, the constitutive cellular distribution pattern of IL-4, IL-13, IL-10, IL-4R alpha, STAT6 and IL-10R was elaborated by immunohistochemistry in the rat organism. Cytokine-specific regulation in lipopolysaccharide (LPS)-challenged rat lungs was investigated and constitutive expression was compared with human lungs. The study demonstrates strong expression of IL-4, IL-10, and IL-13 in different non-leukocytic cell types, especially in endothelial and epithelial cells in the entire rat organism. In concert with rat lung expression human lungs show strong similarities. Moreover, vascular LPS challenge of rat lungs generally demonstrates cell type-specific downregulation of the cytokines. We conclude that non-leukocytic cells in the organism play an important role in the regulation of organ-specific inflammatory reactions, especially in lungs. 相似文献
15.
Lisa-Marie Munter Anne Botev Luise Richter Peter W. Hildebrand Veit Althoff Christoph Weise Daniela Kaden Gerd Multhaup 《The Journal of biological chemistry》2010,285(28):21636-21643
The identification of hereditary familial Alzheimer disease (FAD) mutations in the amyloid precursor protein (APP) and presenilin-1 (PS1) corroborated the causative role of amyloid-β peptides with 42 amino acid residues (Aβ42) in the pathogenesis of AD. Although most FAD mutations are known to increase Aβ42 levels, mutations within the APP GxxxG motif are known to lower Aβ42 levels by attenuating transmembrane sequence dimerization. Here, we show that aberrant Aβ42 levels of FAD mutations can be rescued by GxxxG mutations. The combination of the APP-GxxxG mutation G33A with APP-FAD mutations yielded a constant 60% decrease of Aβ42 levels and a concomitant 3-fold increase of Aβ38 levels compared with the Gly33 wild-type as determined by ELISA. In the presence of PS1-FAD mutations, the effects of G33A were attenuated, apparently attributable to a different mechanism of PS1-FAD mutants compared with APP-FAD mutants. Our results contribute to a general understanding of the mechanism how APP is processed by the γ-secretase module and strongly emphasize the potential of the GxxxG motif in the prevention of sporadic AD as well as FAD. 相似文献
16.
Fouts DE Rasko DA Cer RZ Jiang L Fedorova NB Shvartsbeyn A Vamathevan JJ Tallon L Althoff R Arbogast TS Fadrosh DW Read TD Gill SR 《Journal of bacteriology》2006,188(9):3402-3408
The genetic relatedness of the Bacillus anthracis typing phages Gamma and Cherry was determined by nucleotide sequencing and comparative analysis. The genomes of these two phages were identical except at three variable loci, which showed heterogeneity within individual lysates and among Cherry, Wbeta, Fah, and four Gamma bacteriophage sequences. 相似文献
17.
Althoff EA Wang L Jiang L Giger L Lassila JK Wang Z Smith M Hari S Kast P Herschlag D Hilvert D Baker D 《Protein science : a publication of the Protein Society》2012,21(5):717-726
Enzyme catalysts of a retroaldol reaction have been generated by computational design using a motif that combines a lysine in a nonpolar environment with water-mediated stabilization of the carbinolamine hydroxyl and β-hydroxyl groups. Here, we show that the design process is robust and repeatable, with 33 new active designs constructed on 13 different protein scaffold backbones. The initial activities are not high but are increased through site-directed mutagenesis and laboratory evolution. Mutational data highlight areas for improvement in design. Different designed catalysts give different borohydride-reduced reaction intermediates, suggesting a distribution of properties of the designed enzymes that may be further explored and exploited. 相似文献
18.
19.
Testoni AF Althoff SL Nascimento AP Steiner-Souza F Sbalqueiro IJ 《Genetics and molecular biology》2010,33(3):479-485
Rhagomys rufescens (Rodentia: Sigmodontinae) is an endemic species of the Atlantic forest from Southern and Southeastern Brazil. Some authors consider Rhagomys as part of the tribe Thomasomyini; but its phylogenetic relationships remain unclear. Chromosomal studies on eight specimens of Rhagomys rufescens revealed a diploid number of 2n = 36 and a number of autosome arms FN = 50. GTG, CBG and Ag-NOR banding and CMA(3) /DAPI staining were performed on metaphase chromosomes. Eight biarmed and nine acrocentric pairs were found in the karyotype of this species. The X and Y chromosomes were both acrocentric. Most of the autosomes and the sex chromosomes showed positive C-bands in the pericentromeric region. The X chromosome showed an additional heterochromatic block in the proximal region of the long arm. Nucleolus organizer regions (NORs) were located in the pericentromeric region of three biarmed autosomes (pairs 4, 6 and 8) and in the telomeric region of the short arm of three acrocentrics (pairs 10, 12 and 17). CMA (3) /DAPI staining produced fluorescent signals in many autosomes, especially in pairs 4, 6, and 8. This study presents cytogenetic data of Rhagomys rufescens for the first time. 相似文献
20.
Yan Lu Shulin/SL Li Shiguo/SG Zhu Yabin/YB Gong Jun/J Shi Ling/ L Xu 《Biological procedures online》2017,19(1):2
DNA/RNA methylation plays an important role in lung cancer initiation and progression. Liquid biopsy makes use of cells, nucleotides and proteins released from tumor cells into body fluids to help with cancer diagnosis and prognosis. Methylation of circulating tumor DNA (ctDNA) has gained increasing attention as biomarkers for lung cancer. Here we briefly introduce the biological basis and detection method of ctDNA methylation, and review various applications of methylated DNA in body fluids in lung cancer screening, diagnosis, prognosis, monitoring and treatment prediction. We also discuss the emerging role of RNA methylation as biomarkers for cancer. 相似文献