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Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisticated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance. 相似文献
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Bendamustine and rituximab in combination with lenalidomide in patients with chronic lymphocytic leukemia 下载免费PDF全文
Jasmin Bahlo Sandra Kluth Christina Rhein Paula Cramer Carolin Gross‐Ophoff Petra Langerbeins Anna‐Maria Fink Barbara Eichhorst Karl‐Anton Kreuzer Norbert Fischer Eugen Tausch Stephan Stilgenbauer Sebastian Böttcher Hartmut Döhner Michael Kneba Martin Dreyling Mascha Binder Michael Hallek Clemens‐Martin Wendtner the German CLL Study Group 《European journal of haematology》2016,97(3):253-260
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Suzanne R. Soliman Martin MacDowell Allison E. Schriever Michael Glasser Marieke D. Schoen 《American journal of pharmaceutical education》2012,76(10)
Objectives. To develop, implement, and assess an interprofessional rural health professions program for pharmacy and medical students.Design. A recruitment and admissions process was developed that targeted students likely to practice in rural areas. Pharmacy students participated alongside medical students in completing the Rural Health Professions program curriculum, which included monthly lecture sessions and assignments, and a capstone clinical requirement in the final year.Assessment. Fourteen pharmacy students and 33 medical students were accepted into the program during the first 2 years of the Rural Health Professions program. Approximately 90% of the rural health professions students were originally from rural areas.Conclusions. The rural health professions program is an interprofessional approach to preparing healthcare providers to practice in rural communities. 相似文献
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Badrick E Bobak M Britton A Kirschbaum C Marmot M Kumari M 《The Journal of clinical endocrinology and metabolism》2008,93(3):750-757
CONTEXT: Evidence for an association between alcohol consumption and activity of the hypothalamic-pituitary-adrenal (HPA) axis is inconclusive. OBJECTIVE: Our objective was to assess the relationship between indices of alcohol consumption and salivary cortisol concentration. DESIGN: This was a cross-sectional study of alcohol consumption and cortisol secretion from phase 7 (2002-2004) of the Whitehall II study. SETTING: An occupational cohort originally recruited in 1985-1987 was included in the study. PARTICIPANTS: A total of 2693 men and 977 women had information on cortisol levels and alcohol consumption. OUTCOME MEASURES: Saliva samples were taken on waking, waking+0.5, 2.5, 8, and 12 h, and bedtime for the assessment of cortisol. RESULTS: In men there was a positive association between cortisol and units of alcohol intake per week (3% increase in cortisol per unit of alcohol consumed; P=0.010). The slope of cortisol decline over the day in heavy drinkers was reduced (heavy drinkers beta=-0.155, moderate drinkers beta=-0.151), indicating reduced control of the HPA axis in heavy drinkers. In women the cortisol awakening response was greater in heavy drinkers 14.15 nmol/liter (9.12-19.17) compared with moderate drinkers 8.69 nmol/liter (7.72-9.67) (P=0.037). CONCLUSIONS: This study suggests that alcohol consumption is associated with activation of the HPA axis. These results are not due to alcohol consumption on the day, suggesting chronic changes of the HPA axis in heavy drinking groups. 相似文献
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Previous studies using the Hep G2-based VA cells showed that ethanol metabolism resulted in both cytotoxicity and impaired DNA synthesis, causing reduced accumulation of cells in culture. To further characterize the ethanol oxidation-mediated impairment of DNA synthesis we analyzed the cell-cycle progression of VA cells. These studies showed approximately a 6-fold increase in the percentage of cells in the G2/M phase of the cell cycle after 4 days of ethanol exposure. The G2/M transition requires activity of the cyclin-dependent kinase, Cdc2. Cdc2 is positively regulated by association with cyclin B1, and negatively regulated by phosphorylation of amino acids Thr14 and Tyr15. Immunoblot analysis revealed that ethanol metabolism had little affect on total Cdc2 content in these cells, but resulted in the accumulation of up to 20 times the amount of cyclin B1, indicating that cyclin B1 was available for formation of Cdc2/cyclin B1 complexes. Co-immunoprecipitation revealed that 6 times more Cdc2/cyclin B1 complexes were present in the ethanol-treated cells compared with the controls. Investigation of the phosphorylation state of Cdc2 revealed that ethanol oxidation increased the amount of the phosphorylated inactive form of Cdc2 by approximately 3-fold. Thus, the impairment in cell-cycle progression could not be explained by a lack of cyclin B1, or the ability of Cdc2 and cyclin B1 to associate, but instead resulted, at least in part, from impaired Cdc2 activity. In conclusion, ethanol oxidation by VA cells results in a G2/M cell-cycle arrest, mediated by accumulation of the phosphorylated inactive form of Cdc2. 相似文献