Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids

Why and When Beliefs Change

Why people do or do not change their beliefs has been a long-standing puzzle. Sometimes people hold onto false beliefs despite ample contradictory evidence; sometimes they change their beliefs without sufficient reason. Here, we propose that the utility of a belief is derived from the potential outcomes associated with holding it. Outcomes can be internal (e.g., positive/negative feelings) or external (e.g., material gain/loss), and only some are dependent on belief accuracy. Belief change can then be understood as an economic transaction in which the multidimensional utility of the old belief is compared against that of the new belief. Change will occur when potential outcomes alter across attributes, for example because of changing environments or when certain outcomes are made more or less salient

Galactic emission at 19 GHz

We cross-correlate a 19 GHz full sky Cosmic Microwave Background (CMB) survey with other maps to quantify the foreground contribution. Correlations are detected with the Diffuse Infrared Background Experiment (DIRBE) 240, 140 and 100 micron maps at high latitudes (|b|>30degrees), and marginal correlations are detected with the Haslam 408 MHz and the Reich & Reich 1420 MHz synchrotron maps. The former agree well with extrapolations from higher frequencies probed by the COBE DMR and Saskatoon experiments and are consistent with both free-free and rotating dust grain emission.Comment: 4 pages, with 4 figures included. Accepted for publication in ApJL. Color figure and links at http://www.sns.ias.edu/~angelica/foreground.html#19 or from [email protected]

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy

The propargyl rearrangement to functionalised allyl-boron and borocation compounds

A diverse range of Lewis acidic alkyl, vinyl and aryl boranes and borenium compounds that are capable of new carbon–carbon bond formation through selective migratory group transfer have been synthesised. Utilising a series of heteroleptic boranes [PhB(C6F5)2 (1), PhCH2CH2B(C6F5)2 (2), and E-B(C6F5)2(C6F5)C=C(I)R (R=Ph 3 a, nBu 3 b)] and borenium cations [phenylquinolatoborenium cation ([QOBPh][AlCl4], 4)], it has been shown that these boron-based compounds are capable of producing novel allyl- boron and boronium compounds through complex rearrangement reactions with various propargyl esters and carbamates. These reactions yield highly functionalised, synthetically useful boron substituted organic compounds with substantial molecular complexity in a one-pot reaction

Legitimacy in conflict: concepts, practices, challenges

The study of legitimacy in situations of conflict and peacebuilding has increased in recent years. However, current work on the topic adopts many assumptions, definitions, and understandings from classical legitimacy theory, which centers on the relationship between the nation-state and its citizens. In this introduction, we provide a detailed critical overview of current theories of legitimacy and legitimation and demonstrate why they have only limited applicability in conflict and post-conflict contexts, focusing on the three main areas that the articles included in this special issue examine: audiences for legitimacy, sources of legitimacy, and legitimation. In particular, we show how conflict and post-conflict contexts are marked by the fragmentation and personalization of power; the proliferation and fragmentation of legitimacy audiences; and ambiguity surrounding legitimation strategies

Determining the Quantitative Principles of T Cell Response to Antigenic Disparity in Stem Cell Transplantation

Alloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft vs. host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 generally presenting a greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and determine the risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation

Assessing a New Clue to How Much Carbon Plants Take Up

Current climate models disagree on how much carbon dioxide land ecosystems take up for photosynthesis. Tracking the stronger carbonyl sulfide signal could help

Self-help materials for the prevention of smoking relapse: study protocol for a randomized controlled trial.

BACKGROUND: Most people who stop smoking successfully for a few weeks will return to smoking again in the medium term. There are few effective interventions to prevent this relapse and none used routinely in clinical practice. A previous exploratory meta-analysis suggested that self-help booklets may be effective but requires confirmation. This trial aims to evaluate the effectiveness and cost-effectiveness of a set of self-help educational materials to prevent smoking relapse in the National Health Service (NHS) Stop Smoking Service. METHODS/DESIGN: This is an open, randomized controlled trial. The target population is carbon monoxide (CO) verified quitters at four weeks in the NHS stop smoking clinic (total sample size N = 1,400). The experimental intervention tested is a set of eight revised Forever Free booklets, including an introduction booklet and more extensive information on all important issues for relapse prevention. The control intervention is a leaflet that has no evidence to suggest it is effective but is currently given to some patients using NHS stop smoking services. Two follow-up telephone interviews will be conducted at three and 12 months after the quit date. The primary outcome will be prolonged abstinence from months four to 12 with no more than five lapses, confirmed by a CO test at the 12-month assessment. The secondary outcomes will be seven-day self-report point prevalence abstinence at three months and seven-day biochemically confirmed point prevalence abstinence at 12 months. To assess cost-effectiveness, costs will be estimated from a health service perspective and the EQ-5D will be used to estimate the QALY (Quality Adjusted Life Year) gain associated with each intervention. The comparison of smoking abstinence rates (and any other binary outcomes) between the two trial arms will be carried out using odds ratio as the outcome statistic and other related statistical tests. Exploratory subgroup analyses, including logistic regression analyses with interaction terms, will be conducted to investigate possible effect-modifying variables. DISCUSSION: The possible effect of self-help educational materials for the prevention of smoking relapse has important public health implications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36980856.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Microborings reveal alternating agitation, resting and sleeping stages of modern marine ooids

ABSTRACTOoids are abundant carbonate grains throughout much of Earth's history, but their formation is not well understood. Here, an in‐depth study of microbial bioerosion features of Holocene ooids from the Schooner Cays ooid shoals (Great Bahama Bank, Eleuthera, Bahamas) and the Shalil al Ud ooid shoals in the Gulf (Abu Dhabi, United Arab Emirates) is presented. No obvious differences were found in ooid size distribution, cortex layer thickness, the composition of nuclei or euendolithic community when comparing ooids from both locations. Microendolithic borings are present in most studied ooid surfaces, but the intensity of (micro‐)bioerosion varies significantly. Applying an epoxy vacuum cast‐embedding technique allowed the identification of ichnotaxa and their inferred producers (various genera of diatoms, cyanobacteria, coccolithophores and unspecified bacteria). Euendolithic taxa have specific low‐light tolerances and light optima. This implies that information about the relative bathymetry (seafloor versus burial within an ooid shoal) and ecology for ooid cortex formation can be obtained via the presence or absence of their respective ichnotaxa. The history of a statistically significant number of ooid cortices can be translated into dune dynamics and the temporal variations thereof by allocating the inferred index producer to a defined burial or light penetration zone. In this context, ooid formation can be divided into four stages: (i) an agitation stage in the water column, characterized by the colonization of grains by photoautotrophs; (ii) a resting stage, characterized by temporary burial of the ooid, leading to immobilization and a shift towards heterotrophs; (iii) a sleeping stage, characterized by prolonged burial and colonialization by organotrophs; and (iv) a reactivation stage, characterized by a resurfacing of the ooid and a subsequent shift towards photoautotrophs. The sleeping stage is presumably a stage of ooid degradation where bioerosion, mainly by heterotrophic fungi and bacteria is particularly active.</jats:p