Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Antifascism, the 1956 Revolution and the politics of communist autobiographies in Hungary 1944-2000

This is a postprint of an article whose final and definitive form has been published in Europe-Asia Studies © 2006 University of Glasgow; Europe-Asia Studies is available online at http://www.informaworld.com.Using oral history, this contribution explores the reshaping of individuals' public and private autobiographies in response to different political environments. In particular, it analyses the testimony of those who were communists in Hungary between 1945 and 1956, examining how their experiences of fascism, party membership, the 1956 Revolution and the collapse of communism led them in each case to refashion their life stories. Moreover, it considers how their biographies played varying functions at different points in their lives: to express identification with communism, to articulate resistance and to communicate ambition before 1956; to protect themselves from the state after 1956; and to rehabilitate themselves morally in a society which stigmatised them after 1989.I didn't use this word 'liberation' (felszabadulás), because in 1956 my life really changed. Everybody's lives went through a great change, but mine especially. … I wasn't disgusted with myself that I had called the arrival of the Red Army in 1945 a liberation, but [after 1956] I didn't use it anymore

Adapting to Expanding and Contracting Cities, Book of Abstracts, 6th Fabos Conference on Landscape and Greenway Planning, March 28-30, 2019, Amherst, MA.

The Fábos Conference on Landscape and Greenway Planning is held every three years to bring together experts who are influencing landscape planning, policy making and greenway planning from the local to international level. It is intended to highlight recent trends and expand the literature about landscape and greenway planning. The aim is to explore how landscape architects and planners from different countries have approached greenway planning and to understand how greenways have been tailored to each county’s unique geographical, cultural, and political circumstances. The theme for the 2019 conference, Urban Greenway Planning: Adapting to Expanding and Contracting Cities, explores the social and ecological potential of linear green spaces in urban areas that are experiencing decline or those that are booming. We look to understand the variety of ways in which urban greenways are conceived, designed, built, used, and maintained in cities across the globe in response to economic and demographic trends

The effect of kinesio taping versus stretching techniques on muscle soreness, and flexibility during recovery from nordic hamstring exercise

WOS: 000396418800007PubMed ID: 28167188The purpose of this study was to examine the effects of static stretching, proprioceptive neuromuscular facilitation (PNF) stretching, or kinesio taping (KT) on muscle soreness and flexibility during recovery from exercise. Sixty-five females were randomly assigned to four groups: PNF stretching (n = 15), static stretching (n = 16), KT (n = 17), and control (n = 17). All participants performed nordic hamstring exercise (5 sets of 8 repetitions). In all groups, hamstring flexibility at 24 h and 48 h was not changed from baseline (p > .05). The muscle soreness was measured higher at 48 h post-exercise compared with baseline in the control group (p = .04) and at 24 h post-exercise compared with baseline in the PNF group (p .05). The KT application and pre-exercise stretching have no contribute to flexibility at 24 h and 48 h after exercise, but may attenuate muscle soreness. (C) 2016 Elsevier Ltd. All rights reserved

Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon

We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline

An australian audit of vaccination status in children and adolescents with inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Children and adolescents with inflammatory bowel disease (IBD) are at increased risk of vaccine preventable diseases (VPD). This includes invasive pneumococcal disease and influenza. The primary aim of this study was to describe compliance with current Australian guidelines for vaccination of children and adolescents diagnosed with IBD. A secondary aim was to review the serological screening for VPD.</p> <p>Methods</p> <p>A random sample of patients (0-18 years at diagnosis), were selected from the Victoria Australia state based Pediatric Inflammatory Bowel Disease Register. A multi-faceted retrospective review of immunization status was undertaken, with hospital records audited, a telephone interview survey conducted with consenting parents and the vaccination history was checked against the primary care physician and Australian Childhood Immunization Register (ACIR) records. The routine primary childhood vaccinations and administration of the recommended additional influenza and pneumococcal vaccines was clarified.</p> <p>Results</p> <p>This 2007 audit reviewed the immunization status of 101individuals on the Victorian Pediatric IBD database. Median age at diagnosis was 12.1 years, 50% were on active immunosuppressive therapy. 90% (38/42) [95% confidence intervals (CI) 77%; 97%] with complete immunization information were up-to-date with routine primary immunizations. Only 5% (5/101) [95% CI 2%; 11%] received a recommended pneumococcal vaccine booster and 10% (10/101) [95% CI 5%; 17%] had evidence of having ever received a seasonal influenza vaccine. Those living in rural Victoria (p = 0.005) and younger at the age of diagnosis (p = 0.002) were more likely to have ever received an influenza vaccine Serological testing, reviewing historical protection from VPD, identified 18% (17/94) with evidence of at least one serology sample.</p> <p>Conclusion</p> <p>This study highlights poor compliance in IBD patients for additional recommended vaccines. A multi-faceted approach is required to maximize protection from VPD in this vulnerable special risk population.</p

Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis

Contains fulltext : 79505.pdf (publisher's version ) (Open Access

Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors

Fibroblasts derived from the progeroid Werner syndrome show reduced replicative lifespan and a "stressed" morphology, both alleviated using the MAP kinase inhibitor SB203580. However, interpretation of these data is problematical because although SB203580 has the stress-activated kinases p38 and JNK1/2 as its preferred targets, it does show relatively low overall kinase selectivity. Several lines of data support a role for both p38 and JNK1/2 activation in the control of cellular proliferation and also the pathology of diseases of ageing, including type II diabetes, diseases to which Werner Syndrome individuals are prone, thus making the use of JNK inhibitors attractive as possible therapeutics. We have thus tested the effects of the widely used JNK inhibitor SP600125 on the proliferation and morphology of WS cells. In addition we synthesised and tested two recently described aminopyridine based inhibitors. SP600125 treatment resulted in the cessation of proliferation of WS cells and resulted in a senescent-like cellular phenotype that does not appear to be related to the inhibition of JNK1/2. In contrast, use of the more selective aminopyridine CMPD 6o at concentrations that fully inhibit JNK1/2 had a positive effect on cellular proliferation of immortalised WS cells, but no effect on the replicative lifespan of primary WS fibroblasts. In addition, CMPD 6o corrected the stressed WS cellular morphology. The aminopyridine CMPD 6r, however, had little effect on WS cells. CMDP 6o was also found to be a weak inhibitor of MK2, which may partially explain its effects on WS cells, since MK2 is known to be involved in regulating cellular morphology via HSP27 phosphorylation, and is thought to play a role in cell cycle arrest. These data suggest that total JNK1/2 activity does not play a substantial role in the proliferation control in WS cells

Left ventricular diastolic dyssynchrony assessed with phase analysis of gated myocardial perfusion SPECT: a comparison with tissue Doppler imaging

Cardiac Dysfunction and Arrhythmia