Inactivation of Dicer1 in Steroidogenic factor 1-positive cells reveals tissue-specific requirement for Dicer1 in adrenal, testis, and ovary

<p>Abstract</p> <p>Background</p> <p>The synthesis of microRNA (miRNA) is a multi-step process that requires the action of the ribonuclease Dicer1. Dicer1 is responsible for the final processing of miRNA and has been implicated in cellular processes such as proliferation, apoptosis, and differentiation. Mouse embryos lacking <it>Dicer1 </it>die in early embryogenesis. In this study, we investigated whether <it>Dicer1 </it>is required for development of adrenal, testis, and ovary in mouse embryos.</p> <p>Results</p> <p>To target <it>Dicer1 </it>deletion specifically in developing adrenals and gonads, we used Steroidogenic factor 1-cre (<it>Sf1/Cre</it>) line in which Cre recombinase is active in the progenitor cells of adrenals and gonads. Lack of <it>Dicer1 </it>in the SF1-positive cells did not affect formation and early differentiation of the adrenals and gonads. However, increasing numbers of apoptotic cells were first detected in the <it>Dicer1 </it>knockout adrenal cortex at 18.5 days post coitum (dpc), followed by apoptosis of somatic cells and germ cells in the testis at postnatal day 0. Affected adrenal and testes underwent complete degeneration 48 hrs after the onset of apoptosis. However, ovaries were not affected at least until postnatal day 5, when the animals died due to adrenal insufficiency.</p> <p>Conclusions</p> <p><it>Dicer1 </it>is dispensable for formation and differentiation of fetal tissues derived from the SF1-positive adrenogonadal primordium. <it>Dicer1 </it>is essential for maintaining cell survival in adrenal and testis; however, development of the ovary from fetal stages to postnatal day 5 does not require the presence of <it>Dicer1</it>. Our results reveal a tissue-specific requirement of <it>Dicer1 </it>and microRNAs. Future research is needed to understand how the tissue-specific role of <it>Dicer1 </it>is established.</p

Funding Source and Research Report Quality in Nutrition Practice-Related Research

BACKGROUND: The source of funding is one of many possible causes of bias in scientific research. One method of detecting potential for bias is to evaluate the quality of research reports. Research exploring the relationship between funding source and nutrition-related research report quality is limited and in other disciplines the findings are mixed. OBJECTIVE: The purpose of this study is to determine whether types of funding sources of nutrition research are associated with differences in research report quality. DESIGN: A retrospective study of research reporting quality, research design and funding source was conducted on 2539 peer reviewed research articles from the American Dietetic Association's Evidence Analysis Library® database. RESULTS: Quality rating frequency distributions indicate 43.3% of research reports were rated as positive, 50.1% neutral, and 6.6% as negative. Multinomial logistic regression results showed that while both funding source and type of research design are significant predictors of quality ratings (χ2 = 118.99, p≤0.001), the model's usefulness in predicting overall research report quality is little better than chance. Compared to research reports with government funding, those not acknowledging any funding sources, followed by studies with University/hospital funding were more likely to receive neutral vs positive quality ratings, OR = 1.85, P <0.001 and OR = 1.54, P<0.001, respectively and those that did not report funding were more likely to receive negative quality ratings (OR = 4.97, P<0.001). After controlling for research design, industry funded research reports were no more likely to receive a neutral or negative quality rating than those funded by government sources. CONCLUSION: Research report quality cannot be accurately predicted from the funding source after controlling for research design. Continued vigilance to evaluate the quality of all research regardless of the funding source and to further understand other factors that affect quality ratings are warranted

Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells

Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and non-functional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-κB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection