Neonatal Exendin-4 Reduces Growth,Fat Deposition and Glucose Tolerance during Treatment in the Intrauterine Growth-Restricted Lamb

Background

IUGR increases the risk of type 2 diabetes mellitus (T2DM) in later life, due to reduced insulin sensitivity and impaired adaptation of insulin secretion. In IUGR rats, development of T2DM can be prevented by neonatal administration of the GLP-1 analogue exendin-4. We therefore investigated effects of neonatal exendin-4 administration on insulin action and β-cell mass and function in the IUGR neonate in the sheep, a species with a more developed pancreas at birth.

Methods

Twin IUGR lambs were injected s.c. daily with vehicle (IUGR+Veh, n = 8) or exendin-4 (1 nmol.kg^-1, IUGR+Ex-4, n = 8), and singleton control lambs were injected with vehicle (CON, n = 7), from d 1 to 16 of age. Glucose-stimulated insulin secretion and insulin sensitivity were measured in vivo during treatment (d 12–14). Body composition, β-cell mass and in vitro insulin secretion of isolated pancreatic islets were measured at d 16.

Principal Findings

IUGR+Veh did not alter in vivo insulin secretion or insulin sensitivity or β-cell mass, but increased glucose-stimulated insulin secretion in vitro. Exendin-4 treatment of the IUGR lamb impaired glucose tolerance in vivo, reflecting reduced insulin sensitivity, and normalised glucose-stimulated insulin secretion in vitro. Exendin-4 also reduced neonatal growth and visceral fat accumulation in IUGR lambs, known risk factors for later T2DM.

Conclusions

Neonatal exendin-4 induces changes in IUGR lambs that might improve later insulin action. Whether these effects of exendin-4 lead to improved insulin action in adult life after IUGR in the sheep, as in the PR rat, requires further investigation.     

Bisphenol A Impairs Hepatic Glucose Sensing in C57BL/6 Male Mice

Aims/Hypothesis

Glucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly.

Methods

To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5) vs. water alone (n = 5) was administered at the EPA’s purported “safe dose” (50 µg/kg) by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1–20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15) or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14) for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above.

Results

Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002–0.029 at glucose 5–20 mmol/l; overall treatment effect p<0.001). Exposure to BPA over 2 weeks also suppressed hepatic glucokinase activity in exposed vs. unexposed mice (overall treatment effect, p = 0.003). In both experiments, the Hill coefficient was higher and Vmax lower in mice treated with BPA.

Conclusions/Interpretation

Both acute and chronic exposure to BPA significantly impair hepatic glucokinase activity and function. These findings identify a potential mechanism for how BPA may increase risk for diabetes.     

Improving Metabolic Health in Obese Male Mice via Diet and Exercise Restores Embryo Development and Fetal Growth

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.     

Trauma History and Depression Predict Incomplete Adherence to Antiretroviral Therapies in a Low Income Country

Background

As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care.

Methodology

The Coping with HIV/AIDS in Tanzania (CHAT) study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+) participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N = 468). Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART.

Results

Incomplete ART adherence was significantly more likely to be reported amongst participants who experienced a greater number of childhood traumatic events: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD). In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence.

Discussion

This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of expanded antiretroviral access to improve health and reduce new infections.     

Risk-taking in free-living spotted hyenas is associated with anthropogenic disturbance,predicts survivorship,and is consistent across experimental contexts

Anthropogenic disturbance can have important influences on the fitness and behaviors of wild animals, including their boldness when exposed to risky conditions. We presented spotted hyenas (Crocuta crocuta) from two populations, each exposed to a different level of human activity, with a life-size model hyena representing an intruder from another clan. The high-disturbance population lived adjacent to human settlements, and the low-disturbance population inhabited a relatively undisturbed part of the same national park in Kenya. The mock intruder was presented to individual hyenas to assess their reactions to an alien hyena, and to determine whether their reactions varied with their exposure to anthropogenic activity. We found that human disturbance was indeed associated with hyena risk-taking behavior in response to the model intruder. Hyenas tested in the low-disturbance area exhibited more risk-taking behaviors by approaching the mock intruder more closely, and spending more time near it, than did their counterparts living in high-disturbance areas. Hyenas that spent less time in close proximity to the model had greater survivorship than those that spent more time in close proximity to it, regardless of disturbance level. Furthermore, the individual differences in risk-taking measured here were consistent with those obtained previously from the same animals using a different set of experimental manipulations. However, the experimentally induced behaviors were not consistent with naturally occurring risk-taking behaviors in proximity to lions; this suggests that risk-taking behaviors are consistent within individuals across experimental contexts, but that exposure to lions elicits different responses. Although our results are consistent with those from earlier tests of anthropogenic disturbance and boldness in spotted hyenas and other predators, they differ from results obtained from birds and small mammals, which are generally found to be bolder in areas characterized by human disturbance.     

Fossil liberation: a model to explain high biodiversity in the Triassic Cassian Formation

With 1429 animal species, the Triassic Cassian Formation in the Dolomites, Southern Alps (Italy), yields the highest species richness reported from any spatially constrained pre-Quaternary formation known to science. The high preserved diversity is partly attributable to a high primary diversity governed by the tropical setting, increasing alpha diversity, and the breadth of habitats spurring beta diversity. More important is the excellent preservation of fossils and the ease with which they can be extracted from the poorly lithified sediments. We propose the term ‘liberation Lagerstätten’ to capture this preservational window. In contrast to conservation Lagerstätten, liberation Lagerstätten like the Cassian Formation originate from normal marine conditions but low-grade diagenesis. Molluscs contribute substantially to species richness, comprising 67% of all invertebrate species in the Cassian Formation. The gastropod dominance (39% of all species) is nearly as great as in Recent tropical settings, contradicting the concept of a substantial Cenozoic rise.     

Early effects of temperate agroforestry practices on soil organic matter and microbial enzyme activity

Plant and Soil - A field experiment was conducted to evaluate the effects of alley cropping systems on microbial activity and soil organic matter (SOM) pools. We hypothesized that enzyme activity...     

Simulated and experimental estimates of hydrodynamic drag from bio-logging tags

Drag force acting on swimming marine mammals is difficult to measure directly. Researchers often use simple modeling and kinematic measurements from animals, or computational fluid dynamics (CFD) simulations to estimate drag. However, studies that compare these methods are lacking. Here, computational simulation and physical experiments were used to estimate drag forces on gliding bottlenose dolphins (Tursiops truncatus). To facilitate comparison, variable drag loading (no-tag, tag, tag + 4, tag + 8) was used to increase force in both simulations and experiments. During the experiments, two dolphins were trained to perform controlled glides with variable loading. CFD simulations of dolphin/tag geometry in steady flow (1–6 m/s) were used to model drag forces. We expect both techniques will capture relative changes created by experimental conditions, but absolute forces predicted by the methods will differ. CFD estimates were within a calculated 90% confidence interval of the experimental results for all but the tag condition. Relative drag increase predicted by the simulation vs. experiment, respectively, differed by between 21% and 31%: tag, 4% vs. 33%; tag + 4, 47% vs. 68%; and tag + 8, 108% vs. 77%. The results from this work provide a direct comparison of computational and experimental estimates of drag, and provide a framework to quantify uncertainty.     

The incidence of turnip yellows virus in oilseed rape crops (Brassica napus L.) in three different regions of England over three consecutive growing seasons and the relationship with the abundance of flying Myzus persicae

Turnip yellows virus (TuYV) is the most important virus infecting oilseed rape in the United Kingdom. The incidence and spatial distribution of TuYV in winter oilseed rape (WOSR) crops in three regions of England were determined over three growing seasons. Leaf samples were collected from three fields in each region, in autumn (November–December) and spring (April) of the three crop seasons and tested for virus presence by enzyme-linked immunosorbent assay. Infection was detected in all fields except one. Higher TuYV incidences were recorded in 2007–2008 (≤89%) and 2009–2010 (≤100%) crop seasons than in 2008–2009 (≤24%). Highest incidences were recorded in Lincolnshire (≤100%), followed by Warwickshire (≤88%), with lowest incidences in Yorkshire (1–74%). There was a significant increase in incidence detected between autumn and spring sampling in eight fields, a significant decrease in one field and no significant change in 18 fields. Rothamsted Insect Survey suction trap data for the aphid Myzus persicae in Lincolnshire, Warwickshire and Yorkshire revealed two peaks of flight activity in most years (2007–2009). The second peak (September–November) coincided with emergence of WOSR. The highest cumulative (August–November) trap catches in the three regions during the three crop seasons occurred in Lincolnshire and the lowest in Yorkshire; catches in autumn 2009 were highest and lowest in autumn 2008. Regression analysis revealed a highly significant association between the cumulative numbers of M. persicae caught in the suction traps closest to the crops between August and November each year and the incidence of TuYV detected in the WOSR crops in the autumn of each year. Results are discussed in the light of factors affecting the spread of TuYV and future possibilities for control.