Inhibition of food intake in obese subjects by peptide YY3-36

Background: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.Methods: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.Results: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r=-0.84, P<0.001).Conclusions: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity

A method for constrained optimisation of the design of a scanning helium microscope.

We describe a method for obtaining the optimal design of a normal incidence Scanning Helium Microscope (SHeM). Scanning helium microscopy is a recently developed technique that uses low energy neutral helium atoms as a probe to image the surface of a sample without causing damage. After estimating the variation of source brightness with nozzle size and pressure, we perform a constrained optimisation to determine the optimal geometry of the instrument (i.e. the geometry that maximises intensity) for a given target resolution. For an instrument using a pinhole to form the helium microprobe, the source and atom optics are separable and Lagrange multipliers are used to obtain an analytic expression for the optimal parameters. For an instrument using a zone plate as the focal element, the whole optical system must be considered and a numerical approach has been applied. Unlike previous numerical methods for optimisation, our approach provides insight into the effect and significance of each instrumental parameter, enabling an intuitive understanding of effect of the SHeM geometry. We show that for an instrument with a working distance of 1 mm, a zone plate with a minimum feature size of 25 nm becomes the advantageous focussing element if the desired beam standard deviation is below about 300 nm.The work was supported by EPSRC grant EP/R008272/1. M.B. acknowledges an EPSRC studentship and a Leathersellers Graduate scholarship

The effect of bacterial growth phase and culture concentration on U(VI) removal from aqueous solution

Bacteria play a key role in controlling the mobility of contaminants, such as uranium (U), in the environment. Uranium could be sourced from disposed radioactive waste, derived either from surface disposal trenches for Low Level Waste (LLW) that, because of the waste type and disposal concept, would typically present acidic conditions or from the geological disposal of LLW or Intermediate Level Waste (ILW) that, because of the waste type and the disposal concept, would typically present alkaline conditions. In disposed radioactive waste, there could be variable amounts of cellulosic material. Bacterial cells may be living in a range of different growth phases, depending on the growth conditions and nutrients available at the time any waste-derived U migrated to the cells. A key knowledge gap to date has been the lack of a mechanistic understanding of how bacterial growth phases (exponential, stationary, and death phase) affect the ability of bacteria to remove U(VI) from solution. To address this, we first characterised the cells using potentiometric titrations to detect any differences in proton binding to proton active sites on Pseudomonas putida cells at each growth phase under aerobic conditions, or under anaerobic conditions favourable to U(IV) reoxidation. We then conducted batch U(VI) removal experiments with bacteria at each phase suspended in 1 and 10 ppm U aqueous solutions with the pH adjusted from 2 to 12 as well as with culture concentrations from 0.01 to 10 g/L, to identify the minimal concentration of bacteria in solution necessary to affect U removal. We found that, in death phase, P. putida cells exhibited double the concentration of proton active sites than bacteria grown to exponential and stationary phase. However, we did not see a difference in the extent of U(VI) removal, from a 10 ppm U solution, between the different growth phases as a function of pH (2 to 12). Culture concentration affected U removal between pH 2–8, where U removal decreased with a decreasing concentration of cells in solution. When the pH was 10–12, ≤55% of U precipitated abiotically. The presence of bacteria in solution (0.01–10 g/L), regardless of growth phase, increased the precipitation of U from ≤55% up to 70–90%, accumulating inside the cells and on the cell walls as ~0.2 μm uranyl phosphate precipitates. These precipitates were also found at low pH with the exception of cells at exponential growth phase. This study demonstrates that growth phase affects the proton-active site concentration but not the extent of U bound to P. putida cells and that growth phase dictates the form of U removed from solution. Since the pH of trench-disposed LLW is controlled by the degradation of cellulosic waste, leading to acidic conditions (pH 4–6), bacterial concentrations would be expected to highly affect the extent of U removed from solution. The cement in grouted ILW and LLW, for geologic disposal, will allow for the development of extremely high pH values in solution (pH 9–13), where even the smallest concentrations of bacteria were able to significantly increase the removal of U from solution under aerobic conditions, or under anaerobic conditions favourable to U(IV) reoxidation

Genotype reconstruction of paternity in European lobsters (Homarus gammarus)

This is the author accepted manuscript. The final version is available on open access from Public Library of Science via the DOI in this recordData Availability: Microsatellite genotypes of 312 individuals (13 spatial samples of 24 individuals), used in the calculation of regional allele frequencies, microsatellite characterisation, and tests of HWE, linkage and null alleles, are available on the Dryad Digital Repository at http://dx.doi.org/10.5061/dryad.v176mDecapod crustaceans exhibit considerable variation in fertilisation strategies, ranging from pervasive single paternity to the near-ubiquitous presence of multiple paternity, and such knowledge of mating systems and behaviour are required for the informed management of commercially-exploited marine fisheries. We used genetic markers to assess the paternity of individual broods in the European lobster, Homarus gammarus, a species for which paternity structure is unknown. Using 13 multiplexed microsatellite loci, three of which are newly described in this study, we genotyped 10 eggs from each of 34 females collected from an Atlantic peninsula in the south-western United Kingdom. Single reconstructed paternal genotypes explained all observed progeny genotypes in each of the 34 egg clutches, and each clutch was fertilised by a different male. Simulations indicated that the probability of detecting multiple paternity was in excess of 95% if secondary sires account for at least a quarter of the brood, and in excess of 99% where additional sire success was approximately equal. Our results show that multiple paternal fertilisations are either absent, unusual, or highly skewed in favour of a single male among H. gammarus in this area. Potential mechanisms upholding single paternal fertilisation are discussed, along with the prospective utility of parentage assignments in evaluations of hatchery stocking and other fishery conservation approaches in light of this finding.European Social FundFisheries Charitable Trust of the Fishmongers' Company, U

Impaired insulin profiles following a single night of sleep restriction: the impact of acute sprint interval exercise

Experimental sleep restriction (SR) has demonstrated reduced insulin sensitivity in healthy individuals. Exercise is well-known to be beneficial for metabolic health. A single bout of exercise has the capacity to increase insulin sensitivity for up to 2 days. Therefore, the current study aimed to determine if sprint interval exercise could attenuate the impairment in insulin sensitivity after one night of SR in healthy males. Nineteen males were recruited for this randomized crossover study which consisted of four conditions—control, SR, control plus exercise, and sleep restriction plus exercise. Time in bed was 8 hr (2300–0700) in the control conditions and 4 hr (0300–0700) in the SR conditions. Conditions were separated by a 1-week entraining period. Participants slept at home, and compliance was assessed using wrist actigraphy. Following the night of experimental sleep, participants either conducted sprint interval exercise or rested for the equivalent duration. An oral glucose tolerance test was then conducted. Blood samples were obtained at regular intervals for measurement of glucose and insulin. Insulin concentrations were higher in SR than control (p = .022). Late-phase insulin area under the curve was significantly lower in sleep restriction plus exercise than SR (862 ± 589 and 1,267 ± 558; p = .004). Glucose area under the curve was not different between conditions (p = .207). These findings suggest that exercise improves the late postprandial response following a single night of SR

Energy Dissipation during Diffusion at Metal Surfaces: Disentangling the Role of Phonons versus Electron-Hole Pairs

Helium spin echo experiments combined with $\textit{ab initio}$ based Langevin molecular dynamics simulations are used to quantify the adsorbate-substrate coupling during the thermal diffusion of Na atoms on Cu(111). An analysis of trajectories within the local density friction approximation allows the contribution from electron-hole pair excitations to be separated from the total energy dissipation. Despite the minimal electronic friction coefficient of Na and the relatively small mass mismatch to Cu promoting efficient phononic dissipation, about (20±5)% of the total energy loss is attributable to electronic friction. The results suggest a significant role of electronic nonadiabaticity in the rapid thermalization generally relied upon in adiabatic diffusion theories.S. P. R. acknowledges the support of the Technische Universität München—Institute for Advanced Study, funded by the German Excellence Initiative and the European Union Seventh Framework Programme under Grant Agreement No. 291763

PIGLE — Particles Interacting in Generalized Langevin Equation simulator

We present a package using Simulink and MATLAB to perform molecular dynamics simulations of interacting particles obeying a Generalized Langevin Equation. The package, which accounts for three spatial dimensions and rigid-body like rotation, is tuned to explore surface diffusion of co-adsorbed species. The physical parameters are species specific, and include userdefined colored noise spectra and memory friction kernels acting independently on translational and rotational degrees of freedom. We benchmark the simulations using established analytical results for dynamical correlation functions, and we use the package to numerically verify novel analytical results concerning dissipative rotational motion and mutli-exponential friction kernels. The package provides a straight-forward way to expand the modeling of ultra-fast surface diffusion problems at the atomic scale.Herchel Smith Fund, Blavatnik Foundatio

Age-related changes to the neural correlates of working memory which emerge after midlife

Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance. &copy; 2014 Macpherson, White, Ellis, Stough, Camfield, Silberstein and Pipingas

An Exploration of the Patient Lived Experience of Remission and Relapse of Type 2 Diabetes Following Bariatric Surgery

BACKGROUND: Bariatric surgery is the most effective treatment for patients with obesity and type 2 diabetes (T2DM), inducing profound metabolic changes associated with improvements in glycaemic control. In spite of the recognition of the physiological changes associated with bariatric surgery, what remains underappreciated is the patient experience of surgery to treat T2DM. OBJECTIVES: This study explored the patient experience with regard to motivations, expectations and outcomes, including remission and relapse of diabetes. METHODS: An in-depth qualitative approach was adopted, encompassing semi-structured interviews with patients (n=17) living with obesity and T2DM both pre- and postsurgery. Interpretive thematic analysis identified emergent themes using a grounded approach. RESULTS: Analysis revealed a number of themes throughout the interviews which included motivations and perceived benefits of surgery, obesity stigma and its impact on self-worth as well as perceptions of remission or relapse and the implications for sense of control. CONCLUSIONS: The motivation for undergoing bariatric surgery was driven by health concerns, namely T2DM and the desire to reduce the risk of developing diabetes-related complications. Patients highlighted social and self-stigmatisation associated with obesity and T2DM, leading to feelings of shame and an inability to seek support from family or healthcare professionals. Stigmatisation created a sense of failure and feeling of guilt for having T2DM. As a result, patients felt responsible for maintaining disease remission postoperatively and regarded the need for medication as a sign of treatment failure