Interactions between view changes and shape changes in picture-picture matching

Four studies presented pictures of different morphs of novel, complex, three-dimensional objects, similar to objects which we must identify in the real world. We investigated how viewpoint changes influence our ability to discriminate between morphs. View changes had a powerful effect on performance in picture-picture matching tasks when similarly shaped morphs had to be discriminated. Shape changes were detected faster and more accurately when morphs were depicted from the same rather than different views. In contrast, view change had no effect when dissimilarly shaped morphs had to be discriminated. This interaction between the effects of view change and shape change was found for both simultaneous stimulus presentation and for sequential presentation with interstimulus intervals of up to 3600ms. The interaction was found following repeated presentations of the stimuli prior to the matching task and following practice at the matching task as well as after no such pre-exposure to the stimuli or to the task. The results demonstrate the importance of view changes relative to other task manipulations in modulating the shape discrimination abilities of the human visual recognition system

An appetite for growth: the role of the hypothalamic–pituitary–growth hormone axis in energy balance

Links between the regulation of growth and energy balance are clear; to fuel growth, there must be consumption of energy. Therefore, it is perhaps intuitive that interactions between the hypothalamic – pituitary – growth hormone axis (growth axis) and pathways that drive metabolic processes exist. Overproduction of growth hormone has been associated with diabetes and metabolic disease for decades and the opposing effects of growth hormone and insulin have been studied since early experiments almost a century ago. The relationship between neuroendocrine axes can be complex and the growth axis is no exception, interacting with energy balance in several organ systems, both in the periphery and centrally in hypothalamic nuclei. Much is known about peripheral interactions between growth axis hormones and processes such as glucose homeostasis and adipogenesis. More is still being learned about the molecular actions of growth axis hormones in adipose and other metabolically active tissues, and recent findings are discussed in this perspective. However, less is known about interactions with central energy balance pathways in the hypothalamus. This perspective aims to summarise what is known about these interactions, taking lessons from human studies and animal genetic and seasonal models, and discusses what this may mean in an evolving landscape of personalised medicine

Endocrine drivers of photoperiod response

YesLife in a seasonally variable environment has evolved to interpret the time of year through day length (photoperiod) which is translated into a neurochemical signal. In mammals, the pars tuberalis is a key site where seasonal time signal (melatonin) interfaces and relays photoperiodic information to the hypothalamus via thyrotropin. Recent work has elucidated a potential circannual clock in ‘calendar cells’ of the pars tuberalis. In the hypothalamus, tanycytes are an integral part of the hypothalamic network. Previous studies show the importance of local synthesis of thyroid hormone and retinoic acid in tanycytes. Recently novel downstream neuroendocrine signals, e.g. VGF, FGF21 and chemerin, were identified to govern seasonally appropriate phenotype. Additionally, the hypothalamic-pituitary-growth axis has been implicated in seasonally bodyweight and torpor regulation. Here, we will focus on the endocrine drivers of photoperiod response and highlight novel downstream effects on bodyweight and growth focusing on recent findings from seasonal rodent studies

Somatostatin agonist pasireotide inhibits exercise stimulated growth in the male Siberian hamster (Phodopus sungorus)

R.Dumbell was supported by a University of Aberdeen PhD studentship and a research visit grant awarded by the British Society of Neuroendocrinology. Further support was provided by the Scottish Government Rural and Environment Science and Analytical Services Division (Barrett and the German Research Foundation (DFG; STE 331/8-1; Steinlechner lab). We are grateful for technical assistance from Dana Wilson at RINH and Siegried Hiliken at UVMH, and thank Dr Claus-Dieter Mayer of Biomathematics & Statistics Scotland for valuable advice on statistical analysis.Peer reviewedPostprin

First Results of Magnetic Field Penetration Measurements of Multilayer SIS Structures

The performance of superconducting RF cavities made of bulk Nb is limited by a breakdown field of Bp ≈200 mT, close to the superheating field for Nb. A potentially promising solution to enhance the breakdown field of the SRF cavities beyond the intrinsic limits of Nb is a multilayer coating suggested in [1]. In the simplest case, such a multilayer may be a superconductor-insulator-superconductor (S-I-S) coating, for example, bulk niobium (S) coated with a thin film of insulator (I) followed by a thin layer of another superconductor (S) which could be e.g. dirty niobium [2]. Here we report the first results of our measurements of field penetration in Nb thin films and Nb-AlN-Nb multilayer samples at 4.2 K using the magnetic field penetration facility designed, built and tested in ASTeC

Modelling the genetic aetiology of complex disease: human-mouse conservation of noncoding features and disease-associated loci

Understanding the genetic aetiology of loci associated with a disease is crucial for developing preventative measures and effective treatments. Mouse models are used extensively to understand human pathobiology and mechanistic functions of disease-associated loci. However, the utility of mouse models is limited in part by evolutionary divergence in transcription regulation for pathways of interest. Here, we summarize the alignment of genomic (exonic and multi-cell regulatory) annotations alongside Mendelian and complex disease-associated variant sites between humans and mice. Our results highlight the importance of understanding evolutionary divergence in transcription regulation when interpreting functional studies using mice as models for human disease variants

The Chemerin-CMKLR1 Axis is Functionally important for Central Regulation of Energy Homeostasis

YesChemerin is an adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism, and has been hypothesized as a link between obesity and type II diabetes. In humans affected by obesity, chemerin gene expression in peripheral tissues and circulating levels are elevated. In mice, plasma levels of chemerin are upregulated by high-fat feeding and gain and loss of function studies show an association of chemerin with body weight, food intake and glucose homeostasis. Therefore, chemerin is an important blood-borne mediator that, amongst its other functions, controls appetite and body weight. Almost all studies of chemerin to date have focused on its release from adipose tissue and its effects on peripheral tissues with the central effects largely overlooked. To demonstrate a central role of chemerin, we manipulated chemerin signaling in the hypothalamus, a brain region associated with appetite regulation, using pharmacological and genetic manipulation approaches. Firstly, the selective chemerin receptor CMKLR1 antagonist α-NETA was administered i.c.v. to rats to test for an acute physiological effect. Secondly, we designed a short-hairpin-RNA (shRNA) lentivirus construct targeting expression of CMKLR1. This shRNA construct, or a control construct was injected bilaterally into the arcuate nucleus of male Sprague Dawley rats on high-fat diet (45%). After surgery, rats were maintained on high-fat diet for 2 weeks and then switched to chow diet for a further 2 weeks. We found a significant weight loss acutely and inhibition of weight gain chronically. This difference became apparent after diet switch in arcuate nucleus-CMKLR1 knockdown rats. This was not accompanied by a difference in blood glucose levels. Interestingly, appetite-regulating neuropeptides remained unaltered, however, we found a significant reduction of the inflammatory marker TNF-α suggesting reduced expression of CMKLR1 protects from high-fat diet induced neuroinflammation. In white and brown adipose tissue, mRNA expression of chemerin, its receptors and markers of adipogenesis, lipogenesis and brown adipocyte activation remained unchanged confirming that the effects are driven by the brain. Our behavioral analyses suggest that knockdown of CMKLR1 had an impact on object recognition. Our data demonstrate that CMKLR1 is functionally important for the central effects of chemerin on body weight regulation and neuroinflammation.This work was funded in part by the Academy of Medical Sciences, the Wellcome Trust, the Government of Business, Energy and Industrial Strategy and the British Heart Foundation and Diabetes United Kingdom [SBF004/1063] (GH), the Society for Endocrinology Equipment Grant (GH, RD), the University of Bradford (GH, KP, SK) and Nottingham Trent University (RD)