Conditional Expression of Smad7 in Pancreatic β Cells Disrupts TGF-β Signaling and Induces Reversible Diabetes Mellitus

Identification of signaling pathways that maintain and promote adult pancreatic islet functions will accelerate our understanding of organogenesis and improve strategies for treating diseases like diabetes mellitus. Previous work has implicated transforming growth factor-β (TGF-β) signaling as an important regulator of pancreatic islet development, but has not established whether this signaling pathway is required for essential islet functions in the adult pancreas. Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-β signaling, to identify distinct roles for this pathway in adult and embryonic β cells. Smad7 expression in Pdx1 (+) embryonic pancreas cells resulted in striking embryonic β cell hypoplasia and neonatal lethality. Conditional expression of Smad7 in adult Pdx1 (+) cells reduced detectable β cell expression of MafA, menin, and other factors that regulate β cell function. Reduced pancreatic insulin content and hypoinsulinemia produced overt diabetes that was fully reversed upon resumption of islet TGF-β signaling. Thus, our studies reveal that TGF-β signaling is crucial for establishing and maintaining defining features of mature pancreatic β cells

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe

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Not AvailablePurpose – This paper aims to optimize the quantum of aonla pulp that could be mixed with guava pulp to make a nutritional rich fruit bar. The developed fruit bar will not only help in the improvement of processing value of both Guava and underused but highly nutritional Aonla but also serve the purpose of improvement in nutritional status of consumers. Design/methodology/approach – Response surface methodology (RSM) using Box–Behnken design was used with the process variables as aonla and guava pulp ratio, PR (30:70, 40:60, 50:50); pectin concentration, PC (0, 0.15, 0.30%); and drying temperature, DT (50, 60, 70°C) for optimization of process conditions. The prepared mixed fruit leather was evaluated for physico-chemical, textural and sensory properties such as titratable acidity (TA), ascorbic acid content (AA), L value (lightness), cutting force (CF), taste and overall acceptability (OAA). Findings – Second-order regression models fitted for TA, AA, L value (lightness), CF, taste and OAA were highly significant (P = 0.01) with the coefficient of determination (R2 = 0.85). The TA and AA of mixed fruit bar increased whereas L value, CF, taste and OAA decreased with increasing level of aonla pulp in the blend formulation. The optimum process conditions for mixed aonla-guava bar with desirable characteristics were 40:60 (PR), 0.02% (PC) and 56°C (DT). The corresponding optimum values of TA, AA, L value, CF, taste and OAA were 1.00%, 164 mg/100 g, 50, 5066 g, 7.83 and 7.92, respectively. The design formulation and data analysis using RSM validated the optimum solution. Originality/value – This paper demonstrates that optimum blending of aonla and guava pulp has improved the overall nutritional characteristics and acceptability of the final product. This will not only help in reducing the associated post-harvest losses but also encourage the cultivators/local processing industries by stabilizing the price during glut sea.Not Availabl

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Not AvailableThis paper aims to optimize the quantum of aonla pulp that could be mixed with guava pulp to make a nutritional rich fruit bar. The developed fruit bar will not only help in the improvement of processing value of both Guava and underused but highly nutritional Aonla but also serve the purpose of improvement in nutritional status of consumers.Not Availabl

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Not AvailableHighthrouput sequencing of small RNA of H5N1 infected and mock infected chicken lungs. 297 miRNAs identified in mock-infected and 201 miRNAs identified in AIV infected chicken lungs. 36 miRNAs were upregulated and 90 were downregulated during H5N1 infection. Functional analysis and gene ontology of predicted target genes of expressed miRNAs. MAPK pathway, NF-κB, IGF and gga-let-7b might play important role during H5N1 pathogenesis.Not Availabl