Wing Defects in Drosophila xenicid Mutant Clones Are Caused by C-Terminal Deletion of Additional Sex Combs (Asx)

Background: The coordinated action of genes that control patterning, cell fate determination, cell size, and cell adhesion is required for proper wing formation in Drosophila. Defects in any of these basic processes can lead to wing aberrations, including blisters. The xenicid mutation was originally identified in a screen designed to uncover regulators of adhesion between wing surfaces [1]. Principal Findings: Here, we demonstrate that expression of the bPS integrin or the patterning protein Engrailed are not affected in developing wing imaginal discs in xenicid mutants. Instead, expression of the homeotic protein Ultrabithorax (Ubx) is strongly increased in xenicid mutant cells. Conclusion: Our results suggest that upregulation of Ubx transforms cells from a wing blade fate to a haltere fate, and that the presence of haltere cells within the wing blade is the primary defect leading to the adult wing phenotypes observed

Service delivery interventions to increase uptake of voluntary medical male circumcision for HIV prevention: A systematic review.

BackgroundVoluntary medical male circumcision (VMMC) remains an essential component of combination HIV prevention services, particularly in priority countries in sub-Saharan Africa. As VMMC programs seek to maximize impact and efficiency, and to support World Health Organization guidance, specific uptake-enhancing strategies are critical to identify.MethodsWe systematically reviewed the literature to evaluate the impact of service delivery interventions (e.g., facility layout, service co-location, mobile outreach) on VMMC uptake among adolescent and adult men. For the main effectiveness review, we searched for publications or conference abstracts that measured VMMC uptake or uptake of HIV testing or risk reduction counselling within VMMC services. We synthesized data by coding categories and outcomes. We also reviewed studies assessing acceptability, values/preferences, costs, and feasibility.ResultsFour randomized controlled trials and five observational studies were included in the effectiveness review. Studies took place in South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. They assessed a range of service delivery innovations, including community-, school-, and facility-based interventions. Overall, interventions increased VMMC uptake; some successfully improved uptake among age-specific subpopulations, but urban-rural stratification showed no clear trends. Interventions that increased adult men's uptake included mobile services (compared to static facilities), home-based testing with active referral follow-up, and facility-based HIV testing with enhanced comprehensive sexual education. Six acceptability studies suggested interventions were generally perceived to help men choose to get circumcised. Eleven cost studies suggested interventions create economies-of-scale and efficiencies. Three studies suggested such interventions were feasible, improving facility preparedness, service quality and quantity, and efficiencies.ConclusionsInnovative changes in male-centered VMMC services can improve adult men's and adolescent boys' VMMC uptake. Limited evidence on interventions that enhance access and acceptability show promising results, but evidence gaps persist due to inconsistent intervention definition and delivery, due in part to contextual relevance and limited age disaggregation

Economic compensation interventions to increase uptake of voluntary medical male circumcision for HIV prevention: A systematic review and meta-analysis.

BackgroundEconomic compensation interventions may help support higher voluntary medical male circumcision (VMMC) coverage in priority sub-Saharan African countries. To inform World Health Organization guidelines, we conducted a systematic review of economic compensation interventions to increase VMMC uptake.MethodsEconomic compensation interventions were defined as providing money or in-kind compensation, reimbursement for associated costs (e.g. travel, lost wages), or lottery entry. We searched five electronic databases and four scientific conferences for studies examining the impact of such interventions on VMMC uptake, HIV testing and safer-sex/risk-reduction counseling uptake within VMMC, community expectations about compensation, and potential coercion. We screened citations, extracted data, and assessed risk of bias in duplicate. We conducted random-effects meta-analysis. We also reviewed studies examining acceptability, values/preferences, costs, and feasibility.ResultsOf 2484 citations identified, five randomized controlled trials (RCTs) and three non-randomized controlled trials met our eligibility criteria. Studies took place in Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Meta-analysis of four RCTs showed significant impact of any economic compensation on VMMC uptake (relative risk: 5.23, 95% CI: 3.13 to 8.76). RCTs of food/transport vouchers and conditional cash transfers generally showed increases in VMMC uptake, but lotteries, subsidized VMMC, and receiving a gift appeared somewhat less effective. Three non-randomized trials showed mixed impact. Six additional studies suggested economic compensation interventions were generally acceptable, valued for addressing key barriers, and motivating to men. However, some participants felt they were insufficiently motivating or necessary; one study suggested they might raise community suspicions. One study from South Africa found a program cost of US$91 per additional circumcision and US$450-$1350 per HIV infection averted.ConclusionsEconomic compensation interventions, particularly transport/food vouchers, positively impacted VMMC uptake among adult men and were generally acceptable to potential clients. Carefully selected economic interventions may be a useful targeted strategy to enhance VMMC coverage

Association of Interleukin-6 Signalling with the Muscle Stem Cell Response Following Muscle-Lengthening Contractions in Humans

BACKGROUND: The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6) has been implicated in muscle stem cell (satellite cell)-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satellite cell (SC) response following muscle-lengthening contractions in humans has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: Eight subjects (age 22+/-1 y; 79+/-8 kg) performed 300 maximal unilateral lengthening contractions (3.14 rad.s(-1)) of the knee extensors. Blood and muscle samples were collected before and at 4, 24, 72, and 120 hours post intervention. IL-6, IL-6 receptor, IL-6R(alpha), cyclin D1, suppressor of cytokine signling-3 (SOCS3) mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit. JAK2 and STAT3 phosphorylated and total protein was measured using western blotting techniques. Immunohistochemical analysis of muscle cross-sections was performed for the quantification of SCs (Pax7(+) cells) as well as the expression of phosphorylated STAT3, IL-6, IL-6R(alpha), and PCNA across all time-points. The SC response, as defined by an amplification of Pax7(+) cells, was rapid, increasing by 24 h and peaking 72 h following the intervention. Muscle IL-6 mRNA increased following the intervention, which correlated strongly (R(2) = 0.89, p<0.002) with an increase in serum IL-6 concentration. SC IL-6R(alpha) protein was expressed on the fiber, but was also localized to the SC, and IL-6(+) SC increased rapidly following muscle-lengthening contractions and returned to basal levels by 72 h post-intervention, demonstrating an acute temporal expression of IL-6 with SC. Phosphorylated STAT3 was evident in SCs 4 h after lengthening contraction, and the downstream genes, cyclin D1 and SOCS3 were significantly elevated 24 hours after the intervention. CONCLUSIONS/SIGNIFICANCE: The increased expression of STAT3 responsive genes and expression of IL-6 within SCs demonstrate that IL-6/STAT3 signaling occurred in SCs, correlating with an increase in SC proliferation, evidenced by increased Pax7(+)/PCNA(+) cell number in the early stages of the time-course. Collectively, these data illustrate that IL-6 is an important signaling molecule associated with the SC response to acute muscle-lengthening contractions in humans

Electronic structure evolution in dilute carbide Ge1-xCx alloys and implications for device applications

We present a theoretical analysis of electronic structure evolution in the highly-mismatched dilute carbide group-IV alloy Ge1−xCx. For ordered alloy supercells, we demonstrate that C incorporation strongly perturbs the conduction band (CB) structure by driving the hybridization of A1-symmetric linear combinations of Ge states lying close in energy to the CB edge. This leads, in the ultradilute limit, to the alloy CB edge being formed primarily of an A1-symmetric linear combination of the L-point CB edge states of the Ge host matrix semiconductor. Our calculations describe the emergence of a “quasidirect” alloy bandgap, which retains a significant admixture of indirect Ge L-point CB edge character. We then analyze the evolution of the electronic structure of realistic (large, disordered) Ge1−xCx alloy supercells for C compositions up to x=2%. We show that short-range alloy disorder introduces a distribution of localized states at energies below the Ge CB edge, with these states acquiring minimal direct (Γ) character. Our calculations demonstrate strong intrinsic inhomogeneous energy broadening of the CB edge Bloch character, driven by hybridization between Ge host matrix and C-related localized states. The trends identified by our calculations are markedly different to those expected based on a recently proposed interpretation of the CB structure based on the band anticrossing model. The implications of our findings for device applications are discussed

A guide to naming human non-coding RNA genes.

Research on non-coding RNA (ncRNA) is a rapidly expanding field. Providing an official gene symbol and name to ncRNA genes brings order to otherwise potential chaos as it allows unambiguous communication about each gene. The HUGO Gene Nomenclature Committee (HGNC, www.genenames.org) is the only group with the authority to approve symbols for human genes. The HGNC works with specialist advisors for different classes of ncRNA to ensure that ncRNA nomenclature is accurate and informative, where possible. Here, we review each major class of ncRNA that is currently annotated in the human genome and describe how each class is assigned a standardised nomenclature

Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year. Methods and Findings In this study, 573 women were randomised to either the intervention (n = 284) or usual care (n = 289). At baseline, 10% had impaired glucose tolerance and 2% impaired fasting glucose. The diabetes prevention intervention comprised one individual session, five group sessions, and two telephone sessions. Primary outcomes were changes in diabetes risk factors (weight, waist circumference, and fasting blood glucose), and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors. The mean changes (intention-to-treat [ITT] analysis) over 12 mo were as follows: −0.23 kg body weight in intervention group (95% CI −0.89, 0.43) compared with +0.72 kg in usual care group (95% CI 0.09, 1.35) (change difference −0.95 kg, 95% CI −1.87, −0.04; group by treatment interaction p = 0.04); −2.24 cm waist measurement in intervention group (95% CI −3.01, −1.42) compared with −1.74 cm in usual care group (95% CI −2.52, −0.96) (change difference −0.50 cm, 95% CI −1.63, 0.63; group by treatment interaction p = 0.389); and +0.18 mmol/l fasting blood glucose in intervention group (95% CI 0.11, 0.24) compared with +0.22 mmol/l in usual care group (95% CI 0.16, 0.29) (change difference −0.05 mmol/l, 95% CI −0.14, 0.05; group by treatment interaction p = 0.331). Only 10% of women attended all sessions, 53% attended one individual and at least one group session, and 34% attended no sessions. Loss to follow-up was 27% and 21% for the intervention and control groups, respectively, primarily due to subsequent pregnancies. Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline. Conclusions Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk, the level of engagement during the first postnatal year was low. Further research is needed to improve engagement, including participant involvement in study design; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN1261000033806

Lung-Specific Extracellular Superoxide Dismutase Improves Cognition of Adult Mice Exposed to Neonatal Hyperoxia

Lung and brain development is often altered in infants born preterm and exposed to excess oxygen, and this can lead to impaired lung function and neurocognitive abilities later in life. Oxygen-derived reactive oxygen species and the ensuing inflammatory response are believed to be an underlying cause of disease because over-expression of some anti-oxidant enzymes is protective in animal models. For example, neurodevelopment is preserved in mice that ubiquitously express human extracellular superoxide dismutase (EC-SOD) under control of an actin promoter. Similarly, oxygen-dependent changes in lung development are attenuated in transgenic SftpcEC−SOD mice that over-express EC-SOD in pulmonary alveolar epithelial type II cells. But whether anti-oxidants targeted to the lung provide protection to other organs, such as the brain is not known. Here, we use transgenic SftpcEC−SOD mice to investigate whether lung-specific expression of EC-SOD also preserves neurodevelopment following exposure to neonatal hyperoxia. Wild type and SftpcEC−SOD transgenic mice were exposed to room air or 100% oxygen between postnatal days 0–4. At 8 weeks of age, we investigated neurocognitive function as defined by novel object recognition, pathologic changes in hippocampal neurons, and microglial cell activation. Neonatal hyperoxia impaired novel object recognition memory in adult female but not male mice. Behavioral deficits were associated with microglial activation, CA1 neuron nuclear contraction, and fiber sprouting within the hilus of the dentate gyrus (DG). Over-expression of EC-SOD in the lung preserved novel object recognition and reduced the observed changes in neuronal nuclear size and myelin basic protein fiber density. It had no effect on the extent of microglial activation in the hippocampus. These findings demonstrate pulmonary expression of EC-SOD preserves short-term memory in adult female mice exposed to neonatal hyperoxia, thus suggesting anti-oxidants designed to alleviate oxygen-induced lung disease such as in preterm infants may also be neuroprotective