Glucocorticoid Receptor and Adipocyte Biology.

Glucocorticoids are steroid hormones that play a key role in metabolic adaptations during stress, such as fasting and starvation, in order to maintain plasma glucose levels. Excess and chronic glucocorticoid exposure, however, causes metabolic syndrome including insulin resistance, dyslipidemia, and hyperglycemia. Studies in animal models of metabolic disorders frequently demonstrate that suppressing glucocorticoid signaling improves insulin sensitivity and metabolic profiles. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. The adipocyte is one cell type that contributes to whole body metabolic homeostasis under the influence of GR. Glucocorticoids' functions on adipose tissues are complex. Depending on various physiological or pathophysiological states as well as distinct fat depots, glucocorticoids can either increase or decrease lipid storage in adipose tissues. In rodents, glucocorticoids have been shown to reduce the thermogenic activity of brown adipocytes. However, in human acute glucocorticoid exposure, glucocorticoids act to promote thermogenesis. In this article, we will review the recent studies on the mechanisms underlying the complex metabolic functions of GR in adipocytes. These include studies of the metabolic outcomes of adipocyte specific GR knockout mice and identification of novel GR primary target genes that mediate glucocorticoid action in adipocytes

Glucocorticoid receptor action in metabolic and neuronal function [version 1; referees: 3 approved]

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them

Copper Mining and Environmental Costs in Dominica

A proposal from an international mining company to establish a copper mining operation in the Caribbean island of Dominica could be highly favourable, given the potential for financial benefits associated with such a project. On the downside, such projects are often associated with environmental damage. The area targeted for this copper mine was a rainforest in the north-eastern portion of Dominica occupying around 12 percent of the island’s total land area. A critical question is therefore whether copper mining could be a viable alternative to agrarian uses of the targeted area, if both financial and environmental costs are taken into consideration. A Contingent Valuation Survey of Dominicans and Visitors allowed for inclusion of non-market costs in the analysis. Cost-Benefit and sensitivity analyses were carried out to assess project feasibility. The results indicated that NPV was negative under conservative assumptions. NPV was sensitive to changes in the price of copper and the inclusion of environmental costs did affect the level of price increase required to make NPV positive.Copper mining, Dominica, environmental costs, sensitivity analysis, cost-benefit, Agribusiness, Environmental Economics and Policy, Financial Economics,

Individual Differences in Phonological Feedback Effects: Evidence for the Orthographic Recoding Hypothesis of Orthographic Learning

Share (1995) has proposed phonological recoding (the translation of letters into sounds) as a self-teaching mechanism through which readers establish complete lexical representations. More recently, McKague et al. (2008) proposed a similar role for orthographic recoding, i.e., feedback from sounds to letters, in building and refining lexical representations. We reasoned that an interaction between feedback consistency measures and spelling ability in a spelling decision experiment would lend support to this hypothesis. In a linear mixed effects logistic regression of accuracy data this interaction was significant. Better spellers but not poorer spellers were immune to feedback effects in deciding if a word is spelled correctly, which is consistent with McKague et al.’s prediction that the impact of phonological feedback on word recognition will diminish when the orthographic representation for an item is fully specified. The study demonstrates the importance of considering individual differences when investigating the role of phonology in reading

Lexical Stress and Linguistic Predictability Influence Proofreading Behavior

There is extensive evidence that the segmental (i.e., phonemic) layer of phonology is routinely activated during reading, but little is known about whether phonological activation extends beyond phonemes to subsegmental layers (which include articulatory information, such as voicing) and suprasegmental layers (which include prosodic information, such as lexical stress). In three proofreading experiments, we show that spelling errors are detected more reliably in syllables that are stressed than in syllables that are unstressed if comprehension is a goal of the reader, indicating that suprasegmental phonology is both active during silent reading and can influence orthographic processes. In Experiment 1, participants received instructions to read for both errors and comprehension, and we found that the effect of lexical stress interacted with linguistic predictability, such that detection of errors in more predictable words was aided by stress but detection of errors in less predictable words was not. This finding suggests that lexical stress patterns can be accessed prelexically if an upcoming word is sufficiently predictable from context. Participants with stronger vocabularies showed decreased effects of stress on task performance, which is consistent with previous findings that more skilled readers are less swayed by phonological information in decisions about orthographic form. In two subsequent experiments, participants were instructed to read only for errors (Experiment 2) or only for comprehension (Experiment 3); the effect of stress disappeared when participants read for errors and reappeared when participants read for comprehension, reconfirming our hypothesis that predictability is a driver of lexical stress effects. In all experiments, errors were detected more reliably in words that were difficult to predict from context than in words that were highly predictable. Taken together, this series of experiments contributes two important findings to the field of reading and cognition: (1) The prosodic property of lexical stress can influence orthographic processing, and (2) Predictability inhibits the detection of errors in written language processing.NICHD grant R01HD058566-02 Author fees paid for by the Northern Illinois University Libraries Open Access Publishing Fun

Universal reading processes are modulated by language and writing system

The connections among language, writing system, and reading are part of what confronts a child in learning to read. We examine these connections in addressing how reading processes adapt to the variety of written language and how writing adapts to language. The first adaptation (reading to writing), as evidenced in behavioral and neuroscience data, is achieved through a universal constraint that language places on writing and through the tuning of reading procedures imposed by specific features of writing systems. Children acquire skill in reading through increasing specialization of procedures tuned to their writing system, while also acquiring more general (universal) procedures that serve language mapping and cognitive control. For the second adaption (writing to language), we present examples from several languages to suggest that writing systems tend to fit their linguistic properties, thus providing adaptive variation in writing-to-language mapping. We suggest that this writing-language fit facilitates the child’s learning how his or her writing system works

Reducing the Effects of Unequal Number of Games on Rankings

Ranking is an important mathematical process in a variety of contexts such as information retrieval, sports and business. Sports ranking methods can be applied both in and beyond the context of athletics. In both settings, once the concept of a game has been defined, teams (or individuals) accumulate wins, losses, and ties, which are then factored into the ranking computation. Many settings involve an unequal number of games between competitors. This paper demonstrates how to adapt two sports rankings methods, the Colley and Massey ranking methods, to settings where an unequal number of games are played between the teams. In such settings, the standard derivations of the methods can produce nonsensical rankings. This paper introduces the idea of including a super-user into the rankings and considers the effect of this fictitious player on the ratings. We apply such techniques to rank batters and pitchers in Major League baseball, professional tennis players, and participants in a free online social game. The ideas introduced in this paper can further the scope that such methods are applied and the depth of insight they offer

Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations

We have investigated the effects of duplex length, sequence, salt concentration and superhelical density on the conformation of DNA nanocircles containing up to 178 base pairs using atomistic molecular dynamics simulation. These calculations reveal that the partitioning of twist and writhe is governed by a delicate balance of competing energetic terms. We have identified conditions which favour circular, positively or negatively writhed and denatured DNA conformations. Our simulations show that AT-rich DNA is more prone to denaturation when subjected to torsional stress than the corresponding GC containing circles. In contrast to the behaviour expected for a simple elastic rod, there is a distinct asymmetry in the behaviour of over and under-wound DNA nanocircles. The most biologically relevant negatively writhed state is more elusive than the corresponding positively writhed conformation, and is only observed for larger circles under conditions of high electrostatic screening. The simulation results have been summarised by plotting a phase diagram describing the various conformational states of nanocircles over the range of circle sizes and experimental conditions explored during the study. The changes in DNA structure that accompany supercoiling suggest a number of mechanisms whereby changes in DNA topology in vivo might be used to influence gene expression