Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep

Epidemiological and experimental studies suggest early nutrition has long-term effects on susceptibility to obesity, cardiovascular and metabolic diseases. Small and large animal models confirm the influence of different windows of sensitivity, from fetal to early postnatal life, on offspring phenotype. We showed previously that undernutrition in sheep either during the first month of gestation or immediately after weaning induces differential, sex-specific changes in adult metabolic and cardiovascular systems. The current study aims to determine metabolic and molecular changes that underlie differences in lipid and glucose metabolism induced by undernutrition during specific developmental periods in male and female sheep. Ewes received 100% (C) or 50% nutritional requirements (U) from 1–31 days gestation, and 100% thereafter. From weaning (12 weeks) to 25 weeks, offspring were then fed either ad libitum (CC, UC) or were undernourished (CU, UU) to reduce body weight to 85% of their individual target. From 25 weeks, all offspring were fed ad libitum. A cohort of late gestation fetuses were studied after receiving either 40% nutritional requirements (1–31 days gestation) or 50% nutritional requirements (104–127 days gestation). Post-weaning undernutrition increased in vivo insulin sensitivity, insulin receptor and glucose transporter 4 expression in muscle, and lowered hepatic methylation at the delta-like homolog 1/maternally expressed gene 3 imprinted cluster in adult females, but not males. Early gestational undernutrition induced lower hepatic expression of gluconeogenic factors in fetuses and reduced in vivo adipose tissue insulin sensitivity in adulthood. In males, undernutrition in early gestation increased adipose tissue lipid handling mechanisms (lipoprotein lipase, glucocorticoid receptor expression) and hepatic methylation within the imprinted control region of insulin-like growth factor 2 receptor in adulthood. Therefore, undernutrition during development induces changes in mechanisms of lipid and glucose metabolism which differ between tissues and sexes dependent on the period of nutritional restriction. Such changes may increase later life obesity and dyslipidaemia risk

Engaging Low-Income Parents in Childhood Obesity Prevention from Start to Finish: A Case Study

Prevention of childhood obesity is a national priority. Parents influence young children’s healthy lifestyles, so it is paradoxical that obesity interventions focus primarily on children. Evidence and theory suggest that including parents in interventions offers promise for effective childhood obesity prevention. This case study engaged parents’ as co-researchers in the design, implementation and evaluation of an intervention for low-income families with a child enrolled in Head Start. Parent engagement mechanisms include: (1) targeted partnership development (2) operationalizing a Community Advisory Board (CAB) that was the key decision making body; (3) a majority of CAB members were parents who were positioned as experts, and (4) addressing structural barriers to parent participation. Lessons learned are provided for future research, and practice

Reduced fetal vitamin D status by maternal undernutrition during discrete gestational windows in sheep

Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport (aromatic T-type amino acid transporter-1 [TAT-1]; triglyceride hydrolase / lipoprotein uptake facilitator lipoprotein lipase [LPL]) and vitamin D homeostasis (CYP27B1; vitamin D receptor [VDR]), and their association with markers of fetal cardiovascular function and skeletal muscle growth. Pregnant sheep received 100% total metabolizable energy (ME) requirements (control), 40% total ME requirements peri-implantation (PI40, 1–31 days of gestation [dGA]) or 50% total ME requirements in late gestation (L, 104–127 dGA). Fetal, but not maternal, plasma 25-hydroxy-vitamin D (25OHD) concentration was lower in PI40 and L maternal undernutrition groups (p<0.01) compared with the control group at 0.86 gestation. PI40 group placental CYP27B1 mRNA levels were increased (p<0.05) compared with the control group. Across all groups, higher fetal plasma 25OHD concentration was associated with higher skeletal muscle myofibre and capillary density (p<0.05). In the placenta, higher VDR mRNA levels were associated with higher TAT-1 (p<0.05) and LPL (p<0.01) mRNA levels. In the PI40 maternal undernutrition group only, reduced fetal plasma 25OHD concentration may be mediated in part by altered placental CYP27B1. The association between placental mRNA levels of VDR and nutrient transport genes suggests a way in which the placenta may integrate nutritional cues in the face of maternal dietary challenges and alter fetal physiology

Pregnancy-associated cardiomyopathy in survivors of childhood cancer

Current information regarding pregnancy-associated cardiomyopathy among women treated for childhood cancer is insufficient to appropriately guide counseling and patient management. This study aims to characterize its prevalence within a large cohort of females exposed to cardiotoxic therapy

Investigating factors that support and challenge in implementing authentic research experiences for undergraduates

KEYWORDS: undergraduate, research experience, course integrated, implementation, case study, science This study investigated the implementer experience of introducing an Authentic Large Scale Undergraduate Research Experience (ALURE) into 7 science courses in three Australian tertiary institutions. The results will be of value to tertiary science educators who are interested in giving the opportunity to experience the benefits of research participation to a larger number of their undergraduate students. BACKGROUND The integration of research experiences into undergraduate curricula is of special importance in the fields of STEM. Engaging undergraduate students in research is considered essential for a tertiary science education, informing students future career course and increasing student retention. Our project is supporting the introduction of an ALURE (Authentic Large Scale Undergraduate Research Experience) practical into several undergraduate science courses. These ALURE practicals are designed to overcome the cohort size limits of the research internship model primarily due to their integration to the course based practical session. ALUREs are designed to give whole cohorts of students a chance to take part in an undergraduate research experience throughout their education; giving students an idea of what real research is before they enter into post-graduate life. Our team has previously documented several ALURE practicals reported in several papers (Rowland, Lawrie, Behrendorff & Gillam 2012; Wang, Schembri, Ramakrishna, Sagulenko & Fuerst, 2012); this allows us to act as mentors to new ALURE implementers during our OLT-funded Leadership for Excellence Project. AIMS This study aimed to document the experience of implementers during the delivery of an ALURE and determine what factors supported and challenged them during this time. The aim of the ALURE Project is to provide leadership and mentoring to any academics wanting to engage their undergraduates in course integrated research experiences. We aim to utilise this data to amend and improve current guidelines of ALURE implementation to define a best practice for the future. DESCRIPTION OF STUDY This year, ALUREs were implemented at various tertiary institutions nationally in courses covering a broad range of scientific disciplines including biochemistry, nanotechnology and microbiology. The implementers of these programs are the topic of this study and their experiences provide deeper insight into the potential hurdles to integrating a large-scale course based URE. Implementers that were investigated included course coordinators, laboratory demonstrators and preparation staff. The study included 7 different science courses across 4 Australian tertiary institutions. DESIGN AND METHODS This narrative and grounded theory mixed methods study drew from qualitative sources of information in the form of recorded interviews with implementers from 4 Australian universities invited to share their experience. Transcripts were coded to find common themes in order to discover the factors that challenged and supported the introduction of ALURE into their course. RESULTS Preliminary data shows that currently the main challenging factor is the time taken to implement these practicals into the course for the first iteration and that the primary supporting factor is the support of a change champion in the organisation. Based on interviews we have also developed models of ALURE implementation, which show how each implementation was organised. These models demonstrate the generalisability of the ALURE model to various fields of study and institutions and will be of benefit to anyone who is contemplating ALURE implementation

Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function

We evaluate the one loop determinant of matter multiplet fields of N=4 supergravity in the near horizon geometry of quarter BPS black holes, and use it to calculate logarithmic corrections to the entropy of these black holes using the quantum entropy function formalism. We show that even though individual fields give non-vanishing logarithmic contribution to the entropy, the net contribution from all the fields in the matter multiplet vanishes. Thus logarithmic corrections to the entropy of quarter BPS black holes, if present, must be independent of the number of matter multiplet fields in the theory. This is consistent with the microscopic results. During our analysis we also determine the complete spectrum of small fluctuations of matter multiplet fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde

Quantum Fields and Extended Objects in Space-Times with Constant Curvature Spatial Section

The heat-kernel expansion and $\zeta$-regularization techniques for quantum field theory and extended objects on curved space-times are reviewed. In particular, ultrastatic space-times with spatial section consisting in manifold with constant curvature are discussed in detail. Several mathematical results, relevant to physical applications are presented, including exact solutions of the heat-kernel equation, a simple exposition of hyperbolic geometry and an elementary derivation of the Selberg trace formula. With regards to the physical applications, the vacuum energy for scalar fields, the one-loop renormalization of a self-interacting scalar field theory on a hyperbolic space-time, with a discussion on the topological symmetry breaking, the finite temperature effects and the Bose-Einstein condensation, are considered. Some attempts to generalize the results to extended objects are also presented, including some remarks on path integral quantization, asymptotic properties of extended objects and a novel representation for the one-loop (super)string free energy.Comment: Latex file, 122 page

Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection

Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4+ T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4+ T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4+ T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4+ T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies