Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10^-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10^-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10[superscript -9]), BMI (5.4 x 10^-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.

Background: GoGirlGo! (GGG) is designed to increase girls’ physical activity (PA) using a health behavior and PA-based curriculum and is widely available for free to afterschool programs across the nation. However, GGG has not been formally evaluated. The purpose of this pilot study was to evaluate the effectiveness of the GGG curricula to improve PA, and self-efficacy for and enjoyment of PA in elementary aged girls (i.e., 5-13 years).

Methods: Nine afterschool programs were recruited to participate in the pilot (within subjects repeated measures design). GGG is a 12-week program, with a once a week, one-hour lesson with 30 minutes of education and 30 minutes of PA). Data collection occurred at baseline, mid (twice), post, and at follow-up (3-months after the intervention ended). PA was assessed via accelerometry at each time point. Self-efficacy for and enjoyment of PA was measured using the Self-Efficacy Scale and the Short-PA enjoyment scale and was assessed at baseline, post, and follow-up. Fidelity was assessed at midpoint.

Results: Across all age groups there was a statistically significant increase in PA. Overall, on days GGG was offered girls accumulated an average of 11 minutes of moderate-to-vigorous PA compared to 8 minutes during non-GGG days. There was a statistically significant difference in girls’ self-efficacy for PA reported between baseline and post, which was maintained at follow-up. An improvement in enjoyment of PA for girls was found between baseline and follow-up. According to fidelity assessment, 89% of the activities within the curriculum were completed each lesson. Girls appeared to respond well to the curriculum but girls 5-7 years had difficulties paying attention and understanding discussion questions.

Conclusions: Even though there were statistically significant differences in self-efficacy for PA and enjoyment of PA, minimal increases in girls’ PA were observed. GGG curricula improvements are warranted. Future GGG programming should explore offering GGG every day, modifying activities so that they are moderate-to-vigorous in intensity, and providing additional trainings that allow staff to better implement PA and improve behavior management techniques. With modifications, GGG could provide a promising no-cost curriculum that afterschool programs may implement to help girls achieve recommendations for PA.

Bioethics is an important aspect of the core competency of biology of understanding the relationship between science and society, but because of the controversial nature of the topics covered in bioethics courses, different groups of students may experience identity conflicts or discomfort when learning about them. However, no previous studies have investigated the impact of undergraduate bioethics students’ experiences in bioethics courses on their opinions and comfort. To fill this gap in knowledge, we investigated undergraduate bioethics students’ attitudes about and comfort when learning abortion, gene editing, and physician assisted suicide, as well as how their gender, religious, and political identity influence their attitudes and changes in their attitudes after instruction. We found that religious students were less supportive of gene editing, abortion, and physician assisted suicide than nonreligious students, non-liberal students were less supportive of abortion and physician assisted suicide than liberal students, and women were less supportive of abortion than men. Additionally, we found that religious students were less comfortable than nonreligious students when learning about gene editing, abortion, and physician assisted suicide, and non-liberal students were less comfortable than liberal students when learning about abortion. When asked how their comfort could have been improved, those who felt that their peers or instructors could have done something to increase their comfort most commonly cited that including additional unbiased materials or incorporating materials and discussions that cover both sides of every controversial issue would have helped them to feel more comfortable when learning about gene editing, abortion, and physician assisted suicide. Finally, we found that students who were less comfortable learning about abortion and physician assisted suicide were less likely to participate in discussions regarding those topics. Our findings show that students in different groups not only tend to have different support for controversial topics like gene editing, abortion, and physician assisted suicide, but they also feel differentially comfortable when learning about them, which in turn impacts their participation. We hope that this work helps instructors to recognize the importance of their students’ comfort to their learning in bioethics courses, and from this study, they can take away the knowledge that students feel their comfort could be most improved by the incorporation of additional inclusive materials and course discussions regarding the controversial topics covered in the course.

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m²) and lean (BMI, 22±1 kg/m²) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h^-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired β-F1-ATPase translation as an important consequence of obesity.