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41.
KASSO DAÏNOU JEAN‐PHILIPPE BIZOUX JEAN‐LOUIS DOUCET GRÉGORY MAHY OLIVIER J. HARDY MYRIAM HEUERTZ 《Molecular ecology》2010,19(20):4462-4477
The impact of the Pleistocene climate oscillations on the structure of biodiversity in tropical regions remains poorly understood. In this study, the forest refuge theory is examined at the molecular level in Milicia excelsa, a dioecious tree with a continuous range throughout tropical Africa. Eight nuclear microsatellites (nSSRs) and two sequences and one microsatellite from chloroplast DNA (cpDNA) showed a deep divide between samples from Benin and those from Lower Guinea. This suggests that these populations were isolated in separate geographical regions, probably for several glacial cycles of the Pleistocene, and that the nuclear gene pools were not homogenized despite M. excelsa’s wind‐pollination syndrome. The divide could also be related to seed dispersal patterns, which should be largely determined by the migration behaviour of M. excelsa’s main seed disperser, the frugivorous bat Eidolon helvum. Within Lower Guinea, a north–south divide, observed with both marker types despite weak genetic structure (nSSRs: FST = 0.035, cpDNA: GST = 0.506), suggested the existence of separate Pleistocene refugia in Cameroon and the Gabon/Congo region. We inferred a pollen‐to‐seed dispersal distance ratio of c. 1.8, consistent with wide‐ranging gene dispersal by both wind and bats. Simulations in an Approximate Bayesian Computation framework suggested low nSSR and cpDNA mutation rates, but imprecise estimates of other demographic parameters, probably due to a substantial gene flow between the Lower Guinean gene pools. The decline of genetic diversity detected in some Gabonese populations could be a consequence of the relatively recent establishment of a closed canopy forest, which could negatively affect M. excelsa’s reproductive system. 相似文献
42.
Jérémie Roux Michel Carles Hidefumi Koh Arnaud Goolaerts Michael T. Ganter Brian B. Chesebro Marybeth Howard Benjamin T. Houseman Walter Finkbeiner Kevan M. Shokat Agnès C. Paquet Michael A. Matthay Jean-Fran?ois Pittet 《The Journal of biological chemistry》2010,285(7):4278-4290
Exogenous or endogenous β2-adrenergic receptor agonists enhance alveolar epithelial fluid transport via a cAMP-dependent mechanism that protects the lungs from alveolar flooding in acute lung injury. However, impaired alveolar fluid clearance is present in most of the patients with acute lung injury and is associated with increased mortality, although the mechanisms responsible for this inhibition of the alveolar epithelial fluid transport are not completely understood. Here, we found that transforming growth factor β1 (TGF-β1), a critical mediator of acute lung injury, inhibits β2-adrenergic receptor agonist-stimulated vectorial fluid and Cl− transport across primary rat and human alveolar epithelial type II cell monolayers. This inhibition is due to a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis mediated by a phosphatidylinositol 3-kinase (PI3K)-dependent heterologous desensitization and down-regulation of the β2-adrenergic receptors. Consistent with these in vitro results, inhibition of the PI3K pathway or pretreatment with soluble chimeric TGF-β type II receptor restored β2-adrenergic receptor agonist-stimulated alveolar epithelial fluid transport in an in vivo model of acute lung injury induced by hemorrhagic shock in rats. The results demonstrate a novel role for TGF-β1 in impairing the β- adrenergic agonist-stimulated alveolar fluid clearance in acute lung injury, an effect that could be corrected by using PI3K inhibitors that are safe to use in humans. 相似文献
43.
Brock C. Christensen Karl T. Kelsey Shichun Zheng E. Andres Houseman Carmen J. Marsit Margaret R. Wrensch Joseph L. Wiemels Heather H. Nelson Margaret R. Karagas Lawrence H. Kushi Marilyn L. Kwan John K. Wiencke 《PLoS genetics》2010,6(7)
Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage I–IV) women from the Kaiser Division of Research Pathways Study and the Illumina GoldenGate methylation bead-array platform, we measured 1,413 autosomal CpG loci associated with 773 cancer-related genes and validated select CpG loci with Sequenom EpiTYPER. Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly (Q-values <0.05) associated with altered methylation of 209, 74, 183, 69, and 130 loci, respectively. Unsupervised clustering, using a recursively partitioned mixture model (RPMM), of all autosomal CpG loci revealed eight distinct methylation classes. Methylation class membership was significantly associated with patient race (P<0.02) and tumor size (P<0.001) in univariate tests. Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly (P<0.0001) associated with methylation class membership. Breast cancer prognostic characteristics and risk-related exposures appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns. 相似文献
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45.
The development of peptide and protein microarrays has created enormous opportunities in biomedical research. Current chip-based assays are well suited for identifying candidate protein or enzyme activities but still require conventional solution phase experiments to validate hits. Here, three surface-engineering strategies for microarray design are described and are illustrated in the development of a peptide chip for the quantitative analysis of kinase activity on solid support. These strategies promise to widen the application of microarrays by permitting the evaluation of hits in a chip-based format. 相似文献
46.
47.
Richard Idro Godfrey Otieno Steven White Anderson Kahindi Greg Fegan Bernhards Ogutu Sadik Mithwani Kathryn Maitland Brian GR Neville Charles RJC Newton 《Malaria journal》2005,4(1):1-10
Background
Intermittent preventive treatment of malaria during pregnancy (IPTp) is a key intervention in the national strategy for malaria control in Tanzania. SP, the current drug of choice, is recommended to be administered in the second and third trimesters of pregnancy during antenatal care (ANC) visits. To allow for a proper design of planned scaling up of IPT services in Tanzania it is useful to understand the IPTp strategy's acceptability to health managers, ANC service providers and pregnant women. This study assesses the knowledge, attitudes and practices of these groups in relation to malaria control with emphasis on IPTp services.Methods
The study was conducted in February 2004, in Korogwe District, Tanzania. It involved in-depth interviews with the district medical officer (DMO), district hospital medical officer in charge and relevant health service staff at two peripheral dispensaries, and separate focus group discussions (FGDs) with district Council Health Management Team members at district level and pregnant women at dispensary and community levels.Results
Knowledge of malaria risks during pregnancy was high among pregnant women although some women did not associate coma and convulsions with malaria. Contacting traditional healers and self-medication with local herbs for malaria management was reported to be common. Pregnant women and ANC staff were generally aware of SP as the drug recommended for IPTp, albeit some nurses and the majority of pregnant women expressed concern about the use of SP during pregnancy. Some pregnant women testified that sometimes ANC staff allow the women to swallow SP tablets at home which gives a room for some women to throw away SP tablets after leaving the clinic. The DMO was sceptical about health workers' compliance with the direct observed therapy in administering SP for IPTp due to a shortage of clean water and cups at ANC clinics. Intensified sensitization of pregnant women about the benefits of IPTp was suggested by the study participants as an important approach for improving IPTp compliance.Conclusion
The successful implementation of the IPTp strategy in Tanzania depends on the proper planning of, and support to, the training of health staff and sustained sensitization of pregnant women at health facility and community levels about the benefits of IPTp for the women and their unborn babies. 相似文献48.
D Ribuffo M Marcellino G R Barnett N D Houseman N Scuderi 《Plastic and reconstructive surgery》2001,108(6):1604-1608
After the reported safe transverse rectus abdominis myocutaneous (TRAM) flap after liposuction of the abdomen, two cases of bipedicled reconstruction with this flap after abdominoplasty were successfully performed. This operation has not previously been considered possible because of the transection of the perforator arteries during the undermining of the abdomen. To examine the possible reperfusion of the perforator arteries, the authors studied the perforator arteries of 10 patients before they underwent abdominoplasty and at 1 week, 3 months, and 6 months after the operation. The arteries were studied with color-duplex scanning and power Doppler, using 10-MHz superficial probes, and their position was marked on a map. A cadaver study of a woman who had had an abdominoplasty 10 years before her death is also presented. In every patient, reperfusion of all perforator arteries was documented, starting from the control at 1 month. In no case was the caliber of the reperfused vessels more than 40 percent of the original diameter (maximum: 0.53 mm). This was also confirmed by the cadaver study. In conclusion, after an abdominoplasty operation, constant reperfusion of the perforator arteries of the rectus muscles occurs. However, the diameter of the arteries may not be enough to provide the necessary blood supply for a TRAM flap, which is therefore strongly discouraged by the authors after abdominoplasty in favor of a vertical rectus abdominis muscle (VRAM) flap. A liposuction, which does not necessarily disrupt the perforators, is not an absolute contraindication for a TRAM flap, provided that an accurate color-duplex scanning study is done. 相似文献
49.
Ashley A Smith Yen-Tsung Huang Melissa Eliot E Andres Houseman Carmen J Marsit John K Wiencke Karl T Kelsey 《Epigenetics》2014,9(6):873-883
Glioblastoma multiforme (GBM) is the most aggressive of all brain tumors, with a median survival of less than 1.5 years. Recently, epigenetic alterations were found to play key roles in both glioma genesis and clinical outcome, demonstrating the need to integrate genetic and epigenetic data in predictive models. To enhance current models through discovery of novel predictive biomarkers, we employed a genome-wide, agnostic strategy to specifically capture both methylation-directed changes in gene expression and alternative associations of DNA methylation with disease survival in glioma. Human GBM-associated DNA methylation, gene expression, IDH1 mutation status, and survival data were obtained from The Cancer Genome Atlas. DNA methylation loci and expression probes were paired by gene, and their subsequent association with survival was determined by applying an accelerated failure time model to previously published alternative and expression-based association equations. Significant associations were seen in 27 unique methylation/expression pairs with expression-based, alternative, and combinatorial associations observed (10, 13, and 4 pairs, respectively). The majority of the predictive DNA methylation loci were located within CpG islands, and all but three of the locus pairs were negatively correlated with survival. This finding suggests that for most loci, methylation/expression pairs are inversely related, consistent with methylation-associated gene regulatory action. Our results indicate that changes in DNA methylation are associated with altered survival outcome through both coordinated changes in gene expression and alternative mechanisms. Furthermore, our approach offers an alternative method of biomarker discovery using a priori gene pairing and precise targeting to identify novel sites for locus-specific therapeutic intervention. 相似文献