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61.
Joellen M. Schildkraut Edwin S. Iversen Melanie A. Wilson Merlise A. Clyde Patricia G. Moorman Rachel T. Palmieri Regina Whitaker Rex C. Bentley Jeffrey R. Marks Andrew Berchuck 《PloS one》2010,5(4)
Background
We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study.Methods/Principal Findings
The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)per allele = 0.66; 95% credible interval (CI) = 0.44–1.00) and rs6005835 (median ORper allele = 0.69; 95% CI = 0.53–0.91) in CHEK2, rs2078486 (median ORper allele = 1.65; 95% CI = 1.21–2.25) and rs12951053 (median ORper allele = 1.65; 95% CI = 1.20–2.26) in TP53, rs411697 (median OR rare homozygote = 0.53; 95% CI = 0.35 – 0.79) in BACH1 and rs10131 (median OR rare homozygote = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study.Conclusions/Significance
Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results. 相似文献62.
Two panels of hybridomas were produced that secreted monoclonal antibodies (MAbs) against recombinant DNA-derived human interleukin 3 and interleukin 4 (rhIL-3 and rhIL-4). From each panel, sensitive immunoradiometric assays (IRMAs) were developed which were capable of detecting the recombinant molecule used as the immunogen but were unable to recognize natural or other recombinant forms of the same cytokine. Subsequent studies using the MAbs from each panel showed that a number of the MAbs appeared only to recognize that particular recombinant molecule used as immunogen, with little or no binding to other recombinant forms of the molecule. By using MAbs that were found to be unrestricted in their recognition for different recombinant forms of the cytokines, it was possible to develop an IRMA for IL-4 that was capable of detecting natural IL-4 as well as all the recombinant forms equally. An IRMA was also developed for IL-3 but was not of equivalent sensitivity in detecting the different recombinant forms of IL-3 used in the study. The recombinant DNA-derived cytokine molecules used to raise the two panels of MAbs contained amino acid substitutions relative to the natural sequences, and these findings indicate that caution should be exercised when using immunoassays to estimate natural sequence molecules if antibodies raised to modified rDNA-derived molecules are used. 相似文献
63.
Joseph Henson Thomas Yates Charlotte L. Edwardson Kamlesh Khunti Duncan Talbot Laura J. Gray Thomas M. Leigh Patrice Carter Melanie J. Davies 《PloS one》2013,8(10)
Background
Sedentary behaviour has been identified as a distinct risk factor for several health outcomes. Nevertheless, little research has been conducted into the underlying mechanisms driving these observations. This study aimed to investigate the association of objectively measured sedentary time and breaks in sedentary time with markers of chronic low-grade inflammation and adiposity in a population at a high risk of type 2 diabetes mellitus.Methods
This study reports data from an ongoing diabetes prevention programme conducted in Leicestershire, UK. High risk individuals were recruited from 10 primary care practices. Sedentary time (<25counts per 15s) was measured using Actigraph GT3X accelerometers (15s epochs). A break was considered as any interruption in sedentary time (≥25counts per 15s). Biochemical outcomes included interleukin-6 (IL-6), C-reactive protein (CRP), leptin, adiponectin and leptin:adiponectin ratio (LAR). A sensitivity analysis investigated whether results were affected by removing participants with a CRP level >10 mg/L, as this can be indicative of acute inflammation.Results
558 participants (age = 63.6±7.7years; male = 64.7%) had complete adipokine and accelerometer data. Following adjustment for various confounders, sedentary time was detrimentally associated with CRP (β = 0.176±0.057, p = 0.002), IL-6 (β = 0.242±0.056, p = <0.001), leptin (β = 0.146±0.043, p = <0.001) and LAR (β = 0.208±0.052, p = <0.001). Associations were attenuated after further adjustment for moderate-to-vigorous physical activity (MVPA) with only IL-6 (β = 0.231±0.073, p = 0.002) remaining significant; this result was unaffected after further adjustment for body mass index and glycosylated haemoglobin (HbA1c). Similarly, breaks in sedentary time were significantly inversely associated with IL-6 (β = −0.094±0.047, p = 0.045) and leptin (β = −0.075±0.037, p = 0.039); however, these associations were attenuated after adjustment for accelerometer derived variables. Excluding individuals with a CRP level >10 mg/L consistently attenuated the significant associations across all markers of inflammation.Conclusion
These novel findings from a high risk population recruited through primary care suggest that sedentary behaviour may influence markers associated with inflammation, independent of MVPA, glycaemia and adiposity. 相似文献64.
65.
66.
Melanie P. Meijer zu Schlochtern Christian Rixen Sonja Wipf Johannes H. C. Cornelissen 《Ecological Research》2014,29(4):583-592
Owing to the increasing popularity of skiing and the upslope movement of the snow reliability line in mountain regions, more and more alpine environments are being turned into skiing areas, with strong impacts on ecosystem functions and biodiversity. Creation and management of ski slopes cause physical disturbance to soil and vegetation, while (artificial) snow supplements affect soil structure, chemistry, moisture and temperature regimes as well as shifts in snow season and growing season length. Vegetation–soil feedbacks may influence the outcome of these interactive effects on soil and vegetation, with possible consequences for soil erosion. Moreover, climate warming will lead to changing snow cover and duration, which will interact with ski slope management effects on soil and vegetation and its feedbacks. Based on a conceptual framework we review the main elements of these interactive effects on soil and vegetation on new and established ski slopes. We also set a research agenda with specific studies that could further advance our understanding of interacting ski slope management, winter climate, vegetation–soil feedbacks and ecosystem functioning. In such new investigations, alpine climate change ecology can probably learn much from the “experimental” disturbance and snow manipulations on ski slopes and vice versa. 相似文献
67.
The partitioning of limited resources commonly explains how different species can coexist within the same ecological community. In this 2010 study, the diets of three coexisting freshwater fishes (Cape galaxias Galaxias zebratus, n = 27; Cape kurper Sandelia capensis, n = 60; Breede River redfin Pseudobarbus burchelli, n = 77) were characterised and compared in three headwater streams in South Africa's Cape Fold Ecoregion using gut contents and stable isotope analyses. These data were analysed to ascertain whether the three species exploit distinct trophic niches. Both approaches provided evidence that these species occupy different trophic niches, though with some overlap. However, dietary differences among sites were not consistent and were probably influenced by site-specific factors like resource availability. Pseudobarbus burchelli had a broader niche breadth at Tierkloof Stream than the other two species, but not at Waaihoek or Tierstel Streams. Our results also suggest that P. burchelli consumed a more omnivorous diet than do the other two species, whereas S. capensis occupied a higher trophic position than the other two species and consumed vertebrates. Our findings suggest that these species occupy non-equivalent feeding niches in Cape Fold Ecoregion headwater streams, and that diet partitioning might facilitate their coexistence in these systems. 相似文献
68.
69.
Douglas E Bassett Jr Munira A Basrai Carla Connelly Katherine M Hyland Katsumi Kitagawa Melanie L Mayer Dwight M Morrow Andrew M Page Vicente A Resto Robert V Skibbens Philip Hieter 《Current opinion in genetics & development》1996,6(6):763-766
The completion of the genome sequence of the budding yeast Saccharomyces cerevisiae marks the dawn of an exciting new era in eukaryotic biology that will bring with it a new understanding of yeast, other model organisms, and human beings. This body of sequence data benefits yeast researchers by obviating the need for piecemeal sequencing of genes, and allows researchers working with other organisms to tap into experimental advantages inherent in the yeast system and learn from functionally characterized yeast gene products which are their proteins of interest. In addition, the yeast post-genome sequence era is serving as a testing ground for powerful new technologies, and proven experimental approaches are being applied for the first time in a comprehensive fashion on a complete eukaryotic gene repertoire. 相似文献
70.
Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented ‘cued’ and ‘non-cued’ conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18–25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation). 相似文献