| 1. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Gallo-Payet, Nicole, et al.
(författare)
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AT2 Receptor Agonists : Exploiting the Beneficial Arm of Ang II Signaling
- 2012
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Ingår i: current hypertension reviews. - : bentham science publishers. - 1573-4021. ; 8:1, s. 47-59
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Forskningsöversikt (refereegranskat)abstract
- In the classical view, the hormone angiotensin II (Ang II) mediates its action via two major receptors, namely the Ang II type-1 receptor (AT1R) and the type-2 receptor (AT2R). Several recent reviews implicate the renin-angiotensin system (RAS) in various aspects of adipose tissue physiology and dysfunction. Research on AT2R has long been hampered by at least three potential challenges, (i) the low expression level of the AT2R in the adult, (ii) the atypical signaling pathways of AT2R and (iii) the absence of appropriate selective ligands. Indeed, apart a few exceptions, the role of the AT2R was in fact revealed by the results of simultaneous treatment with Ang II and AT1R blockers or in AT2Rdeficient mice. The first aim of this review is to summarize current paradigms concerning the role of the AT2R in adipocyte differentiation and in metabolic disorders related to insulin resistance and type 2 diabetes. Secondly, we will highlight the potential utility of selective AT2R agonists in clarifying potential roles of the AT2R in adipocyte physiology. We summarized our findings using a selective and high affinity nonpeptide ligand of the AT2R and demonstrate that AT2R is involved in adipocyte differentiation and may improve insulin sensitivity in a model of insulin resistance, in addition to increase vasodilation and reduce inflammation in adipose tissue. Thus the recent development of orally active, selective AT2R agonists should facilitate efforts to elucidate the distinct roles of the AT2R in physiology, including adipocyte physiology.
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| 3. |
- Landegren, Nils, et al.
(författare)
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Transglutaminase 4 as a prostate autoantigen in male subfertility
- 2015
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 7:292
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.
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| 4. |
- Shum, Michael, et al.
(författare)
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Angiotensin II type 2 receptor promotes adipocyte differentiation and restores adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 304:2, s. E197-E210
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II type 2 receptor promotes adipocyte differentiation and restores adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats. Am J Physiol Endocrinol Metab 304: E197-E210, 2013. First published November 13, 2012; doi:10.1152/ajpendo.00149.2012.-This study was aimed at establishing whether specific activation of angiotensin II (ANG II) type 2 receptor (AT2R) modulates adipocyte differentiation and function. In primary cultures of subcutaneous (SC) and retroperitoneal (RET) preadipocytes, both AT2R and AT1R were expressed at the mRNA and protein level. Cells were stimulated with ANG II or the AT2R agonist C21/M24, alone or in the presence of the AT1R antagonist losartan or the AT2R antagonist PD123,319. During differentiation, C21/M24 increased PPA gamma expression in both RET and SC preadipocytes while the number of small lipid droplets and lipid accumulation solely increased in SC preadipocytes. In mature adipocytes, C21/M24 decreased the mean size of large lipid droplets. Upon abolishment of AT2R expression using AT2R-targeted shRNAs, expressions of AT2R, aP2, and PPAR gamma remained very low, and cells were unable to differentiate. In Wistar rats fed a 6-wk high-fat/high-fructose (HFHF) diet, a significant shift toward larger adipocytes was observed in RET and SC adipose tissue depots. C21/M24 treatments for 6 wk restored normal adipocyte size distribution in both these tissue depots. Moreover, C21/M24 and losartan decreased hyperinsulinemia and improved insulin sensitivity impaired by HFHF diet. A strong correlation between adipocyte size area and glucose infusion rate during euglycemic-hyperinsulinemic clamp was observed. These results indicate that AT2R is involved in early adipocyte differentiation, while in mature adipocytes and in a model of insulin resistance AT2R activation restores normal adipocyte morphology and improves insulin sensitivity.
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