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排序方式: 共有350条查询结果,搜索用时 15 毫秒
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Tomlinson IP Carvajal-Carmona LG Dobbins SE Tenesa A Jones AM Howarth K Palles C Broderick P Jaeger EE Farrington S Lewis A Prendergast JG Pittman AM Theodoratou E Olver B Walker M Penegar S Barclay E Whiffin N Martin L Ballereau S Lloyd A Gorman M Lubbe S;COGENT Consortium;CORGI Collaborators;EPICOLON Consortium Howie B Marchini J Ruiz-Ponte C Fernandez-Rozadilla C Castells A Carracedo A Castellvi-Bel S Duggan D Conti D Cazier JB Campbell H Sieber O Lipton L Gibbs P Martin NG Montgomery GW 《PLoS genetics》2011,7(6):e1002105
Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases. 相似文献
34.
Robert W. Howarth 《中国科学C辑(英文版)》2005,48(Z2)
Two-thirds of the coastal rivers and bays in the United States are degraded from nutrient pollution, and nitrogen inputs these waters continue to increase. The nitrogen comes from a variety of sources, including runoff from agricultural fields, concentrated animal feeding operations, atmospheric deposition from fossil fuel combustion, and sewage and septic wastes.Technical solutions for nitrogen pollution exist at reasonable cost. That most of these solutions have not yet been implemented to any significant extent across the United States suggests that new policy approaches are necessary. The best solution may involve a combination of voluntary and mandatory approaches, applying different approaches to different sources of nitrogen poilution. A watershed-based approach that relies heavily on voluntary mechanisms (such as crop-yield insurance to reduce over-fertilization) is likely to be the most effective for some sources of nitrogen (such as runoff from agricultural fields), while a uniform national regulatory approach may be better for others (such as NOx emissions from fossil fuel combustion). Implementation of management strategies should be carefully coupled to monitoring programs to assess the effectiveness of these strategies. While both nitrogen and phosphorus are important to control, the focus should be on nitrogen management, in part because nitrogen is more generally the causal agent of coastal eutrophication. Also, while nitrogen-control practices tend to also reduce phosphorus pollution, phosphorus-control practices often have little effect on nitrogen.Although current scientific and technical knowledge is sufficient to begin to make substantial progress toward solving coastal nitrogen pollution, progress will be made more quickly and more cost effectively with increased investment in appropriate scientific research. 相似文献
35.
Howarth FC Adem A Adeghate EA Al Ali NA Al Bastaki AM Sorour FR Hammoudi RO Ghaleb NA Chandler NJ Dobrzynski H 《Peptides》2005,26(4):691-700
The distribution of atrial natriuretic peptide (ANP) in blood plasma and cardiac muscle and its effects on ventricular myocyte contraction and intracellular free calcium concentration [Ca2+]i in the streptozotocin (STZ)-induced diabetic rat have been investigated. Blood plasma concentration and heart atrial and ventricular contents of ANP were significantly increased in STZ-treated rats compared to age-matched controls. STZ treatment increased the number of ventricular myocytes immunolabeled with antibodies against ANP. In control myocytes the percentage of cells that labeled positively and negatively were 17% versus 83%, respectively. However, in myocytes from STZ-treated rat the percentages were 52% versus 53%. Time to peak (TPK) shortening was significantly and characteristically prolonged in myocytes from STZ-treated rats (360+/-5 ms) compared to controls (305+/-5 ms). Amplitude of the Ca2+ transient was significantly increased in myocytes from STZ-treated rats compared to controls (0.39+/-0.02 versus 0.29+/-0.02 fura-2 RU in controls) and treatment with ANP reduced the amplitude of the Ca2+ transient to control levels. ANP may have a protective role in STZ-induced diabetic rat heart. 相似文献
36.
Pádár P Forgó P Kele Z Howarth NM Kovács L 《Nucleosides, nucleotides & nucleic acids》2005,24(5-7):743-745
The diastereoselective intramolecular 1,3-dipolar cycloaddition reaction of unsaturated nitrones, derived from methyl alpha-D-glucopyranoside with 2-furaldehyde and 2-(benzyloxy)acetaldehyde has been studied In our pevious studies with 2-furaldehyde, the cycloaddition resulted 3 diastereoisomers in a 3:1:1 ratio. In this article, how the number of the possible isomers generated by 1,3-cycloaddition could be reduced from 4 to 1 when 2-(benzyloxy)acetaldehyde was employed as an aldehyde is shown. 相似文献
37.
Terry T.‐K. Huang Susan B. Roberts Nancy C. Howarth Megan A. McCrory 《Obesity (Silver Spring, Md.)》2005,13(7):1205-1217
Objective: We present an updated method for identifying physiologically implausible dietary reports by comparing reported energy intake (rEI) with predicted energy requirements (pER), and we examine the impact of excluding these reports. Research Methods and Procedures: Adult data from the Continuing Survey of Food Intakes by Individuals 1994 to 1996 were used. pER was calculated from the dietary reference intake equations. Within‐subject variations and errors in rEI [coefficient of variation (CV) ~ 23%] over 2 days (d), pER (CV ~ 11%), and measured total energy expenditure (mTEE; doubly labeled water, CV ~ 8.2%) were propagated, where ±1 SD = . Thus, a report was identified as implausible if rEI was not within 78% to 122% of pER. Multiple cut‐offs between ±1 and ±2 SD were tested. Results: %rEI/pER = 81% in the total sample (n = 6499) and progressively increased to 95% in the ±1 SD sample (n = 2685). The ±1 to 1.4 SD samples yielded rEI‐weight associations closest to the theoretical relationship (mTEE to weight). Weak or spurious diet—BMI associations were present in the total sample; ±1 to 1.4 SD samples showed the strongest set of associations and provided the maximum n while maintaining biological plausibility. Discussion: Our methodology can be applied to different data sets to evaluate the impact of implausible rEIs on health outcomes. Implausible rEIs reduce the overall validity of a sample, and not excluding them may lead to inappropriate conclusions about potential dietary causes of health outcomes such as obesity. 相似文献
38.
Howarth B Edmunds M Gilbert F 《Evolution; international journal of organic evolution》2004,58(2):367-375
We tested the prediction that, if hoverflies are Batesian mimics, this may extend to behavioral mimicry such that their numerical abundance at each hour of the day (the daily activity pattern) is related to the numbers of their hymenopteran models. After accounting for site, season, microclimatic responses, and general hoverfly abundance at three sites in northwestern England, the residual numbers of mimics were significantly correlated positively with their models nine times of 17. Sixteen of 17 relationships were positive, itself a highly significant nonrandom pattern. Several eristaline flies showed significant relationships with honeybees even though some of them mimic wasps or bumblebees, perhaps reflecting an ancestral resemblance to honeybees. There was no evidence that good and poor mimics differed in their daily activity pattern relationships with models. However, the common mimics showed significant activity pattern relationships with their models, whereas the rarer mimics did not. We conclude that many hoverflies show behavioral mimicry of their hymenopteran models. 相似文献
39.
Two distinct regions of the large serine recombinase TnpX are required for DNA binding and biological function 总被引:1,自引:0,他引:1
Adams V Lucet IS Tynan FE Chiarezza M Howarth PM Kim J Rossjohn J Lyras D Rood JI 《Molecular microbiology》2006,60(3):591-601
The large serine recombinase, TnpX, from the Clostridium perfringens integrative mobilizable element Tn 4451 , consists of three domains and has two known DNA binding regions. In this study random and site-directed mutagenesis was used to identify other regions of TnpX that were required for biological activity. Genetic and biochemical analysis of these mutants led to the identification of important TnpX residues in the N-terminal catalytic pocket. In addition, another region of TnpX (aa 243–261), which is conserved within large serine recombinases, was shown to be essential for both excision and insertion. Mutation of charged residues within this region led to a loss of biological activity and aberrant DNA binding. This phenotype was mediated by interaction with the distal DNA binding region (aa 598–707). In these mutants, removal of residues 598–707 resulted in loss of DNA binding, despite the presence of the primary DNA binding region (aa 533–583). Analysis of mutations within the aa 243–261 region indicated that different protein conformations were involved in the insertion and the excision reactions. In summary, we have shown that TnpX is a complex protein that has multiple intra- and intermolecular interaction sites, providing insight into the structural and functional complexity of this important enzyme family. 相似文献
40.
Reconciling Carbon-cycle Concepts, Terminology, and Methods 总被引:5,自引:1,他引:4
F. S. Chapin III G. M. Woodwell J. T. Randerson E. B. Rastetter G. M. Lovett D. D. Baldocchi D. A. Clark M. E. Harmon D. S. Schimel R. Valentini C. Wirth J. D. Aber J. J. Cole M. L. Goulden J. W. Harden M. Heimann R. W. Howarth P. A. Matson A. D. McGuire J. M. Melillo H. A. Mooney J. C. Neff R. A. Houghton M. L. Pace M. G. Ryan S. W. Running O. E. Sala W. H. Schlesinger E.-D. Schulze 《Ecosystems》2006,9(7):1041-1050
Recent projections of climatic change have focused a great deal of scientific and public attention on patterns of carbon (C)
cycling as well as its controls, particularly the factors that determine whether an ecosystem is a net source or sink of atmospheric
carbon dioxide (CO2). Net ecosystem production (NEP), a central concept in C-cycling research, has been used by scientists to represent two different
concepts. We propose that NEP be restricted to just one of its two original definitions—the imbalance between gross primary
production (GPP) and ecosystem respiration (ER). We further propose that a new term—net ecosystem carbon balance (NECB)—be
applied to the net rate of C accumulation in (or loss from [negative sign]) ecosystems. Net ecosystem carbon balance differs
from NEP when C fluxes other than C fixation and respiration occur, or when inorganic C enters or leaves in dissolved form.
These fluxes include the leaching loss or lateral transfer of C from the ecosystem; the emission of volatile organic C, methane,
and carbon monoxide; and the release of soot and CO2 from fire. Carbon fluxes in addition to NEP are particularly important determinants of NECB over long time scales. However,
even over short time scales, they are important in ecosystems such as streams, estuaries, wetlands, and cities. Recent technological
advances have led to a diversity of approaches to the measurement of C fluxes at different temporal and spatial scales. These
approaches frequently capture different components of NEP or NECB and can therefore be compared across scales only by carefully
specifying the fluxes included in the measurements. By explicitly identifying the fluxes that comprise NECB and other components
of the C cycle, such as net ecosystem exchange (NEE) and net biome production (NBP), we can provide a less ambiguous framework
for understanding and communicating recent changes in the global C cycle. 相似文献