Does self-control improve with practice? Evidence from a 6-week training program

Can self-control be improved through practice? Several studies have found that repeated practice of tasks involving self-control improves performance on other tasks relevant to self-control. However, in many of these studies, improvements after training could be attributable to methodological factors (e.g., passive control conditions). Moreover, the extent to which the effects of training transfer to real-life settings is not yet clear. In the present research, participants (N = 174) completed a 6-week training program of either cognitive or behavioral self-control tasks. We then tested the effects of practice on a range of measures of self-control, including lab-based and real-world tasks. Training was compared to both active and no-contact control conditions. Despite high levels of adherence to the training tasks, there was no effect of training on any measure of self-control. Trained participants did not, for example, show reduced ego depletion effects, become better at overcoming their habits, or report exerting more self-control in everyday life. Moderation analyses found no evidence that training was effective only among particular groups of participants. Bayesian analyses suggested that the data was more consistent with a null effect of training on self-control than with previous estimates of the effect of practice. The implication is that training self-control through repeated practice does not result in generalized improvements in self-control

The Endosymbiont Wolbachia pipientis Induces the Expression of Host Antioxidant Proteins in an Aedes albopictus Cell Line

Wolbachia are obligate intracellular bacteria which commonly infect arthropods. They are maternally inherited and capable of altering host development, sex determination, and reproduction. Reproductive manipulations include feminization, male-killing, parthenogenesis, and cytoplasmic incompatibility. The mechanism by which Wolbachia avoid destruction by the host immune response is unknown. Generation of antimicrobial peptides (AMPs) and reactive oxygen species (ROS) by the host are among the first lines of traditional antimicrobial defense. Previous work shows no link between a Wolbachia infection and the induction of AMPs. Here we compare the expression of protein in a cell line naturally infected with Wolbachia and an identical cell line cured of the infection through the use of antibiotics. Protein extracts of each cell line were analyzed by two dimensional gel electrophoresis and LC/MS/MS. Our results show the upregulation of host antioxidant proteins, which are active against ROS generated by aerobic cell metabolism and during an immune response. Furthermore, flow cytometric and microscopic analysis demonstrates that ROS production is significantly greater in Wolbachia-infected mosquito cells and is associated with endosymbiont-containing vacuoles located in the host cell cytoplasm. This is the first empirical data supporting an association between Wolbachia and the insect antioxidant system

MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU

BACKGROUND: Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. METHODS AND FINDINGS: In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. CONCLUSIONS: Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation

O novo Museu de Arqueologia e Etnografia

Treatment personalisation remains an unmet need in oropharynx cancer (OPC). We aimed to determine whether gene expression signatures improved upon clinico-pathological predictors of outcome in OPC. The clinico-pathological predictors, AJCC version 7 (AJCC 7), AJCC 8, and a clinical algorithm, were assessed in 4 public series of OPC (n = 235). Literature review identified 16 mRNA gene expression signatures of radiosensitivity, HPV status, tumour hypoxia, and microsatellite instability. We quality tested signatures using a novel sigQC methodology, and added signatures to clinico-pathological variables as predictors of survival, in univariate and multivariate analyses. AJCC 7 Stage was not predictive of recurrence-free survival (RFS) or overall survival (OS). AJCC 8 significantly predicted RFS and OS. Gene signature quality was highly variable. Among HPV-positive cases, signatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant underlying inter-tumour biological heterogeneity, but did not show prognostic significance when adjusted for clinical covariates. Surprisingly, among HPV-negative cases, a gene signature for HPV status was predictive of survival, even after adjustment for clinical covariates. Across the whole series, several gene signatures representing HPV and microsatellite instability remained significant in multivariate analysis. However, quality control and independent validation remain to be performed to add prognostic information above recently improved clinico-pathological variables

Receptor activity-modifying proteins 2 and 3 generate adrenomedullin receptor subtypes with distinct molecular properties

Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM1 and AM2 receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins (RAMP) 2 and 3, respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMPs 2 and 3 on the activation and conformation of the CLR subunit of AM receptors we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors and determined the effects on cAMP signalling. Sixteen CLR mutations had differential effects between the AM1 and AM2 receptors. Accompanying this, independent molecular modelling of the full-length AM-bound AM1 and AM2 receptors predicted differences in the binding pocket, and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function

Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse xenografts.

Inhibition of vascular endothelial growth factor increases response rates to chemotherapy and progression-free survival in glioblastoma. However, resistance invariably occurs, prompting the urgent need for identification of synergizing agents. One possible strategy is to understand tumor adaptation to microenvironmental changes induced by antiangiogenic drugs and test agents that exploit this process. We used an in vivo glioblastoma-derived xenograft model of tumor escape in presence of continuous treatment with bevacizumab. U87-MG or U118-MG cells were subcutaneously implanted into either BALB/c SCID or athymic nude mice. Bevacizumab was given by intraperitoneal injection every 3 days (2.5 mg/kg/dose) and/or dichloroacetate (DCA) was administered by oral gavage twice daily (50 mg/kg/dose) when tumor volumes reached 0.3 cm(3) and continued until tumors reached approximately 1.5-2.0 cm(3). Microarray analysis of resistant U87 tumors revealed coordinated changes at the level of metabolic genes, in particular, a widening gap between glycolysis and mitochondrial respiration. There was a highly significant difference between U87-MG-implanted athymic nude mice 1 week after drug treatment. By 2 weeks of treatment, bevacizumab and DCA together dramatically blocked tumor growth compared to either drug alone. Similar results were seen in athymic nude mice implanted with U118-MG cells. We demonstrate for the first time that reversal of the bevacizumab-induced shift in metabolism using DCA is detrimental to neoplastic growth in vivo. As DCA is viewed as a promising agent targeting tumor metabolism, our data establish the timely proof of concept that combining it with antiangiogenic therapy represents a potent antineoplastic strategy

Wolbachia Prophage DNA Adenine Methyltransferase Genes in Different Drosophila-Wolbachia Associations

Wolbachia is an obligatory intracellular bacterium which often manipulates the reproduction of its insect and isopod hosts. In contrast, Wolbachia is an essential symbiont in filarial nematodes. Lately, Wolbachia has been implicated in genomic imprinting of host DNA through cytosine methylation. The importance of DNA methylation in cell fate and biology calls for in depth studing of putative methylation-related genes. We present a molecular and phylogenetic analysis of a putative DNA adenine methyltransferase encoded by a prophage in the Wolbachia genome. Two slightly different copies of the gene, met1 and met2, exhibit a different distribution over various Wolbachia strains. The met2 gene is present in the majority of strains, in wAu, however, it contains a frameshift caused by a 2 bp deletion. Phylogenetic analysis of the met2 DNA sequences suggests a long association of the gene with the Wolbachia host strains. In addition, our analysis provides evidence for previously unnoticed multiple infections, the detection of which is critical for the molecular elucidation of modification and/or rescue mechanism of cytoplasmic incompatibility

The integration of occlusion and disparity information for judging depth in autism spectrum disorder

In autism spectrum disorder (ASD), atypical integration of visual depth cues may be due to flattened perceptual priors or selective fusion. The current study attempts to disentangle these explanations by psychophysically assessing within-modality integration of ordinal (occlusion) and metric (disparity) depth cues while accounting for sensitivity to stereoscopic information. Participants included 22 individuals with ASD and 23 typically developing matched controls. Although adults with ASD were found to have significantly poorer stereoacuity, they were still able to automatically integrate conflicting depth cues, lending support to the idea that priors are intact in ASD. However, dissimilarities in response speed variability between the ASD and TD groups suggests that there may be differences in the perceptual decision-making aspect of the task