Embodied Models and Neurorobotics

Neuroscience has become a very broad field indeed: each year around 30,000 researchers and students from around the ... We trace a path from neuron to cognition via computational neuroscience, but what is computational neuroscience

eIF2B bodies and their role in the integrated stress response

Eukaryotic initiation factor 2 (eIF2) is a G protein comprised of 3 subunits (α, β and γ) that is critical for translation. It is tightly regulated in the integrated stress response (ISR) via the phosphorylation of its α subunit following the induction of cellular stress. In its phosphorylated form eIF2α inhibits the guanine nucleotide exchange factor (GEF) eukaryotic initiation factor 2B (eIF2B), resulting in the attenuation of global protein synthesis. eIF2B is a multisubunit protein comprised of regulatory and catalytic subunits. The catalytic subunits are responsible for the GEF activity whereas the regulatory subunits mediate inhibition by phosphorylated eIF2α. Through studying the localisation of eIF2B subunits, cytoplasmic eIF2B bodies were identified in mammalian cells. A relationship between body size and the eIF2B subunits localising to them exists; larger bodies contain all subunits and smaller bodies contain predominantly catalytic subunits. eIF2 localises to eIF2B bodies and moves through these bodies in a manner that correlates with eIF2B GEF activity. Upon the induction of cellular stress phosphorylated eIF2α localises predominately to larger eIF2B bodies which contain regulatory subunits and a decrease in the movement of eIF2 through these bodies is observed. Interestingly, drugs that inhibit the ISR can rescue the movement of eIF2 through these eIF2B bodies, in a manner that correlates to cellular levels of phosphorylated eIF2α. In contrast, smaller eIF2B bodies, which contain predominately catalytic subunits, show increased movement of eIF2 during cellular stress. This increase in movement is accompanied by an increase in the localisation of eIF2Bδ to these bodies, suggesting the formation of a novel eIF2B subcomplex. This response is mimicked by ISR-inhibiting drugs, providing insight into their potential mechanisms of action. This study provides the first evidence that the composition and function of mammalian eIF2B bodies is regulated by the ISR and the drugs that control it

Intimate Partner Violence: The Impact of the Relationship between Perpetrators and Children who Witness Violence

The issue of the father—child relationship has been greatly ignored in the domestic violence research literature. This study investigated whether intimate partner violence (IPV) perpetrated by biological fathers resulted in higher levels of posttraumatic stress symptoms and behavior problems than violence perpetrated by nonbiological fathers and whether children who witnessed violence perpetrated by multiple father figures had increased levels of posttraumatic stress disorder and behavioral symptoms. Eighty mothers who experienced domestic incidents completed the Child Behavior Checklist (CBCL) and the University of California at Los Angeles Posttraumatic Stress Disorder Reaction Index (PTSD-RI) for their children aged 2 to 18. Children with multiple violent father figures had significantly more symptoms on the CBCL than children in the other two research groups while controlling for maternal symptoms and trauma history. There were no significant differences between the biological and nonbiological father groups or among the three groups on the PTSD-RI

European cardiomyopathy pilot registry: EURObservational research programme of the European society of cardiology

Aims: Cardiomyopathies are a heterogeneous group of disorders associated with premature death due to ventricular arrhythmia or heart failure. The purpose of this study was to examine the characteristics of patients enrolled in the pilot phase of the EURObservational Research Programme (EORP) cardiomyopathy registry. Methods and results: Between 1 December 2012 and 30 November 2013, four cardiomyopathy phenotypes were studied: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). Twenty-seven centres in 12 countries participated; 1115 patients were enrolled. The commonest cardiomyopathy was HCM (n = 681), followed by DCM (n = 346), ARVC (n = 59), and RCM (n = 29); 423 patients (46.4% of those reported) had familial disease; and 56 (5.0%) had rare disease phenocopies. Median age at enrolment and diagnosis was 54 [interquartile range (IQR), 42-64] and 46 years (IQR, 32-58), respectively; fewer patients with ARVC and more with RCM were diagnosed in the upper age quartile (P, 0.0001). There was a male predominance for all cardiomyopathies except RCM (P = 0.0023). Most patients were in New York Heart Association functional class I (n = 813) at enrolment; 139 (12.5%) reported syncope, most frequently in ARVC (P = 0.0009). Five hundred and seven (45.5%) patients underwent cardiac magnetic resonance imaging, 117 (10.6%) endomyocardial biopsy, and 462 (41.4%) genetic testing with a causative mutation reported in 236 individuals (51.1%). 1026 patients (92.0%) were receiving drug therapy; 316 (28.3%) had received an implantable cardioverter defibrillator (highest proportion in ARVC, P, 0.0001). Conclusion: This pilot study shows that services for patients with cardiomyopathy are complex, requiring access to a large range of invasive and non-invasive investigations and involvement of multidisciplinary teams. Treatment regimens are equally multifaceted and show that patients are likely to need long-term follow-up in close liaison with expert centres. © The Author 2015