Limited impact on glucose homeostasis of leptin receptor deletion from insulin- or proglucagon-expressing cells

Aims/hypothesis The adipose tissue-derived hormone leptin plays an important role in the maintenance of body weight and glucose homeostasis. Leptin mediates its effects by interaction with leptin receptors (LepRb), which are highly expressed in the hypothalamus and other brain centres, and at lower levels in the periphery. Previous studies have used relatively promiscuous or inefficient Cre deleter strains, respectively, to explore the roles of LepR in pancreatic β and α cells. Here, we use two newly-developed Cre lines to explore the role of leptin signalling in insulin and proglucagon-expressing cells. Methods Leptin receptor expression was measured in isolated mouse islets and highly-purified islet cells by RNASeq and quantitative RT-PCR. Mice lacking leptin signalling in pancreatic β, or in α and other proglucagon-expressing cells, were generated using Ins1Cre- or iGluCre-mediated recombination respectively of flox'd leptin receptor alleles. In vivo glucose homeostasis, changes in body weight, pancreatic histology and hormone secretion from isolated islets were assessed using standard techniques. Results Leptin receptor mRNA levels were at or below the level of detection in wild-type adult mouse isolated islets and purified cells, and leptin signalling to Stat3 phosphorylation was undetectable. Whereas male mice further deleted for leptin receptors in β cells exhibited no abnormalities in glucose tolerance up to 16 weeks of age, females transiently displayed improved glucose tolerance at 8 weeks (11.2 ± 3.2% decrease in area under curve; p < 0.05), and improved (39.0 ± 13.0%, P < 0.05) glucose-stimulated insulin secretion in vitro. No differences were seen between genotypes in body weight, fasting glucose or β/α cell ratio. Deletion of LepR from α-cells, a minority of β cells, and a subset of proglucagon-expressing cells in the brain, exerted no effects on body weight, glucose or insulin tolerance, nor on pancreatic hormone secretion assessed in vivo and in vitro. Conclusions/interpretation The use here of a highly selective Cre recombinase indicates that leptin signalling plays a relatively minor, age- and sex-dependent role in the control of β cell function in the mouse. No in vivo role for leptin receptors on α cells, nor in other proglucagon-expressing cells, was detected in this study

Health economic assessment tools (HEAT) for walking and for cycling

Physical inactivity is a significant public health problem in most regions of the world, which is unlikely to be solved by classical health promotion approaches alone. The promotion of active transport (cycling and walking) for everyday physical activity is a win-win approach; it not only promotes health but can also lead to positive environmental effects, especially if cycling and walking replace short car trips. Cycling and walking can also be more readily integrated into people’s busy schedules than, for example, leisure-time exercise. These forms of physical activity are also more practicable for groups of the population for which sport is either not feasible because of physical limitations or is not an accessible leisure activity for economic, social or cultural reasons. There is a large potential for active travel in European urban transport, as many trips are short and would be amenable to being undertaken on foot or by bicycle. This, however, requires effective partnerships with the transport and urban planning sectors, whose policies are key driving forces in providing appropriate conditions for such behavioural changes to take place. This has been recognized by a number of international policy frameworks, such as the Action Plan for implementation of the European Strategy for the Prevention and Control of Noncommunicable Diseases 2012–2016, adopted by the WHO Regional Committee for Europe (1). The strategy identifies the promotion of active mobility as one of the supporting interventions endorsed by WHO Member States to address this highpriority topic in the European Region, as do other international policy frameworks such as the Toronto Charter for Physical Activity launched in May 2010 as a global call for action (2)

On narrowing coated conductor film: emergence of granularity-induced field hysteresis of transport critical current

Critical current density Jc in polycrystalline or granular superconducting material is known to be hysteretic with applied field H due to the focusing of field within the boundary between adjacent grains. This is of concern in the so-called coated conductors wherein superconducting film is grown on a granular, but textured surface of a metal substrate. While previous work has mainly been on Jc determined using induced or magnetization currents, the present work utilizes transport current via an applied potential in strip geometry. It is observed that the effect is not as pronounced using transport current, probably due to a large difference in criterion voltage between the two types of measurements. However, when the films are narrowed by patterning into 200-, 100-, or 80-micron, the hysteresis is clearly seen, because of the forcing of percolation across higher-angle grain boundaries. This effect is compared for films grown on ion-beam-assisted-deposited (IBAD) YSZ substrate and those grown on rolling-assisted-biaxially-textures substrates (RABiTS) which have grains that are about ten times larger. The hysteresis is more pronounced for the latter, which is more likely to have a weak grain boundary spanning the width of the microbridge. This is also of concern to applications in which coated conductors will be striated in order to reduce of AC losses.Comment: text-only: 10 pages, plus 5 figures on 5 page

EQUIPT: protocol of a comparative effectiveness research study evaluating cross-context transferability of economic evidence on tobacco control

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.This article has been made available through the Brunel Open Access Publishing Fund.Tobacco smoking claims 700 000 lives every year in Europe and the cost of tobacco smoking in the EU is estimated between €98 and €130 billion annually; direct medical care costs and indirect costs such as workday losses each represent half of this amount. Policymakers all across Europe are in need of bespoke information on the economic and wider returns of investing in evidence-based tobacco control, including smoking cessation agendas. EQUIPT is designed to test the transferability of one such economic evidence base-the English Tobacco Return on Investment (ROI) tool-to other EU member states

Diverse physical growth trajectories in institutionalized portuguese children below age 3: relation to child, family, and institutional factors

The authors would like to thank the students involved in the data collection and coding, and especially the children, caregivers, and other institutional staff who participated in the study. Funding from Fundação para a Ciência e Tecnologia.Objective: To identify and analyze diverse longitudinal trajectories of physical growth of institutionalized children and their relation to child, family, and institutional factors. Methods: 49 institutionalized children were studied for 9 months after admission. Weight, height, and head circumference were measured on 4 occasions, beginning at admission. Data were analyzed using latent class analysis, yielding diverse patterns of growth for each feature, and relations with child characteristics, early family risk factors, and institutional relational care were investigated. Results: For each growth feature, 4 classes emerged: ‘‘Persistently Low,’’ ‘‘Improving,’’ ‘‘Deteriorating,’’ and ‘‘Persistently High.’’ Younger age at admission was a risk factor for impaired physical growth across all domains. Physical characteristics at birth were associated with trajectories across all domains. Lower prenatal risk and better institutional relational care were associated with Improving weight over time. Conclusions: Discussion highlights the role of children’s physical features at birth, prenatal risk, and caregiver’s cooperation with the child in explaining differential trajectories.This research was supported in part by grant 13/06 from Fundação BIAL and by grant PTDC/PSI-PCL/101506/2008 from Fundação para a Ciência e Tecnologia

Pathways to economic well-being among teenage mothers in Great Britain

The present study examines pathways to independence from social welfare among 738 teenage mothers, participants of the 1970 British Cohort Study, who were followed up at age 30 years. Using a longitudinal design, a pathway model is tested, examining linkages between family social background, cognitive ability, school motivation, and individual investments in education, as well as work- and family-related roles. The most important factors associated with financial independence by age 30 are continued attachment to the labor market as well as a stable relationship with a partner (not necessarily the father of the child). Pathways to financial independence, in turn, are predicted through own cognitive resources, school motivation, and family cohesion. Implications of findings for policy making are discussed.© 2010 Hogrefe Publishing

The Blind Psychological Scientists and the Elephant: Reply to Sherlock and Zietsch

The Commentary by Sherlock and Zietsch (2018) raises important questions about how the science of human psychological development moves forward as researchers make dramatic strides in understanding the role of genetics. In this response, we return to these larger questions, but we begin by addressing Sherlock and Zietsch’s specific argument that “genetic contributions should almost always be considered when dealing with associations between parents’ behavior and their children’s behavior” (p. 156). In our 60-year study of the association between warmth of the childhood family environment and late-life security of attachment (Waldinger & Schulz, 2016), we did not mention the potential influence of genetic factors, and we regret this omission. Moreover, we acknowledge that in some places in the article, we used causal language that was not justified by the design of the study. Although we explicitly stated that the association between warmth of the childhood family environment and late-life security of attachment is correlational and not causal, we went on to interpret these findings as indications of support for the influence of childhood environment on well-being in adulthood. Although this is a plausible interpretation, Sherlock and Zietsch are justified in arguing that genetic influences could contribute to this link and that our article should have noted this. The editorial review process encourages investigators to highlight the implications of their work, and in our enthusiasm to convey the importance of an association that spans six decades, we did not adequately address possible alternative explanations for this association. Waldinger, R. J., & Schulz, M. S. (2016). The long reach of nurturing family environments: links with midlife emotion-regulatory styles and late-life security in intimate relationships. Psychological Science. 27.11. http://doi.org/10.1177/095679761666155

A new polymorphic material? Structural degeneracy of ZrMn_2

Based on density functional calculations, we propose that ZrMn_2 is a polymorphic material. We predict that at low temperatures the cubic C15, and the hexagonal C14 and C36 structures of the Laves phase compound ZrMn_2 are nearly equally stable within 0.3 kJmol^{-1} or 30 K. This degeneracy occurs when the Mn atoms magnetize spontaneously in a ferromagnetic arrangement forming the states of lowest energy. From the temperature dependent free energies at T approx 160K we predict a transition from the most stable C15 to the C14 structure, which is the experimentally observed structure at elevated temperatures.Comment: 4 pages, 3 figure

Microscopic Polarization in Bilayer Graphene

Bilayer graphene has drawn significant attention due to the opening of a band gap in its low energy electronic spectrum, which offers a promising route to electronic applications. The gap can be either tunable through an external electric field or spontaneously formed through an interaction-induced symmetry breaking. Our scanning tunneling measurements reveal the microscopic nature of the bilayer gap to be very different from what is observed in previous macroscopic measurements or expected from current theoretical models. The potential difference between the layers, which is proportional to charge imbalance and determines the gap value, shows strong dependence on the disorder potential, varying spatially in both magnitude and sign on a microscopic level. Furthermore, the gap does not vanish at small charge densities. Additional interaction-induced effects are observed in a magnetic field with the opening of a subgap when the zero orbital Landau level is placed at the Fermi energy