Factors related to adolescent drinking in Appalachia

Objectives: To examine the relationships among parental monitoring, perceptions of peer drinking, and adolescent alcohol consumption. Methods: Tenth- and 12thgrade students (N=648) in a rural, Appalachian county were surveyed. Results: A binomial logistic regression revealed a composite of those who had perceptions that many peers drank, low parental monitoring, and no biological male guardian in the home were 8.496 times more likely to have ever been drunk. Other characteristics resulted in lower odds. Conclusions: Parental monitoring and perceptions of peer drinking were important predictors of drinking in this rural sample. Prevention efforts in school and at home should address both variables

Why Are There So Few Female Leaders in Higher Education: A Case of Structure or Agency?

A significant gender imbalance remains at executive management level within higher education despite a number of initiatives to increase the number of women in the leadership pipeline and ensure they are better prepared for these roles. This article presents findings from a recent study on the appointment of deputy and pro vice chancellors in pre-1992 English universities that provide fresh insights into why this might be the case. These findings challenge the notion of women’s missing agency - characterised by a lack of confidence or ambition and a tendency to opt out of applying for the top jobs - as an explanation for their continued under-representation. Rather, they highlight the importance of three structural factors associated with the selection process: mobility and external career capital, conservatism, and homosociability. An approach of ‘fixing’ the women is therefore unlikely to be sufficient in redressing the current gender imbalance within university executive management teams

Liquid Sucrose Consumption Promotes Obesity and Impairs Glucose Tolerance Without Altering Circulating Insulin Levels

© 2018 The Obesity Society Objective: Multiple factors contribute to the rising rates of obesity and to difficulties in weight reduction that exist in the worldwide population. Caloric intake via sugar-sweetened beverages may be influential. This study tested the hypothesis that liquid sucrose intake promotes obesity by increasing serum insulin levels and tissue lipid accumulation. Methods: C57BL/6J mice were given 30% sucrose in liquid form. Changes in weight gain, body composition, energy expenditure (EE), and tissue lipid content were measured. Results: Mice drinking sucrose gained more total body mass (TBM), had greater fat mass, and displayed impaired glucose tolerance relative to control mice. These metabolic changes occurred without alterations in circulating insulin levels and despite increases in whole body EE. Lipid accrued in liver, but not skeletal muscle, of sucrose-consuming mice. Oxygen consumption (VO2) correlated with fat-free mass and moderately with TBM, but not with fat mass. ANCOVA for treatment effects on EE, with TBM, VO2, lean body mass, and fat-free mass taken as potential covariates for EE, revealed VO2 as the most significant correlation. Conclusions: Weight gain induced by intake of liquid sucrose in mice is associated with lipid accrual in liver, but not skeletal muscle, and occurs without an increase in circulating insulin

The interface between silicon and a high-k oxide

The ability to follow Moore's Law has been the basis of the tremendous success of the semiconductor industry in the past decades. To date, the greatest challenge for device scaling is the required replacement of silicon dioxide-based gate oxides by high-k oxides in transistors. Around 2010 high-k oxides are required to have an atomically defined interface with silicon without any interfacial SiO2 layer. The first clean interface between silicon and a high-K oxide has been demonstrated by McKee et al. Nevertheless, the interfacial structure is still under debate. Here we report on first-principles calculations of the formation of the interface between silicon and SrTiO3 and its atomic structure. Based on insights into how the chemical environment affects the interface, a way to engineer seemingly intangible electrical properties to meet technological requirements is outlined. The interface structure and its chemistry provide guidance for the selection process of other high-k gate oxides and for controlling their growth. Our study also shows that atomic control of the interfacial structure can dramatically improve the electronic properties of the interface. The interface presented here serves as a model for a variety of other interfaces between high-k oxides and silicon.Comment: 10 pages, 2 figures (one color

Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice

© 2017 American Society for Investigative Pathology Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (\u3e250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+ cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease

Db / db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet

© 2017 Susan J. Burke et al. To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass

Low-Intensity Exercise Induces Acute Shifts In Liver And Skeletal Muscle Substrate Metabolism But Not Chronic Adaptations In Tissue Oxidative Capacity

Adaptations in hepatic and skeletal muscle substrate metabolism following acute and chronic (6 wk; 5 days/wk; 1 h/day) low-intensity treadmill exercise were tested in healthy male C57BL/6J mice. Low-intensity exercise maximizes lipid utilization; therefore, we hypothesized pathways involved in lipid metabolism would be most robustly affected. Acute exercise nearly depleted liver glycogen immediately postexercise (0 h), whereas hepatic triglyceride (TAG) stores increased in the early stages after exercise (0-3 h). Also, hepatic peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) gene expression and fat oxidation (mitochondrial and peroxisomal) increased immediately postexercise (0 h), whereas carbohydrate and amino acid oxidation in liver peaked 24-48 h later. Alternatively, skeletal muscle exhibited a less robust response to acute exercise as stored substrates (glycogen and TAG) remained unchanged, induction of PGC-1 alpha gene expression was delayed (up at 3 h), and mitochondrial substrate oxidation pathways (carbohydrate, amino acid, and lipid) were largely unaltered. Peroxisomal lipid oxidation exhibited the most dynamic changes in skeletal muscle substrate metabolism after acute exercise; however, this response was also delayed (peaked 3-24 h postexercise), and expression of peroxisomal genes remained unaffected. Interestingly, 6 wk of training at a similar intensity limited weight gain, increased muscle glycogen, and reduced TAG accrual in liver and muscle; however, substrate oxidation pathways remained unaltered in both tissues. Collectively, these results suggest changes in substrate metabolism induced by an acute low-intensity exercise bout in healthy mice are more rapid and robust in liver than in skeletal muscle; however, training at a similar intensity for 6 wk is insufficient to induce remodeling of substrate metabolism pathways in either tissue. NEW & NOTEWORTHY Effects of low-intensity exercise on substrate metabolism pathways were tested in liver and skeletal muscle of healthy mice. This is the first study to describe exercise-induced adaptations in peroxisomal lipid metabolism and also reports comprehensive adaptations in mitochondrial substrate metabolism pathways (carbohydrate, lipid, and amino acid). Acute low-intensity exercise induced shifts in mitochondrial and peroxisomal metabolism in both tissues, but training at this intensity did not induce adaptive remodeling of metabolic pathways in healthy mice

Structural insights into RNA processing by the human RISC-loading complex.

Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2

Response of liver metabolic pathways to ketogenic diet and exercise are not additive

© Lippincott Williams & Wilkins. Purpose Studies suggest ketogenic diets (KD) produce favorable outcomes (health and exercise performance); however, most rodent studies have used a low-protein KD, which does not reflect the normal- to high-protein KD used by humans. Liver has an important role in ketoadaptation due to its involvement in gluconeogenesis and ketogenesis. This study was designed to test the hypothesis that exercise training (ExTr) while consuming a normal-protein KD (NPKD) would induce additive/synergistic responses in liver metabolic pathways. Methods Lean, healthy male C57BL/6J mice were fed a low-fat control diet (15.9% kcal protein, 11.9% kcal fat, 72.2% kcal carbohydrate) or carbohydrate-deficient NPKD (16.1% protein, 83.9% kcal fat) for 6 wk. After 3 wk on the diet, half were subjected to 3-wk treadmill ExTr (5 d·wk-1, 60 min·d-1, moderate-vigorous intensity). Upon conclusion, metabolic and endocrine outcomes related to substrate metabolism were tested in liver and pancreas. Results NPKD-fed mice had higher circulating β-hydroxybutyrate and maintained glucose at rest and during exercise. Liver of NPKD-fed mice had lower pyruvate utilization and greater ketogenic potential as evidenced by higher oxidative rates to catabolize lipids (mitochondrial and peroxisomal) and ketogenic amino acids (leucine). ExTr had higher expression of the gluconeogenic gene, Pck1, but lower hepatic glycogen, pyruvate oxidation, incomplete fat oxidation, and total pancreas area. Interaction effects between the NPKD and ExTr were observed for intrahepatic triglycerides, as well as genes involved in gluconeogenesis, ketogenesis, mitochondrial fat oxidation, and peroxisomal markers; however, none were additive/synergistic. Rather, in each instance the interaction effects showed the NPKD and ExTr opposed each other. Conclusions An NPKD and an ExTr independently induce shifts in hepatic metabolic pathways, but changes do not seem to be additive/synergistic in healthy mice