Astrocytes in neuroendocrine systems: An overview

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record A class of glial cell, astrocytes are highly abundant in the CNS. In addition to maintaining tissue homeostasis, astrocytes regulate neuronal communication and synaptic plasticity. There is an ever-increasing appreciation that astrocytes are involved in the regulation of physiology and behaviour in normal and pathological states, including within neuroendocrine systems. Indeed, astrocytes are direct targets of hormone action in the CNS, via receptors expressed on their surface, and are also a source of regulatory neuropeptides, neurotransmitters, and gliotransmitters. Furthermore, as part of the neurovascular unit, astrocytes can regulate hormone entry into the CNS. This review is intended to provide an overview of how astrocytes are impacted by and contribute to the regulation of a diverse range of neuroendocrine systems: energy homeostasis and metabolism, reproduction, fluid homeostasis, the stress response, and circadian rhythms. This article is protected by copyright. All rights reserved.Medical Research Council (MRC)Diabetes UKUniversity of Exete

Absence of the mitochondrial translocator protein 18 kDa in mice does not affect body weight or food intake responses to altered energy availability

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.Changes in mitochondrial function in a variety of cells/tissues are critical for orchestrating systemic energy homeostasis and are linked to the development of obesity and many of its comorbidities. The mitochondrial translocator protein of 18 kDa (TSPO) is expressed in organs throughout the body, including the brain, liver, adipose tissue, gonads and adrenal glands, where it is implicated in regulating steroidogenesis and cellular metabolism. Prior work from our group and others has shown that, in rodents, TSPO levels are altered in adipose tissue by obesity and that modulation of TSPO activity may impact systemic glucose homeostasis. Furthermore, in vitro studies in a variety of cell types have implicated TSPO in mediating cellular energetics and substrate utilisation. Although mice with germline global TSPO deficiency (TSPO−/−) have no reported changes in body weight under standard husbandry conditions, we hypothesised that, given the roles of TSPO in regulating mitochondrial function and cellular metabolic flexibility, these animals may have alterations in their systemic response to altered energy availability, either nutritional excess or insufficiency. In agreement with published work, compared to wild-type (TSPO+/+) littermates, TSPO−/− mice of both sexes did not exhibit differences in body weight on standard chow. Furthermore, following a 12-hour overnight fast, there was no difference in weight loss or compensatory food intake during re-feeding. Five weeks of feeding a high-fat diet (HFD) did not reveal any impact of the absence of TSPO on body weight gain in either male or female mice. Basal blood glucose levels and glucose clearance in a glucose tolerance test were influenced by feeding a HFD diet but not by genotype. In conclusion, in the paradigms examined, germline global deletion of TSPO did not change the physiological response to deviations in systemic energy availability at the whole organism level.Medical Research Council (MRC)University of ExeterNational Institute for Health Research (NIHR

Immunometabolic changes in Glia – a potential role in the pathophysiology of obesity and diabetes

This is the final version. Available on open access from the publisher via the DOI in this recordChronic low-grade inflammation is a feature of the pathophysiology of obesity and diabetes in the CNS as well as peripheral tissues. Glial cells are critical mediators of the response to inflammation in the brain. Key features of glia include their metabolic flexibility, sensitivity to changes in the CNS microenvironment, and ability to rapidly adapt their function accordingly. They are specialised cells which cooperate to promote and preserve neuronal health, playing important roles in regulating the activity of neuronal networks across the brain during different life stages. Increasing evidence points to a role of glia, most notably astrocytes and microglia, in the systemic regulation of energy and glucose homeostasis in the course of normal physiological control and during disease. Inflammation is an energetically expensive process that requires adaptive changes in cellular metabolism and, in turn, metabolic intermediates can also have immunomodulatory actions. Such “immunometabolic” changes in peripheral immune cells have been implicated in contributing to disease pathology in obesity and diabetes. This review will discuss the evidence for a role of immunometabolic changes in glial cells in the systemic regulation of energy and glucose homeostasis, and how this changes in the context of obesity and diabetes.Medical Research Council (MRC)European Foundation for the Study of Diabete

Characterizing Ultraviolet and Infrared Observational Properties for Galaxies. I. Influences of Dust Attenuation and Stellar Population Age

The correlation between infrared-to-ultraviolet luminosity ratio and ultraviolet color, i.e. the IRX-UV relation, was regarded as a prevalent recipe for correcting extragalactic dust attenuation. Considerable dispersion in this relation discovered for normal galaxies, however, complicates its usability. In order to investigate the cause of the dispersion, in this paper, we select five nearby spiral galaxies, and perform spatially resolved studies on each of the galaxies, with a combination of ultraviolet and infrared imaging data. We measure all positions within each galaxy and divide the extracted regions into young and evolved stellar populations. By means of this approach, we attempt to discover separate effects of dust attenuation and stellar population age on the IRX-UV relation for individual galaxies. In this work, in addition to dust attenuation, stellar population age is interpreted to be another parameter in the IRX-UV function, and the diversity of star formation histories is suggested to disperse the age effects. At the same time, strong evidence shows the necessity of more parameters in the interpretation of observational data, such as variations in attenuation/extinction law. Fractional contributions of different components to the integrated luminosities of the galaxies suggest that the integrated measurements of galaxies which comprise different populations would weaken the effect of the age parameter on IRX-UV diagrams. The dependance of the IRX-UV relation on luminosity and radial distance in galaxies presents weak trends, which offers an implication of selective effects. The two-dimensional maps of the UV color and the infrared-to-ultraviolet ratio are displayed and show a disparity in the spatial distributions between the two parameters in galaxies, which offers a spatial interpretation of the scatter in the IRX-UV relation.Comment: 23 pages, 27 figures, 4 tables; accepted for publication in The Astrophysical Journal; re-typesetted in the emulateapj style; minor corrections in the figure symbols and in the tex

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

The Burden of Invasive Bacterial Infections in Pemba, Zanzibar

BACKGROUND: We conducted a surveillance study to determine the leading causes of bloodstream infection in febrile patients seeking treatment at three district hospitals in Pemba Island, Zanzibar, Tanzania, an area with low malaria transmission. METHODS: All patients above two months of age presenting to hospital with fever were screened, and blood was collected for microbiologic culture and malaria testing. Bacterial sepsis and malaria crude incidence rates were calculated for a one-year period and were adjusted for study participation and diagnostic sensitivity of blood culture. RESULTS: Blood culture was performed on 2,209 patients. Among them, 166 (8%) samples yielded bacterial growth; 87 (4%) were considered as likely contaminants; and 79 (4%) as pathogenic bacteria. The most frequent pathogenic bacteria isolated were Salmonella Typhi (n = 46; 58%), followed by Streptococcus pneumoniae (n = 12; 15%). The crude bacteremia rate was 6/100,000 but when adjusted for potentially missed cases the rate may be as high as 163/100,000. Crude and adjusted rates for S. Typhi infections and malaria were 4 and 110/100,000 and 4 and 47/100,000, respectively. Twenty three (51%), 22 (49%) and 22 (49%) of the S. Typhi isolates were found to be resistant toward ampicillin, chloramphenicol and cotrimoxazole, respectively. Multidrug resistance (MDR) against the three antimicrobials was detected in 42% of the isolates. CONCLUSIONS: In the presence of very low malaria incidence we found high rates of S. Typhi and S. pneumoniae infections on Pemba Island, Zanzibar. Preventive measures such as vaccination could reduce the febrile disease burden

The Faces in Infant-Perspective Scenes Change over the First Year of Life

Mature face perception has its origins in the face experiences of infants. However, little is known about the basic statistics of faces in early visual environments. We used head cameras to capture and analyze over 72,000 infant-perspective scenes from 22 infants aged 1-11 months as they engaged in daily activities. The frequency of faces in these scenes declined markedly with age: for the youngest infants, faces were present 15 minutes in every waking hour but only 5 minutes for the oldest infants. In general, the available faces were well characterized by three properties: (1) they belonged to relatively few individuals; (2) they were close and visually large; and (3) they presented views showing both eyes. These three properties most strongly characterized the face corpora of our youngest infants and constitute environmental constraints on the early development of the visual system

Selective gene silencing by viral delivery of short hairpin RNA

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells