Context specificity of post-error and post-conflict cognitive control adjustments

There has been accumulating evidence that cognitive control can be adaptively regulated by monitoring for processing conflict as an index of online control demands. However, it is not yet known whether top-down control mechanisms respond to processing conflict in a manner specific to the operative task context or confer a more generalized benefit. While previous studies have examined the taskset-specificity of conflict adaptation effects, yielding inconsistent results, controlrelated performance adjustments following errors have been largely overlooked. This gap in the literature underscores recent debate as to whether post-error performance represents a strategic, control-mediated mechanism or a nonstrategic consequence of attentional orienting. In the present study, evidence of generalized control following both high conflict correct trials and errors was explored in a task-switching paradigm. Conflict adaptation effects were not found to generalize across tasksets, despite a shared response set. In contrast, post-error slowing effects were found to extend to the inactive taskset and were predictive of enhanced post-error accuracy. In addition, post-error performance adjustments were found to persist for several trials and across multiple task switches, a finding inconsistent with attentional orienting accounts of post-error slowing. These findings indicate that error-related control adjustments confer a generalized performance benefit and suggest dissociable mechanisms of post-conflict and post-error control. © 2014 Forster, Cho

Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

<p>Abstract</p> <p>Background</p> <p>Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions.</p> <p>Results</p> <p>Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways). Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods.</p> <p>Conclusions</p> <p>Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.</p

Expression of miRNAs miR-133b and miR-206 in the Il17a/f Locus Is Co-Regulated with IL-17 Production in αβ and γδ T Cells

Differentiation of T helper 17 cells (Th17) is a multistep process that involves the cytokines IL-6, TGF-β, and IL-23 as well as IL-1β, IL-21, and TNF-α. Thereby, robust induction of the capacity to produce IL-17 involves epigenetic modifications of the syntenic Il17a/f locus. Using inbred mouse strains, we identified co-regulation of gene transcription at the Il17a/f locus with the nearby microRNAs miR-133b and miR-206 that are clustered approximately 45 kb upstream of Il17a/f. Expression of these microRNAs was specific for Th17 as compared to other CD4+ T cell subsets and this was equally valid for in vitro polarized and ex vivo derived cells. From all factors analyzed, IL-23 was the most important cytokine for the in vitro induction of miR-133b and miR-206 in naive CD4+ T cells of wild type mice. However, analysis of IL-23R deficient mice revealed that IL-23R signaling was not essential for the induction of miR-133b and miR-206. Importantly, we found a similar co-regulation in CCR6+ and other γδ T cell subsets that are predisposed to production of IL-17. Taken together, we discovered a novel feature of T cell differentiation towards an IL-17-producing phenotype that is shared between αβ and γδ T cells. Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions

Transient and sustained incentive effects on electrophysiological indices of cognitive control in younger and older adults

Preparing for upcoming events, separating task-relevant from task-irrelevant information and efficiently responding to stimuli all require cognitive control. The adaptive recruitment of cognitive control depends on activity in the dopaminergic reward system as well as the frontoparietal control network. In healthy aging, dopaminergic neuromodulation is reduced, resulting in altered incentive-based recruitment of control mechanisms. In the present study, younger adults (18–28 years) and healthy older adults (66–89 years) completed an incentivized flanker task that included gain, loss, and neutral trials. Event-related potentials (ERPs) were recorded at the time of incentive cue and target presentation. We examined the contingent negative variation (CNV), implicated in stimulus anticipation and response preparation, as well as the P3, which is involved in the evaluation of visual stimuli. Both younger and older adults showed transient incentive-based modulation of CNV. Critically, cue-locked and target-locked P3s were influenced by transient and sustained effects of incentives in younger adults, while such modulation was limited to a sustained effect of gain incentives on cue-P3 in older adults. Overall, these findings are in line with an age-related reduction in the flexible recruitment of preparatory and target-related cognitive control processes in the presence of motivational incentives

Large, rare chromosomal deletions associated with severe early-onset obesity

Obesity is a highly heritable and genetically heterogeneous disorder1. Here we investigated the contribution of copy number variation to obesity in 300 Caucasian patients with severe early-onset obesity, 143 of whom also had developmental delay. Large (>500 kilobases), rare (<1%) deletions were significantly enriched in patients compared to 7,366 controls (P < 0.001). We identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls. We identified five patients with overlapping deletions on chromosome 16p11.2 that were found in 2 out of 7,366 controls (P < 5 × 10(−5)). In three patients the deletion co-segregated with severe obesity. Two patients harboured a larger de novo 16p11.2 deletion, extending through a 593-kilobase region previously associated with autism2-4 and mental retardation5; both of these patients had mild developmental delay in addition to severe obesity. In an independent sample of 1,062 patients with severe obesity alone, the smaller 16p11.2 deletion was found in an additional two patients. All 16p11.2 deletions encompass several genes but include SH2B1, which is known to be involved in leptin and insulin signalling6. Deletion carriers exhibited hyperphagia and severe insulin resistance disproportionate for the degree of obesity. We show that copy number variation contributes significantly to the genetic architecture of human obesity