The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms

Objectives: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. Methods: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1−/−) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. Results: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1−/− mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1−/− mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1−/− mice. Conclusions: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity

Gravitational Collapse with a Cosmological Constant

We consider the effect of a positive cosmological constant on spherical gravitational collapse to a black hole for a few simple, analytic cases. We construct the complete Oppenheimer-Snyder-deSitter (OSdS) spacetime, the generalization of the Oppenheimer-Snyder solution for collapse from rest of a homogeneous dust ball in an exterior vacuum. In OSdS collapse, the cosmological constant may affect the onset of collapse and decelerate the implosion initially, but it plays a diminishing role as the collapse proceeds. We also construct spacetimes in which a collapsing dust ball can bounce, or hover in unstable equilibrium, due to the repulsive force of the cosmological constant. We explore the causal structure of the different spacetimes and identify any cosmological and black hole event horizons which may be present.Comment: 7 pages, 10 figures; To appear in Phys. Rev.

CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.

Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy

Feed Quantity Effect on Carp Juveniles’ Plasma Protein and Immunoglobulin Levels

Plasma protein and immunoglobulin (Ig) levels in fish can be influenced by stress reaction, caused by some nutritional factors. This paper shows effects of different feed quantity on total protein and total Ig levels in blood of common carp (Cyprinus carpio) juveniles exposed to chronic stress conditions. The study was carried out in a recirculation aquaculture system (RAS) during 96 days. Carps (initial weight 6.43±0.02 g) were distributed into four groups in three replicate tanks, 40 fish per tank. The groups were formed according to the feed quantity applied: 2, 3, 4 and 5% of commercial extruded mixture in relation to the ichthyomass (i.e. groups I, II, III and IV respectively). According to the results, the mean values of total plasma proteins and Ig were highest in group IV and the lowest in group II (p<0.05). Total protein levels were influenced by feed quantity (p<0.05), and sampling time (p<0.001). Total Ig levels were influenced by duration of the experiment i.e. sampling time (p<0.001). In all groups the mean values of plasma proteins after two month of the experiment was increased (p<0.01), and the mean values of Ig in less fed groups I and II (p<0.05 and p<0.01, respectively). Total plasma proteins and Ig were not significantly affected by water quality parameters only in the group fed 2% of feed (group I). Significant positive correlation between total proteins and Ig was determined in each experimental group (p<0.01). In terms of reducing stress and ensuring welfare in carp juveniles, applied feed amount should match to the length of fish growing in the fish tanks, stocking density and capacity of the system for efficient water purification

Occupational exposure to blood and body fluids among health-care workers in Serbia

© 2014 S. Karger AG, Basel. Objectives: The aim of this study was to examine the epidemiology of occupational accidents and self-reported attitude of health-care workers (HCWs) in Serbia. Subjects and Methods: A cross-sectional study was conducted among HCWs in selected departments of five tertiary care hospitals and in one secondary care hospital in February 2012. A previously developed self-administered questionnaire was provided to HCWs who had direct daily contact with patients. χ2 test and Student's t test were used for statistical analysis of the data. Results: Of the 1,441 potential participants, 983 (68.2%) completed the questionnaire: 655 (66.7%) were nurses/medical technicians, 243 (24.7%) were physicians and 85 (8.6%) were other personnel. Of the 983 participants, 291 (29.6%) HCWs had had at least one accident during the previous year and 106 (40.2%) of them reported it to the responsible person. The highest prevalence (68.6%) of accidents was among nurses/technicians (p = 0.001). Accidents occurred more often in large clinical centers (81.1%; p < 0.001) and in the clinical ward, intensive care unit and operating theater (p = 0.003) than in other departments. Seventy-six (13.1%) nurses/medical technicians had an accident during needle recapping (p < 0.001). Of all the HCWs, 550 (55.9%) were fully vaccinated, including significantly more doctors (154, 63.4%) than participants from other job categories (p < 0.001). Conclusion: There was a relatively high rate of accidents among HCWs in our hospitals, most commonly amongst nurses and staff working in clinical wards, intensive care units and operating theaters. The most common types of accidents were needlestick injuries and accidents due to improper handling of contaminated sharp devices or occuring while cleaning instruments or by coming into contact with blood through damaged skin or through the conjunctiva/mucous membranes

Propagation of gravitational waves from slow motion sources in a Coulomb type potential

We consider the propagation of gravitational waves generated by slow motion sources in Coulomb type potential due to the mass of the source. Then, the formula for gravitational waveform including tail is obtained in a straightforward manner by using the spherical Coulomb function. We discuss its relation with the formula in the previous work.Comment: 13 pages, no figures, to be published in Phys. Rev.

The Field-Tuned Superconductor-Insulator Transition with and without Current Bias

The magnetic-field-tuned superconductor-insulator transition has been studied in ultrathin Beryllium films quench-condensed near 20 K. In the zero-current limit, a finite-size scaling analysis yields the scaling exponent product vz = 1.35 +/- 0.10 and a critical sheet resistance R_{c} of about 1.2R_{Q}, with R_{Q} = h/4e^{2}. However, in the presence of dc bias currents that are smaller than the zero-field critical currents, vz becomes 0.75 +/- 0.10. This new set of exponents suggests that the field-tuned transitions with and without dc bias currents belong to different universality classes.Comment: RevTex 4 pages, 4 figures, and 1 table minor change