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

Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland

The melanocortin-2-receptor (MC2R)/MC2R accessory protein (MRAP) complex is critical to the production of glucocorticoids from the adrenal cortex. Inactivating mutations in either MC2R or MRAP result in the clinical condition familial glucocorticoid deficiency. The localisation of MC2R together with MRAP within the adrenal gland has not previously been reported. Furthermore, MRAP2, a paralogue of MRAP, has been shown in vitro to have a similar function to MRAP, facilitating MC2R trafficking and responsiveness to ACTH. Despite similar MC2R accessory functions, in vivo, patients with inactivating mutations of MRAP fail to be rescued by a functioning MRAP2 gene, suggesting differences in adrenal expression, localisation and/or function between the two MRAPs. In this study on the rat adrenal gland, we demonstrate that while MRAP and MC2R are highly expressed in the zona fasciculata, MRAP2 is expressed throughout the adrenal cortex in low quantities. In the developing adrenal gland, both MRAP and MRAP2 are equally well expressed. The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. Interestingly, expression of MC2R and MRAP in the undifferentiated zone would support the notion that ACTH may play an important role in adrenal cell differentiation and maintenance

Accuracy of automated blood pressure measurements in the presence of atrial fibrillation: systematic review and meta-analysis

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordAtrial fibrillation (AF) affects ~3% of the general population and is twice as common with hypertension. Validation protocols for automated sphygmomanometers exclude people with AF, raising concerns over accuracy of hypertension diagnosis or management, using out-of-office blood pressure (BP) monitoring, in the presence of AF. Some devices include algorithms to detect AF; a feature open to misinterpretation as offering accurate BP measurement with AF. We undertook this review to explore accuracy of automated devices, with or without AF detection, for measuring BP. We searched Medline and Embase to October 2018 for studies comparing automated BP measurement devices to a standard mercury sphygmomanometer contemporaneously. Data were extracted by two reviewers. Mean BP differences between devices and mercury were calculated, where not reported and compared; meta-analyses were undertaken where possible. We included 13 studies reporting 14 devices. Mean systolic and diastolic BP differences from mercury ranged from −3.1 to + 6.1/−4.6 to +9.0 mmHg. Considerable heterogeneity existed between devices (I 2 : 80 to 90%). Devices with AF detection algorithms appeared no more accurate for BP measurement with AF than other devices. A previous review concluded that oscillometric devices are accurate for systolic but not diastolic BP measurement in AF. The present findings do not support that conclusion. Due to heterogeneity between devices, they should be evaluated on individual performance. We found no evidence that devices with AF detection measure BP more accurately in AF than other devices. More home or ambulatory automated BP monitors require validation in populations with AF.National Institute for Health Research (NIHR

Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients

Tacotron: Towards End-to-End Speech Synthesis

A text-to-speech synthesis system typically consists of multiple stages, such as a text analysis frontend, an acoustic model and an audio synthesis module. Building these components often requires extensive domain expertise and may contain brittle design choices. In this paper, we present Tacotron, an end-to-end generative text-to-speech model that synthesizes speech directly from characters. Given pairs, the model can be trained completely from scratch with random initialization. We present several key techniques to make the sequence-to-sequence framework perform well for this challenging task. Tacotron achieves a 3.82 subjective 5-scale mean opinion score on US English, outperforming a production parametric system in terms of naturalness. In addition, since Tacotron generates speech at the frame level, it's substantially faster than sample-level autoregressive methods.Comment: Submitted to Interspeech 2017. v2 changed paper title to be consistent with our conference submission (no content change other than typo fixes

So near and yet so far: harmonic radar reveals reduced homing ability of Nosema infected honeybees.

© 2014 Wolf et al. 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.Citation: Wolf S, McMahon DP, Lim KS, Pull CD, Clark SJ, et al. (2014) So Near and Yet So Far: Harmonic Radar Reveals Reduced Homing Ability of Nosema Infected Honeybees. PLoS ONE 9(8): e103989. doi:10.1371/journal.pone.0103989Pathogens may gain a fitness advantage through manipulation of the behaviour of their hosts. Likewise, host behavioural changes can be a defence mechanism, counteracting the impact of pathogens on host fitness. We apply harmonic radar technology to characterize the impact of an emerging pathogen--Nosema ceranae (Microsporidia)--on honeybee (Apis mellifera) flight and orientation performance in the field. Honeybees are the most important commercial pollinators. Emerging diseases have been proposed to play a prominent role in colony decline, partly through sub-lethal behavioural manipulation of their hosts. We found that homing success was significantly reduced in diseased (65.8%) versus healthy foragers (92.5%). Although lost bees had significantly reduced continuous flight times and prolonged resting times, other flight characteristics and navigational abilities showed no significant difference between infected and non-infected bees. Our results suggest that infected bees express normal flight characteristics but are constrained in their homing ability, potentially compromising the colony by reducing its resource inputs, but also counteracting the intra-colony spread of infection. We provide the first high-resolution analysis of sub-lethal effects of an emerging disease on insect flight behaviour. The potential causes and the implications for both host and parasite are discussed.Biotechnology and Biological Sciences Research Council (BBSRC)Department for Environment Food & Rural Affairs (DEFRA)Natural Environment Research Council (NERC)The Scottish GovernmentWellcome Trus

Micro-beam Laue alignment of multi-reflection Bragg coherent diffraction imaging measurements

Multi-reflection Bragg coherent diffraction imaging has the potential to allow three-dimensional (3D) resolved measurements of the full lattice strain tensor in specific micro-crystals. Until now such measurements were hampered by the need for laborious, time-intensive alignment procedures. Here a different approach is demonstrated, using micro-beam Laue X-ray diffraction to first determine the lattice orientation of the micro-crystal. This information is then used to rapidly align coherent diffraction measurements of three or more reflections from the crystal. Based on these, 3D strain and stress fields in the crystal are successfully determined. This approach is demonstrated on a focused ion beam milled micro-crystal from which six reflections could be measured. Since information from more than three independent reflections is available, the reliability of the phases retrieved from the coherent diffraction data can be assessed. Our results show that rapid, reliable 3D coherent diffraction measurements of the full lattice strain tensor in specific micro-crystals are now feasible and can be successfully carried out even in heavily distorted samples

FlaME: Flash Molecular Editor - a 2D structure input tool for the web

<p>Abstract</p> <p>Background</p> <p>So far, there have been no Flash-based web tools available for chemical structure input. The authors herein present a feasibility study, aiming at the development of a compact and easy-to-use 2D structure editor, using Adobe's Flash technology and its programming language, ActionScript. As a reference model application from the Java world, we selected the Java Molecular Editor (JME). In this feasibility study, we made an attempt to realize a subset of JME's functionality in the Flash Molecular Editor (FlaME) utility. These basic capabilities are: structure input, editing and depiction of single molecules, data import and export in molfile format.</p> <p>Implementation</p> <p>The result of molecular diagram sketching in FlaME is accessible in V2000 molfile format. By integrating the molecular editor into a web page, its communication with the HTML elements on this page is established using the two JavaScript functions, <it>getMol() </it>and <it>setMol()</it>. In addition, structures can be copied to the <it>system clipboard</it>.</p> <p>Conclusion</p> <p>A first attempt was made to create a compact single-file application for 2D molecular structure input/editing on the web, based on Flash technology. With the application examples presented in this article, it could be demonstrated that the Flash methods are principally well-suited to provide the requisite communication between the Flash object (application) and the HTML elements on a web page, using JavaScript functions.</p