A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.

We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs, and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io.

Relationship between serum ß-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation that can progress to inflammation (nonalcoholic steatohepatitis, NASH), and fibrosis. Serum ß-hydroxybutyrate (ß-HB), a product of the ketogenic pathway, is commonly used as a surrogate marker for hepatic fatty acid oxidation (FAO). However, it remains uncertain whether this relationship holds true in the context of NAFLD in humans. We compared fasting serum ß-HB levels with direct measurement of liver mitochondrial palmitate oxidation in humans stratified based on NAFLD severity (n = 142). Patients were stratified based on NAFLD activity score (NAS): NAS = 0 (no disease), NAS = 1-2 (mild), NAS = 3-4 (moderate), and NAS ≥ 5 (advanced). Moderate and advanced NAFLD is associated with reductions in liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), serum ß-HB, but not 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) mRNA, relative to no disease. Worsening liver mitochondrial complete palmitate oxidation corresponded with lower HMGCS2 mRNA but not total (complete + incomplete) palmitate oxidation. Interestingly, we found that liver HMGCS2 mRNA and serum ß-HB correlated with liver mitochondrial ß-hydroxyacyl-CoA dehydrogenase (ß-HAD) activity and CPT1A mRNA. Also, lower mitochondrial mass and markers of mitochondrial turnover positively correlated with lower HMGCS2 in the liver. These data suggest that liver ketogenesis and FAO occur at comparable rates in individuals with NAFLD. Our findings support the utility of serum ß-HB to serve as a marker of liver injury and hepatic FAO in the context of NAFLD.NEW & NOTEWORTHY Serum ß-hydroxybutyrate (ß-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating ß-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum ß-HB. Our work supports serum ß-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD.

BACKGROUND AND AIMS: NAFLD and its more-advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver-related, and all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant. APPROACH AND RESULTS: To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline-NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite-NASH (D-NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO2 and the rate-limiting enzyme in ß-oxidation (ß-hydroxyacyl-CoA dehydrogenase activity) were reduced by ~40%-50% with D-NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH. CONCLUSIONS: These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.

Daily mindfulness, negative affect, and eating behaviors in adolescents at risk for excess weight gain.

OBJECTIVE: Loss-of-control and overeating are common in adolescents with high body mass index (BMI). Mindfulness may affect negative affect, and both may relate to loss-of-control and overeating. Yet, there is limited understanding of these associations in adolescents' daily lives. METHODS: Forty-five adolescents (77% female; Mage = 14.4 years, SDage = 1.7 years) with high weight (92% with BMI [kg/m2 ] ≥85th percentile for age/sex) provided daily, repeated measurements of mindfulness, negative affect, loss-of-control, and overeating for ~7 days (M = 5.6 days; range = 1-13). Multilevel mixed modeling was conducted to test within-person (intraindividual) and between-person (interindividual) associations for the same-day (concurrent) and next-day (time-ordered/prospective). RESULTS: There were within-person and between-person associations of higher mindfulness with lower negative affect on the same-day and next-day. Greater between-person mindfulness related to lower odds of adolescents' loss-of-control occurrence (same-day) and conversely, more perceived control over eating (same-day and next-day). Greater within-person mindfulness related to less odds of next-day overeating. DISCUSSION: Dynamic relations exist among mindfulness, negative affect, and eating in adolescents at-risk for excess weight gain. Mindfulness may be an important element to consider in loss-of-control and overeating. Future work using momentary-data within an experimental design would help disentangle the intraindividual effects of increasing mindfulness/decreasing negative affect on disordered eating. PUBLIC SIGNIFICANCE: Loss-of-control and overeating are common in teenagers with high weight. Greater mindfulness-present-moment, non-judgmental attention-and less negative emotions may relate to healthier eating, but we do not know how these processes play out in teenagers' daily lives. Addressing this knowledge gap, the current findings showed that greater daily mindfulness, but not negative affect, related to less loss-of-control/overeating, suggesting the importance of mindfulness for eating patterns in teenagers' daily lives.

Observations of parent-adolescent interactions relate to food parenting practices and adolescent disordered eating in adolescents at risk for adult obesity.

Adolescent disordered eating and obesity are interrelated and adversely relate to mental and metabolic health. Parental feeding practices have been associated with adolescent disordered eating and obesity. Yet, observable interactions related to food parenting have not been well characterized. To address this gap, N = 30 adolescents (M ± SD 14 ± 2 year) at risk for adult obesity due to above-average body mass index (BMI ≥70th percentile) or parental obesity (BMI ≥30 kg/m2 ) participated in a video-recorded parent-adolescent task to discuss a food/eating-related disagreement. Interactions were coded for individual/dyadic affect/content using the Interactional Dimensions Coding System. We examined associations of interaction qualities with parent-reported food practices, adolescent disordered eating behaviors/attitudes, and insulin resistance. Reported parenting practices were correlated with multiple interaction qualities (p-values <0.05), with the most consistent correspondence between parent-reported pressure to eat (e.g., pressure to eat more healthy foods) and negative aspects of parent-adolescent interactions. Also, after accounting for adolescent age, sex, and BMI-standard score, parent-adolescent interaction qualities were associated with adolescents' disordered eating and insulin resistance. Specifically, greater adolescent problem-solving related to less adolescent global disordered eating, shape, and weight concern (p-values <0.05); adolescent autonomy related to less weight concern (p = 0.03). Better parent communication skills were associated with less adolescent eating concern (p = 0.04), and observed dyadic mutuality related to adolescents' lower insulin resistance (p = 0.03). Parent-adolescent interaction qualities during food/eating-related disagreements show associations with parent-reported food practices and adolescent disordered eating. This method may offer a tool for measuring the qualities of parent-adolescent food/eating-related interactions. A nuanced understanding of conversations about food/eating may inform family-based intervention in youth at-risk for adult obesity.

Virus filtration: A review of current and future practices in bioprocessing.

For drug products manufactured in mammalian cells, safety assurance practices are needed during production to assure that the final medicinal product is safe from the potential risk of viral contamination. Virus filters provide viral retention for a range of viruses through robust, largely size-based retention mechanism. Therefore, a virus filtration step is commonly utilized in a well-designed recombinant therapeutic protein purification process and is a key component in an overall strategy to minimize the risks of adventitious and endogenous viral particles during the manufacturing of biotechnology products. This study summarizes the history of virus filtration, currently available virus filters and prefilters, and virus filtration integrity test methods and study models. There is also discussion of current understanding and gaps with an eye toward future trends and emerging filtration technologies.

Climate change winners and losers among North American bumblebees.

Mounting evidence suggests that climate change, agricultural intensification and disease are impacting bumblebee health and contributing to species' declines. Identifying how these factors impact insect communities at large spatial and temporal scales is difficult, partly because species may respond in different ways. Further, the necessary data must span large spatial and temporal scales, which usually means they comprise aggregated, presence-only records collected using numerous methods (e.g. diversity surveys, educational collections, citizen-science projects, standardized ecological surveys). Here, we use occupancy models, which explicitly correct for biases in the species observation process, to quantify the effect of changes in temperature, precipitation and floral resources on bumblebee site occupancy over the past 12 decades in North America. We find no evidence of genus-wide declines in site occupancy, but do find that occupancy is strongly related to temperature, and is only weakly related to precipitation or floral resources. We also find that more species are likely to be climate change 'losers' than 'winners' and that this effect is primarily associated with changing temperature. Importantly, all trends were highly species-specific, highlighting that genus or community-wide measures may not reflect diverse species-specific patterns that are critical in guiding allocation of conservation resources.

Rodent mnemonic similarity task performance requires the prefrontal cortex.

Mnemonic similarity task performance, in which a known target stimulus must be distinguished from similar lures, is supported by the hippocampus and perirhinal cortex. Impairments on this task are known to manifest with advancing age. Interestingly, disrupting hippocampal activity leads to mnemonic discrimination impairments when lures are novel, but not when they are familiar. This observation suggests that other brain structures support discrimination abilities as stimuli are learned. The prefrontal cortex (PFC) is critical for retrieval of remote events and executive functions, such as working memory, and is also particularly vulnerable to dysfunction in aging. Importantly, the medial PFC is reciprocally connected to the perirhinal cortex and neuron firing in this region coordinates communication between lateral entorhinal and perirhinal cortices to presumably modulate hippocampal activity. This anatomical organization and function of the medial PFC suggests that it contributes to mnemonic discrimination; however, this notion has not been empirically tested. In the current study, rats were trained on a LEGO object-based mnemonic similarity task adapted for rodents, and surgically implanted with guide cannulae targeting prelimbic and infralimbic regions of the medial PFC. Prior to mnemonic discrimination tests, rats received PFC infusions of the GABAA agonist muscimol. Analyses of expression of the neuronal activity-dependent immediate-early gene Arc in medial PFC and adjacent cortical regions confirmed muscimol infusions led to neuronal inactivation in the infralimbic and prelimbic cortices. Moreover, muscimol infusions in PFC impaired mnemonic discrimination performance relative to the vehicle control across all testing blocks when lures shared 50-90% feature overlap with the target. Thus, in contrast hippocampal infusions, PFC inactivation impaired target-lure discrimination regardless of the novelty or familiarity of the lures. These findings indicate the PFC plays a critical role in mnemonic similarity task performance, but the time course of PFC involvement is dissociable from that of the hippocampus.

Analysis of Prehospital Administration of Blood Products to Pediatric Casualties in Iraq and Afghanistan.

BACKGROUND: Hemorrhage is one of the leading causes of preventable death in both military and civilian trauma. Implementation of items such as tourniquets and hemostatic dressings are helpful in controlling hemorrhage and increasing the survival rate of casualties when such injuries occur. Prehospital blood transfusions are used to treat patients with severe injuries where the standard methods of hemorrhage control are not an effective form of treatment. There is limited research and no widely accepted protocol on pediatric prehospital blood transfusions. METHODS: We queried the Department of Defense Trauma Registry (DODTR) for all pediatric subjects admitted to U.S. and Coalition fixed-facility hospitals in Iraq and Afghanistan from January 2007 to January 2016. This is a secondary analysis of casualties that received blood products prehospital. RESULTS: From January 2007 through January 2016 there were 3439 pediatric casualties within the registry. Within this group, 22 casualties that received one or more blood product prehospital were identified. Children in the 10-14 years age (40%) group made up the largest proportion, 86% were male, almost all were injured by explosive (63%) or firearm (27%), and 77% survived to hospital discharge. The most frequently administered blood product was packed red cells (n = 17). Of the 22, 15 underwent massive transfusion within the first 24 hours of admission. CONCLUSIONS: Prehospital administration of blood products occurred infrequently within this pediatric dataset, but those that received blood were critically injured with most receiving a massive transfusion. Given the frequency with which medical personnel are carrying blood products in the prehospital, combat setting, guidelines specific to pediatric administration would be beneficial.

The role of mindfulness in associations among depression symptoms, sleep duration, and insulin resistance in adolescents.

Sleep difficulties may be one explanatory factor in the association between depression and insulin resistance; yet, explicit tests of this hypothesis are lacking. We determined if there was an indirect effect of depression symptoms on insulin resistance through sleep duration in adolescents at risk for excess weight gain. We also investigated whether dispositional mindfulness moderated the interconnections among depression, sleep, and insulin resistance. Ninety adolescents (14.2 ± 1.6y; 50% female) at risk for excess weight gain (body mass index [BMI, kg/m2] z score 1.6 ± 0.6) participated in the cross-sectional, baseline phase of a health behaviors study. Depression was assessed with the Center for Epidemiologic Studies-Depression Scale, sleep duration with the Sleep Habits Survey, and mindfulness with the Mindful Attention and Awareness Scale. Homeostatic model assessment of insulin resistance was determined from fasting insulin and glucose. The product-of-coefficients method was used to test the indirect effect of depression on insulin resistance through sleep duration, accounting for age, sex, BMIz, puberty, and socioeconomic status (SES). Dispositional mindfulness was tested as a moderator of the associations among depression, sleep, and insulin resistance. There was a significant indirect effect of depression on insulin resistance through sleep duration, controlling for age, sex, BMIz, puberty, and SES, 95%CI [0.001, 0.05]. Dispositional mindfulness moderated the association between sleep duration and insulin resistance, such that lower sleep duration related to greater insulin resistance only among adolescents with lower mindfulness (p < .001). Short sleep may be one explanatory factor in the depression-insulin resistance connection in adolescents at risk for excess weight gain. Adolescents with poorer mindfulness and short sleep are at highest risk for insulin resistance, whereas higher mindfulness may be protective.

How It Started, and How It's Going: Global Family Planning Programs.

Family planning (FP) is the domain that enables people to have their desired number of children if any, and the desired spacing of births. FP initiatives are cross-cutting approaches to empower people with human and reproductive rights, lessen child morbidity and pregnancy-related morbidity and mortality, alleviate poverty, slow climate change, provide sustainable economic growth and development, advance education, and voluntarily slow overpopulation. We examine global FP programs: the history, drivers, and indicators to measure impact, policy, and strategy that surrounds human reproduction. We focus on current trends of task-sharing, self-care, digital health solutions, and the ever-changing contexts with our current pandemic of coronavirus disease 2019.

Associations of adverse childhood experiences with stress physiology and insulin resistance in adolescents at risk for adult obesity.

Adverse childhood experiences (ACEs) heighten the risk for adult obesity and cardiometabolic disease, but physiological factors underlying this connection are not well understood. We determined if ACEs were associated with physiological stress response and insulin resistance in adolescents at risk for adult obesity. Participants were 90 adolescents 12.0-17.5 years (50% female, 30% Hispanic/Latinx), at risk for adult obesity by virtue of above-average body mass index (BMI; kg/m2 ≥ 70th percentile) or parental obesity (BMI ≥ 30 kg/m2 ). ACEs were determined as presence (vs. absence) based upon the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Physiological stress response was measured as heart rate/blood pressure response to the Trier Social Stress Test. Homeostatic model assessment of insulin resistance was determined from fasting glucose/insulin. Sixty-one percent of adolescents reported positive ACE history. The presence of ACEs predicted greater heart rate (p < .001) and diastolic blood pressure (p = .02) response to stress, controlling for age, sex, race/ethnicity, puberty, and BMI standard score. Systolic blood pressure and insulin resistance did not differ by ACE history (p-values > .08). Findings suggest heightened sympathetic stress response in adolescence could be explanatory in how ACEs increase the risk for later cardiometabolic disease. Future studies should characterize ACEs in relationship to day-to-day variations in adolescents' stress physiology and glucose homeostasis.

Examining the Gastrointestinal and Immunomodulatory Effects of the Novel Probiotic Bacillus subtilis DE111.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain-specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a pilot randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-intervention, as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an increase in anti-inflammatory immune cell populations in response to ex vivo LPS stimulation of PBMCs in the DE111 intervention group. Overall perceived gastrointestinal health, microbiota, and circulating and fecal markers of inflammation (Il-6, sIgA) and gut barrier function (plasma zonulin) were largely unaffected by DE111 intervention, although the study may have been underpowered to detect these differences. These pilot data provide information and justification to conduct an appropriately powered clinical study to further examine the immunomodulatory potential of B. subtilis DE111 in human populations.

Microbial metabolite indole-3-propionic acid supplementation does not protect mice from the cardiometabolic consequences of a Western diet.

Emerging evidence suggests that intestinal microbes regulate host physiology and cardiometabolic health, although the mechanism(s) by which they do so is unclear. Indoles are a group of compounds produced from bacterial metabolism of the amino acid tryptophan. In light of recent data suggesting broad physiological effects of indoles on host physiology, we examined whether indole-3-propionic acid (IPA) would protect mice from the cardiometabolic consequences of a Western diet. Male C57BL/6J mice were fed either a standard diet (SD) or Western diet (WD) for 5 mo and received normal autoclaved drinking water or water supplemented with IPA (0.1 mg/mL; SD + IPA and WD + IPA). WD feeding led to increased liver triglycerides and makers of inflammation, with no effect of IPA. At 5 mo, arterial stiffness was significantly higher in WD and WD + IPA compared with SD (WD: 485.7 ± 6.7 and WD + IPA: 492.8 ± 8.6 vs. SD: 436.9 ± 7.0 cm/s, P < 0.05) but not SD + IPA (SD + IPA: 468.1 ± 6.6 vs. WD groups, P > 0.05). Supplementation with IPA in the SD + IPA group significantly increased glucose AUC compared with SD mice (SD + IPA: 1,763.3 ± 92.0 vs. SD: 1,397.6 ± 64.0, P < 0.05), and no significant differences were observed among either the WD or WD + IPA groups (WD: 1,623.5 ± 77.3 and WD + IPA: 1,658.4 ± 88.4, P > 0.05). Gut microbiota changes were driven by WD feeding, whereas IPA supplementation drove differences in SD-fed mice. In conclusion, supplementation with IPA did not improve cardiometabolic outcomes in WD-fed mice and may have worsened some parameters in SD-fed mice, suggesting that IPA is not a critical signal mediating WD-induced cardiometabolic dysfunction downstream of the gut microbiota.NEW & NOTEWORTHY The gut microbiota has been shown to mediate host health. Emerging data implicate gut microbial metabolites of tryptophan metabolism as potential important mediators. We examined the effects of indole-3-propionic acid in Western diet-fed mice and found no beneficial cardiometabolic effects. Our data do not support the supposition that indole-3-propionic acid (IPA) mediates beneficial metabolic effects downstream of the gut microbiota and may be potentially deleterious in higher circulating levels.

Associations of parental feeding practices and food reward responsiveness with adolescent stress-eating.

Rates of adolescent obesity have continued to rise over the past decade. As adolescence is an important time for developing eating habits that endure into adulthood, more information is needed about the potentially modifiable family- and individual-level factors that influence the development of common overeating behaviors such as stress-eating during adolescence. In this study, we conducted secondary data analyses to evaluate how parental feeding practices and adolescents' food reward responsiveness related to adolescents' stress-eating during a laboratory test meal. Participants were 90 healthy adolescents (50% female), 12-17 years of age (M = 14.3, SD = 1.7 years), at risk for excess weight gain (BMI percentile M = 92.7, SD = 7.5). Parental feeding behaviors were assessed with parent-report on the Child Feeding Questionnaire-Adolescent Version. Adolescents' relative reward value of food was measured with a behavioral task. Stress-eating was assessed as total energy intake from a buffet lunch meal after adolescents participated in the Trier Social Stress Test adapted for adolescents. Results revealed that parental concern about their child's weight (t = 2.27, p = .02) and adolescents' relative reward value of food (t = 2.24, p = .03) were related to greater stress-eating, controlling for BMI standard score, age, sex, and general perceived stress. Parental restriction was not related to stress-eating in this sample (p = .21). These findings suggest that parental attitudes about their adolescent's weight and adolescents' own internalized responsiveness to food as a reward may play a role in propensity to engage in overeating in response to stress.

Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults.

Cannabidiol (CBD) is a dietary supplement with numerous purported health benefits and an expanding commercial market. Commercially available CBD preparations range from tinctures, oils, and powders, to foods and beverages. Despite widespread use, information regarding bioavailability of these formulations is limited. The purpose of this study was to test the bioavailability of two oral formulations of CBD in humans and explore their potential acute anti-inflammatory activity. We conducted a pilot randomized, parallel arm, double-blind study in 10 healthy adults to determine differences in pharmacokinetics of commercially available water and lipid-soluble CBD powders. Participants consumed a single 30 mg dose, which is within the range of typical commercial supplement doses, and blood samples were collected over 6 hr and analyzed for CBD concentrations. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and T = 90 min, cultured and stimulated with bacterial lipopolysaccharide (LPS) to induce an inflammatory response. Cell supernatants were assayed for IL-10 and TNF, markers of inflammation, using enzyme-linked immunosorbent assays. The water-soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid-soluble form. TNF was decreased in LPS-stimulated PBMCs collected 90 min after CBD exposure relative to cells collected at baseline. This study provides pilot data for designing and powering future studies to establish the anti-inflammatory potential and bioavailability of a larger variety of commercial CBD products consumed by humans.

Mindfulness-based group intervention in adolescents at-risk for excess weight gain: A randomized controlled pilot study.

OBJECTIVES: To assess feasibility/acceptability of a mindfulness-based approach to excess weight prevention in adolescents at-risk for excess weight gain. To pilot test efficacy of a mindfulness-based intervention for improving food reward sensitivity, stress-eating, executive function (EF), and BMI/adiposity. METHODS: A pilot randomized controlled trial was conducted with 12-17y adolescents at-risk for excess weight gain based on above-average weight (body mass index [BMI]≥70%ile) or parental history of obesity (BMI≥30 kg/m2). Adolescents were randomized to a mindfulness-based (n = 29) or health education control group (n = 25) that met for six weekly one-hour sessions. Feasibility/acceptability were determined from attendance and acceptability survey ratings. At baseline, six-week and six-month follow-up, adolescents' perceived stress was measured with the Perceived Stress Scale, food reward sensitivity with a behavioral task, stress-eating during a laboratory test meal, and EF with the parent-reported Behavior Rating Inventory of Executive Function and NIH Toolbox. At the same intervals, BMI indices and body fat by air displacement plethysmography were assessed in a fasted state. RESULTS: Median session attendance was 6:6 sessions in both conditions; program acceptability ratings were above-average. Compared to health education, adolescents in mindfulness had lower food reward sensitivity at six-months (Cohen's d = 0.64, p = .01). There were no between-condition differences in BMI (mindfulness vs. health educationΔsix-months 95%CI 0.20, 1.52 kg/m2 vs. 0.21, 1.62 kg/m2) or adiposity (-3.64, -0.61% vs. -4.31, -1.04%) changes. CONCLUSIONS: A mindfulness-based group intervention is feasible/acceptable among adolescents at-risk for excess weight. In this pilot sample, mindfulness and health education were equivocal for BMI/adiposity outcomes. Future trials with a larger, adequately-powered sample and longer-term follow-up are necessary to test efficacy of a mindfulness-based intervention for food reward sensitivity, stress-eating, EF, and stabilizing growth trajectories in youth at-risk for adult obesity.

Artificial Domicile Use by Bumble Bees (Bombus; Hymenoptera: Apidae) in Ontario, Canada.

Bumble bees are an important group of pollinating insects that are of increasing conservation concern due to relatively recent and dramatic species-specific declines. Nesting ecology can vary significantly between species, and nest site selection may be affected by many factors, including heredity, individual experience, and habitat availability. Data on bumble bee nesting ecology are inherently difficult to collect in the wild as nests are often cryptic. Artificial domiciles (nest boxes) can be a useful tool for gathering information on species-specific nesting behavior to inform conservation management of native pollinator populations. The aim of this study was to examine the use of three different domicile designs for monitoring bumble bees: aboveground, underground, and false underground, while collecting information on occupying species identity and richness to compare with sampling with traditional netting survey methods. Across Ontario, the majority of sites had at least one domicile occupied, with the aboveground installation method proving most successful whereas no false-underground domiciles were occupied. Occupied domiciles appeared to preferentially sample certain species compared to netting surveys, and rarefied species richness of both methods was similar. Given that some bumble bees did occupy artificial domiciles, and species richness relative to sample size was high, with further refinement, this method may be useful for bumble bee research and monitoring: filling in nesting ecology knowledge gaps and potentially as a conservation management tool.

Regulation of mitochondrial trifunctional protein modulates nonalcoholic fatty liver disease in mice.

Mitochondrial trifunctional protein (MTP) plays a critical role in the oxidation of long-chain fatty acids. We previously reported that aging mice (>9 months old) heterozygous for an MTP defect (MTP+/-) develop nonalcoholic fatty liver disease (NAFLD). We tested whether a high-fat diet (HFD) accelerates NAFLD in young MTP+/-mice, and whether overexpression of the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuin 3 (SIRT3) deacetylates MTP and improves mitochondrial function and NAFLD. Three-month-old WT and MTP+/- mice were fed HFD (60% cal fat) for 16 weeks and livers were assessed for fatty acid oxidation (FAO) and NAFLD. Compared with WT, MTP+/- mice displayed reduced hepatic SIRT3 levels and reduced FAO, with increased hepatic steatosis and the inflammatory marker CD68. Hepatic overexpression of SIRT3 in HFD-fed MTP+/- mice increased hepatic MTP protein levels at the posttranscriptional level. Immunoprecipitation of MTP from liver mitochondria followed by Western blot with acetyl-lysine antibody showed higher acetylation of MTP in MTP+/- compared with WT mice. Overexpression of SIRT3 in MTP+/- mice significantly reduced the acetylation of MTP compared with ß-galactosidase controls, increased mitochondrial FAO, and reduced hepatic steatosis, CD68, and serum ALT levels. Taken together, our data indicate that deacetylation of MTP by SIRT3 improves mitochondrial function and rescues NAFLD in MTP+/- mice.