Food restriction reverses the hyper-muscular phenotype and force generation capacity deficit of the myostatin null mouse

Food restriction has a great impact on skeletal muscle mass by inducing muscle protein breakdown to provide substrates for energy production through gluconeogenesis. Genetic models of hyper-muscularity interfere with the normal balance between protein synthesis and breakdown which eventually results in extreme muscle growth. Mutations or deletions in the myostatin gene result in extreme muscle mass. Here we evaluated the impact of food restriction for a period of 5 weeks on skeletal muscle size (i.e., fibre cross-sectional area), fibre type composition and contractile properties (i.e., tetanic and specific force) in myostatin null mice. We found that this hyper-muscular model was more susceptible to catabolic processes than wild type mice. The mechanism of skeletal muscle mass loss was examined and our data shows that the myostatin null mice placed on a low calorie diet maintained the activity of molecules involved in protein synthesis and did not up-regulate the expression of genes pivotal in ubiquitin-mediated protein degradation. However, we did find an increase in the expression of genes associated with autophagy. Surprisingly, the reduction on muscle size was followed by improved tetanic and specific force in the null mice compared to wild type mice. These data provide evidence that food restriction may revert the hyper-muscular phenotype of the myostatin null mouse restoring muscle function.

Examining the large-scale spatial coherence of European drought using regional indicators of precipitation and streamflow deficit

Droughts tend to evolve slowly and affect large areas simultaneously, which suggests that improved understanding of spatial coherence of drought would enable better mitigation of drought impacts through enhanced monitoring and forecasting strategies. This study employs an up-to-date dataset of over 500 river flow time series from 11 European countries, along with a gridded precipitation dataset, to examine the spatial coherence of drought in Europe using regional indicators of precipitation and streamflow deficit. The drought indicators were generated for 24 homogeneous regions and, for selected regions, historical drought characteristics were corroborated with previous work. The spatial coherence of drought characteristics was then examined at a European scale. Historical droughts generally have distinctive signatures in their spatio-temporal development, so there was limited scope for using the evolution of historical events to inform forecasting. Rather, relationships were explored in time series of drought indicators between regions. Correlations were generally low, but multivariate analyses revealed broad continental-scale patterns, which appear to be related to large-scale atmospheric circulation indices (in particular, the North Atlantic Oscillation and the East Atlantic West Russia pattern). A novel methodology for forecasting was developed (and demonstrated with reference to the United Kingdom), which predicts drought from drought i.e. uses spatial coherence of drought to facilitate early warning of drought in a target region, from drought which is developing elsewhere in Europe.Whilst the skill of the methodology is relatively modest at present, this approach presents a potential new avenue for forecasting, which offers significant advantages in that it allows prediction for all seasons, and also shows some potential for forecasting the termination of drought conditions.

Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology.

Pre-conditioning the epigenetic response to high vapor pressure deficit increases the drought tolerance of Arabidopsis thaliana

Epigenetic modification of the genome via cytosine methylation is a dynamic process that responds to changes in the growing environment. This modification can also be heritable. The combination of both properties means that there is the potential for the life experiences of the parental generation to modify the methylation profiles of their offspring and so potentially to ‘pre-condition’ them to better accommodate abiotic conditions encountered by their parents. We recently identified high vapor pressure deficit (vpd)-induced DNA methylation at two gene loci in the stomatal development pathway and an associated reduction in leaf stomatal frequency.1 Here, we test whether this epigenetic modification pre-conditioned parents and their offspring to the more severe water stress of periodic drought. We found that three generations of high vpd-grown plants were better able to withstand periodic drought stress over two generations. This resistance was not directly associated with de novo methylation of the target stomata genes, but was associated with the cmt3 mutant’s inability to maintain asymmetric sequence context methylation. If our finding applies widely, it could have significant implications for evolutionary biology and breeding for stressful environments.

On judging the credibility of climate predictions

Incorporating a prediction into future planning and decision making is advisable only if we have judged the prediction’s credibility. This is notoriously difficult and controversial in the case of predictions of future climate. By reviewing epistemic arguments about climate model performance, we discuss how to make and justify judgments about the credibility of climate predictions. We propose a new bounding argument that justifies basing such judgments on the past performance of possibly dissimilar prediction problems. This encourages a more explicit use of data in making quantitative judgments about the credibility of future climate predictions, and in training users of climate predictions to become better judges of credibility. We illustrate the approach using decadal predictions of annual mean, global mean surface air temperature.

Varieties of semantic ‘access’ deficit in Wernicke’s aphasia and semantic aphasia

Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia (SA), characterised by poor executive control of semantic processing across verbal and nonverbal modalities, and (ii) Wernicke’s aphasia (WA), associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well-understood. Both patient groups exhibit some type of semantic ‘access’ deficit, as opposed to the ‘storage’ deficits observed in semantic dementia. Nevertheless, existing descriptions suggest these patients might have different varieties of ‘access’ impairment – related to difficulty resolving competition (in SA) vs. initial activation of concepts from sensory inputs (in WA). We used a case-series design to compare WA and SA patients on Warrington’s paradigmatic assessment of semantic ‘access’ deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic ‘blocking’ effects). WA and SA patients were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability – one that mapped onto classical ‘syndromes’ and one that did not – predicted aspects of the semantic ‘access’ deficit. Both SA and WA cases showed multimodal semantic impairment, although as expected the WA group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially beneficial effects of stimulus repetition: WA cases showed initial improvement with repetition of words and pictures, while in SA, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the harmful effects of repetition: the ability to re-select both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, SA and WA patients have partially distinct impairment of semantic ‘access’ but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks.

Democratic Deficit in the EU : Towards Parliamentary Democracy?!

Nowadays, the western societies are based on parliamentary democracy. Therefore, weak legislative power of the European Parliament is alleged for the democratic deficit in the EU. How it can be possible that the parliamentary democracy which is practiced on the national level can be achieved beyond the nation-states without diminishing the democracy at the nation-states? If not, how legitimacy can be obtained so that the continued existence and expansion of the EU should be justified? Since expectations for democratization of the EU are still unmet, finding answers to the actual questions is a great appeal. The thesis will explore the fundamental debates and arguments contributing to the democracy in the EU through the parliaments. I will try to reflect to the different ways of thinking and the prospects of establishing parliamentary democracy beyond the nation states.

Inflation targeting, credibility and confidence crises

We study the interplay between the central bank transparency, its credibility, and the ination target level. Based on a model developed in the spirit of the global games literature, we argue that whenever a weak central bank adopts a high degree of transparency and a low target level, a bad and self conrmed type of equilibrium may arise. In this case, an over-the-target ination becomes more likely. The central bank is considered weak when favorable state of nature is required for the target to be achieved. On the other hand, if a weak central bank opts for less ambitious goals, namely lower degree of transparency and higher target level, it may avoid condence crises and ensure a unique equilibrium for the expected ination. Moreover, even after ruling out the possibility of condence crises, less ambitious goals may be desirable in order to attain higher credibility and hence a better coordination of expectations. Conversely, a low target level and a high central bank transparency are desirable whenever the economy has strong fundamentals and the target can be fullled in many states of nature.

Endogenous time-dependent rules and the costs of disinflation with imperfect credibility

This paper examines the output effects of monetary disinflation in a model with endogenous time-dependent pricing rules and imperfect credibility of the disinflation policy. We find that these features interact to generate an additional effect on top f the ones obtained with either endogenous time-dependent rules (Bonomo and Carvalho, 2003) or imperfect credibility (Ball, 1995) in isolation. This results in higher output costs of monetary disinflation.

The effect of using claim confirming product cues on the product claim credibility: is seeing believing?

The Cue Utilization Theory establishes that all products are made of multiples cues that may be seen as surrogates for the intangible attributes that make up any given product. However, the results of many years of research have yet yielded little consensus as to the impact generated by the use of such cues. This research aims to contribute to the discussion about the importance of intrinsic cues by investigating the effects that the use of product cues that confirm the product claim may have on Claim Credibility (measured through Ad Credibility), and also on consumers’ Purchase Intention and Perceived Risk toward the product. An experiment was designed to test such effects and the results suggest the effects of the use of Claim Confirming Product Cues depend on consumer’s level of awareness about such cue, and that when consumers are aware of it, Ad Credibility and Purchase Intention increase, as Perceived Risk decreases. Such results may have implications to academicians and practitioners, as well as may provide insights for future research.

Optimal-state-dependent rules, credibility, and inflationary inertia

This paper examines the output losses caused by disinflation and the role of credibility in a model where pricing mIes are optimal and individual prices are rigid. Individual nominal rigidity is modeled as resulting from menu costs. The interaction between optimal pricing mIes and credibility is essential in determining the inflationary inertia. A continued period of high inflation generates an asymmetric distribution of price deviations, with more prices that are substantially lower than their desired leveIs than prices that are substantially higher than the optimal ones. When disinflation is not credible, inflationary inertia is engendered by this asymmetry: idiosyncratic shocks trigger more upward than downward adjustments. A perfect1y credible disinflation causes an immediate change of pricing rules which, by rendering the price deviation distribution less asymmetric, practically annihilates inflationary inertia. An implication of our model is that stabilization may be sucessful even when credibility is low, provided that it is preceded by a mechanism of price alignment. We also develop an analytical framework for analyzing imperfect credibility cases.