The melanocortin receptors and their accessory proteins.

The five melanocortin receptors (MCRs) named MC1R-MC5R have diverse physiological roles encompassing pigmentation, steroidogenesis, energy homeostasis and feeding behavior as well as exocrine function. Since their identification almost 20 years ago much has been learnt about these receptors. As well as interacting with their endogenous ligands the melanocortin peptides, there is now a growing list of important peptides that can modulate the way these receptors signal, acting as agonists, antagonists, and inverse agonists. The discovery of melanocortin 2 receptor accessory proteins as a novel accessory factor to the MCRs provides further insight into the regulation of these important G protein-coupled receptor

Panoramic 360◦ videos in virtual reality using two lenses and a mobile phone

Cameras generally have a 60◦ field of view of and can capture only a portion of their surroundings. Panoramic cameras are used to capture the entire 360◦ view known as panoramic images. Virtual reality makes use of these panoramic images to provide a more immersive experience compared to seeing images on a 2D screen. Most of the panoramic cameras are expensive. It is important for the camera to be affordable in order for virtual reality to become a part of daily life. This is a comprehensive document about the successful implementation of the cheapest 360◦ video camera, using multiple lenses on a mobile phone. With the advent of technology nearly everyone has a mobile phone. Equipping these mobile phones with the technology to capture panoramic images using multiple lenses will convert them into the most economical panoramic camera

Kinetics of dopamine oxidation by sodium N-bromo-p-toluenesulphonamide in acid medium. A mechanistic approach

The oxidation kinetics of dopamine (DPM) by sodium N-bromo-p-toluenesulphonamide (bromamine-T or BAT) was investigated at 40°C in HClO4 medium. The rate is first order in BAT0, fractional order in DPM0 and inverse fractional in H+. Addition of reaction product, p-toluenesulphonamide, or halide ions and variation of ionic strength of the medium have no significant effect on the rate. The dielectric effect is positive. The solvent isotope effect has been studied in D2O medium. The reaction fails to induce the polymerisation of acrylonitrile. The Michaelis-Menten type of kinetics is observed. Activation parameters for the overall reaction and also for the rate-limiting step were computed. Dopa-o-quinone or 2-(3â²4â²-benzoquinone) ethylamine was identified as the oxidation product of DPM. A mechanism consistent with the observed kinetics is proposed and discussed

Kinetics and mechanism of ruthenium(III) catalyzed oxidation of secondary alcohols by bromamine-​T in hydrochloric acid solutions

The kinetics of oxidn. of 2-​propanol, 2-​butanol, 2-​pentanol, 2-​hexanol, and 2-​heptanol by Na N-​bromo-​p-​toluenesulfonamide (bromamine-​T or BAT) to the corresponding ketones in the presence of HCl and catalyzed by Ru(III) chloride was studied at 30°. The reaction rate shows a first-​order dependence on [BAT] and a fractional-​order each on [alc.]​, [Ru(III)​] and [H+]​. Addn. of the reaction product, p-​toluenesulfonamide, retards the rate. An increase in the dielec. const. of the medium decreases the rate. Variations of ionic strength and halide ion concn. have no effect on the rate. Rate studies in D2O medium show that the solvent isotope effect, k'(H2O)​/k'(D2O)​, is 0.67. Proton inventory studies were carried out using H2O-​D2O mixts. Attempts were made to arrive at a linear free-​energy relation through the Taft treatment and obsd. that the rate consts. do not correlate satisfactorily. An isokinetic relation is obsd. with β = 354K indicating that enthalpy factors control the rate which is also confirmed by the Exner criterion. A mechanism consistent with the obsd. kinetics was proposed and discussed

Influence of rotation and sources of nutrients on soil properties and productivity of finger millet (Eleusinecoracana L. Gaertn.)

A field experiment was conducted at the All India Co-ordinated Research Project for Dryland Agriculture, UAS, GKVK, Bengaluru during kharif 2013-14. The experiment was laid out with 20 treatment combinations with three factors using factorial RBD with two replications comprised of on a permanent manurial trial with 35th crop cycle. Application of FYM at 10 t ha-1 has recorded significantly higher grain yield (1.76 t ha-1), maximum water holding capacity (MWHC) of 43.85 % and dehydrogenase activity (DHA) of 357.60?g TPF g-1 24 h-1 obtained after harvest of the crop as compared to application of maize residues at 5 t ha-1 (1.37 t ha-1, 42.27 % and 193.0?g TPF g-1 24 h-1 respectively) due to improved growth and yield parameters of finger millet. However, finger millet-groundnut rotation has given significantly higher grain yield (1.78 t ha-1), MWHC (43.66 %) and DHA (298.48?g TPF g-1 24 h-1) after harvest of the crop over mono cropping of finger millet (1.34 t ha-1, 42.46% and 252.12?g TPFg-1 24 h-1respectively ). Among different nutrient sources, application of organic matter with 100 % RDF have given significantly higher grain yield (2.74 t ha-1), MWHC (45.86 %) and DHA (431.13?g TPF g-1 24 h-1) after harvest of the crop compared to absolute control (0.28 t ha-1, 41.76 % and 133.67?g TPFg-1 24 h-1 respectively). The 100 % recommended dose of fertilizer + organic matter significantly increased yield attributes because of improved soil physical and chemical properties and increased microbial activity of the soil with continued application of organic matter

Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi-like features

Sim1 haploinsufficiency in mice induces hyperphagic obesity and developmental abnormalities of the brain. In humans, abnormalities in chromosome 6q16, a region that includes SIM1, were reported in obese children with a Prader-Willi–like syndrome; however, SIM1 involvement in obesity has never been conclusively demonstrated. Here, SIM1 was sequenced in 44 children with Prader-Willi–like syndrome features, 198 children with severe early-onset obesity, 568 morbidly obese adults, and 383 controls. We identified 4 rare variants (p.I128T, p.Q152E, p.R581G, and p.T714A) in 4 children with Prader-Willi–like syndrome features (including severe obesity) and 4 other rare variants (p.T46R, p.E62K, p.H323Y, and p.D740H) in 7 morbidly obese adults. By assessing the carriers’ relatives, we found a significant contribution of SIM1 rare variants to intra-family risk for obesity. We then assessed functional effects of the 8 substitutions on SIM1 transcriptional activities in stable cell lines using luciferase gene reporter assays. Three mutations showed strong loss-of-function effects (p.T46R, p.H323Y, and p.T714A) and were associated with high intra-family risk for obesity, while the variants with mild or no effects on SIM1 activity were not associated with obesity within families. Our genetic and functional studies demonstrate a firm link between SIM1 loss of function and severe obesity associated with, or independent of, Prader-Willi–like features.Amélie Bonnefond, Anne Raimondo, Fanny Stutzmann, Maya Ghoussaini, Shwetha Ramachandrappa, David C. Bersten, Emmanuelle Durand, Vincent Vatin, Beverley Balkau, Olivier Lantieri, Violeta Raverdy, François Pattou, Wim Van Hul, Luc Van Gaal, Daniel J. Peet, Jacques Weill, Jennifer L. Miller, Fritz Horber, Anthony P. Goldstone, Daniel J. Driscoll, John B. Bruning, David Meyre, Murray L. Whitelaw and Philippe Frogue

Variation at the Melanocortin 4 Receptor gene and response to weight-loss interventions in the Diabetes Prevention Program

Objective: To assess associations and genotype × treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. Design and Methods Diabetes Prevention Program (DPP) participants (N=3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n=909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment. Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P=0.032) and long-term (2 year; P=0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all Pinteraction <0.05). Conclusion: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions

Advancing the Contour Method to Characterise Residual Stress in Polymer Composites

The manufacturing route for polymer composites inevitably introduces residual stress. It entails cooling from high cure temperature to room temperature accompanied by constrained shrinkage. The constraints arise from the micro-scale contraction between the fibre and matrix, as well as the macro-scale contraction between adjacent plies with varying fibre orientations inducing strain dissimilarities. The resulting residual stresses are directly associated with dimensional stability such as warpage, shape distortion and the structural integrity of composite structures (e.g. matrix cracking, reduced fibre-matrix bondage and delamination toughness). The composite structures may need to be pre-loaded to get the desired assembly tolerances, creating additional internal stresses and reducing overall performance. Therefore, knowledge and accurate characterisation of residual stress is imperative for optimising the design and structural integrity of polymer composites. Analytical and numerical methods have been developed to predict residual stresses in polymer composites, but these procedures are computationally expensive and require cure and temperature dependent physio-chemo-rheological properties. Experimental methods offer an alternative solution for developing a quantitative understanding of the sign, magnitude and distribution of residual stresses. They are essential for validation of predictive methods. However, the characterization of bulk residual stress in polymer composites remains a challenge as there is currently no experimental approach available for this purpose. The present study investigates the viability of using the Contour Method for measuring 2-dimensional residual stress in polymer composites. Traditionally, the method has been solely applied to metallic structures. The challenge to address is to expand its applications to non-metallic structures through identifying suitable methods for cutting the material. In this work, the feasibility of five different cutting techniques such as wire EDM, abrasive waterjet machine, diamond wire machine, milling machine with end mill and slit saw tools for contour analysis is explored. The results of contour cutting on asymmetric and symmetric epoxy Carbon Fibre Reinforced Polymer (CFRP) cross ply laminates are presented and discussed. The created cut surfaces are carefully interrogated using optical microscopy, scanning electron microscopy, and high-resolution surface topological scanning methods. The quality of contour cuts and the corresponding optimal conditions were evaluated based on three surface features criteria, such as cutting artefacts, subsurface damage and surface roughness coefficient. The deformations observed on the cut surface created by the diamond wire method, as a consequence of the relief of residual stress, clearly demonstrate the ply orientations in both asymmetric and symmetric samples. Therefore, among the five cutting techniques evaluated, the cut quality of the diamond wire machine was found to be sufficiently good for measuring deformation resulting from residual stress relaxation. The diamond wire cutting technique is evaluated by means of a thermal mapping device to ensure that the cutting temperature remains below the glass transition temperature, which is determined using Differential Scanning Calorimetry. The measured out of plane displacement data obtained from the optimum cutting process were then processed using the standard approach for contour measurement. The investigation of data analysis parameters along with the provision of guidelines to assist practitioners of the contour method measurement in selecting an appropriate surface measurement density, mask size for smoothing the deformation data, finite element mesh size for contour method data collection and analysis are reviewed. In addition, a correlation has also been discussed between the minimum resolvable residual stress length scale and the size of constituents and surface roughness induced by the diamond wire cutting process. Finally, residual stresses through the thickness of asymmetric and symmetric samples measured by the Contour Method using diamond wire cutting are presented. The results are validated against measurements using the slitting method. In compliment, they are also compared to Classical Laminate Theory based analytical results and thermally simulated residual stress in ABAQUS and the limitations are addressed. The research marks the first instance of implementing the method on epoxy CFRP composites and showcases the capability of the contour method in determining bulk residual stress distribution across the thickness of cross-ply laminates

Rare variants in single-minded 1 (SIM1) are associated with severe obesity

Single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor involved in the development and function of the paraventricular nucleus of the hypothalamus. Obesity has been reported in Sim1 haploinsufficient mice and in a patient with a balanced translocation disrupting SIM1. We sequenced the coding region of SIM1 in 2,100 patients with severe, early onset obesity and in 1,680 controls. Thirteen different heterozygous variants in SIM1 were identified in 28 unrelated severely obese patients. Nine of the 13 variants significantly reduced the ability of SIM1 to activate a SIM1-responsive reporter gene when studied in stably transfected cells coexpressing the heterodimeric partners of SIM1 (ARNT or ARNT2). SIM1 variants with reduced activity cosegregated with obesity in extended family studies with variable penetrance. We studied the phenotype of patients carrying variants that exhibited reduced activity in vitro. Variant carriers exhibited increased ad libitum food intake at a test meal, normal basal metabolic rate, and evidence of autonomic dysfunction. Eleven of the 13 probands had evidence of a neurobehavioral phenotype. The phenotypic similarities between patients with SIM1 deficiency and melanocortin 4 receptor (MC4R) deficiency suggest that some of the effects of SIM1 deficiency on energy homeostasis are mediated by altered melanocortin signaling.Shwetha Ramachandrappa, Anne Raimondo, Anna M.G. Cali, Julia M. Keough, Elana Henning, Sadia Saeed, Amanda Thompson, Sumedha Garg, Elena G. Bochukova, Soren Brage, Victoria Trowse, Eleanor Wheeler, Adrienne E. Sullivan, Mehul Dattani, Peter E. Clayton, Vippan Datta, John B. Bruning, Nick J. Wareham, Stephen O'Rahilly, Daniel J. Peet, Ines Barroso, Murray L. Whielaw and I. Sadaf Farooq