Role of the Mitochondrion in Programmed Necrosis

In contrast to the “programmed” nature of apoptosis and autophagy, necrotic cell death has always been believed to be a random, uncontrolled process that leads to the “accidental” death of the cell. This dogma, however, is being challenged and the concept of necrosis also being “programmed” is gaining ground. In particular, mitochondria appear to play a pivotal role in the mediation of programmed necrosis. The purpose of this review, therefore, is to appraise the current concepts regarding the signaling mechanisms of programmed necrosis, with specific attention to the contribution of mitochondria to this process

Regulation of neuronal excitability through pumilio-dependent control of a sodium channel gene

Dynamic changes in synaptic connectivity and strength, which occur during both embryonic development and learning, have the tendency to destabilize neural circuits. To overcome this, neurons have developed a diversity of homeostatic mechanisms to maintain firing within physiologically defined limits. In this study, we show that activity-dependent control of mRNA for a specific voltage-gated Na+ channel [encoded by paralytic (para)] contributes to the regulation of membrane excitability in Drosophila motoneurons. Quantification of para mRNA, by real-time reverse-transcription PCR, shows that levels are significantly decreased in CNSs in which synaptic excitation is elevated, whereas, conversely, they are significantly increased when synaptic vesicle release is blocked. Quantification of mRNA encoding the translational repressor pumilio (pum) reveals a reciprocal regulation to that seen for para. Pumilio is sufficient to influence para mRNA. Thus, para mRNA is significantly elevated in a loss-of-function allele of pum (pumbemused), whereas expression of a full-length pum transgene is sufficient to reduce para mRNA. In the absence of pum, increased synaptic excitation fails to reduce para mRNA, showing that Pum is also necessary for activity-dependent regulation of para mRNA. Analysis of voltage-gated Na+ current (INa) mediated by para in two identified motoneurons (termed aCC and RP2) reveals that removal of pum is sufficient to increase one of two separable INa components (persistent INa), whereas overexpression of a pum transgene is sufficient to suppress both components (transient and persistent). We show, through use of anemone toxin (ATX II), that alteration in persistent INa is sufficient to regulate membrane excitability in these two motoneurons

Ruling Out Possible Secondary Stars to Exoplanet Host Stars Using the CHARA Array

Of the over 450 exoplanets known to date, more than 420 of them have been discovered using radial velocity studies, a method that tells nothing about the inclination of the planet's orbit. Because it is more likely that the companion is a planetary-mass object in a moderate- to high-inclination orbit than a low-mass stellar object in a nearly face-on orbit, the secondary bodies are presumed to be planets. Interferometric observations allow us to inspect the angular diameter fit residuals to calibrated visibilities in order to rule out the possibility of a low-mass stellar companion in a very low-inclination orbit. We used the Center for High Angular Resolution Astronomy (CHARA) Array interferometer to observe 20 exoplanet host stars and considered five potential secondary spectral types: G5 V, K0 V, K5 V, M0 V, and M5 V. If a secondary star is present and is sufficiently bright, the effects of the added light will appear in interferometric observations where the planet will not. All secondary types could be eliminated from consideration for 7 host stars and no secondary stars of any spectral type could be ruled out for 7 more. The remaining 6 host stars showed a range of possible secondary types.Comment: Accepted for publication in the Astronomical Journa

Evidence for Coexistence of Bulk Superconductivity and Itinerant Antiferromagnetism in the Heavy Fermion System CeCo(In1−x_{1-x}Cdx_x)5_5

In the generic phase diagram of heavy fermion systems, tuning an external parameter such as hydrostatic or chemical pressure modifies the superconducting transition temperature. The superconducting phase forms a dome in the temperature-tuning parameter phase diagram, which is associated with a maximum of the superconducting pairing interaction. Proximity to antiferromagnetism suggests a relation between the disappearance of antiferromagnetic order and superconductivity. We combine muon spin rotation, neutron scattering, and x-ray absorption spectroscopy techniques to gain access to the magnetic and electronic structure of CeCo(In$_{1-x}$Cd$_x$)$_5$ at different time scales. Different magnetic structures are obtained that indicate a magnetic order of itinerant character, coexisting with bulk superconductivity. The suppression of the antiferromagnetic order appears to be driven by a modification of the bandwidth/carrier concentration, implying that the electronic structure and consequently the interplay of superconductivity and magnetism is strongly affected by hydrostatic and chemical pressure.Comment: Article + Supplementary information 33 pages, 13 figure

Understanding the independent dancer: roles, development and success

Little research has been published about the varied role of the independent dancer. The aim of this study was to provide insight into the work independent dancers undertake and how their careers change over time. Semi-structured interviews were conducted with 14 independent dancers. Content analysis revealed that the dancers had multifaceted careers that relied on both formal and informal activities, and varied according to three distinct stages (early, middle, late). The experiences reported by the dancers indicated that the realities of the independent dancer's role are not sufficiently recognised or supported within the industry

Prevalence of constipation in people with intellectual disabilities:a systematic review

Background. Constipation can lead to serious health issues and death. This systematic review summarises international research pertaining to the prevalence of constipation in people with intellectual disability. Method. Studies published from 1990 to January 2016 were identified using Medline, Cinahl, PsycINFO, Web of Science, email requests, and cross-citations. Studies were reviewed narratively. Results. 31 studies were identified. Constipation rates of 50% or more were reported in 14 studies; 21 studies reported rates over 33%. Based on the most representative study, over 25% of people with intellectual disability received a repeat prescription for laxatives in one year, compared to 0.1% of people without intellectual disability. Constipation was more common in those with cerebral palsy and profound intellectual disability, and associated with immobility but not age. Conclusion. Constipation is a significant issue for people with intellectual disability across the life course and should be actively considered as a diagnosis in this population

Quantum Coherence at Low Temperatures in Mesoscopic Systems: Effect of Disorder

We study the disorder dependence of the phase coherence time of quasi one-dimensional wires and two-dimensional (2D) Hall bars fabricated from a high mobility GaAs/AlGaAs heterostructure. Using an original ion implantation technique, we can tune the intrinsic disorder felt by the 2D electron gas and continuously vary the system from the semi-ballistic regime to the localized one. In the diffusive regime, the phase coherence time follows a power law as a function of diffusion coefficient as expected in the Fermi liquid theory, without any sign of low temperature saturation. Surprisingly, in the semi-ballistic regime, it becomes independent of the diffusion coefficient. In the strongly localized regime we find a diverging phase coherence time with decreasing temperature, however, with a smaller exponent compared to the weakly localized regime.Comment: 21 pages, 30 figure

Obesity in British children with and without intellectual disability:cohort study

Background Reducing the prevalence of and inequities in the distribution of child obesity will require developing interventions that are sensitive to the situation of ‘high risk’ groups of children. Children with intellectual disability appear to be one such group. We aimed to estimate the prevalence of obesity in children with and without intellectual disability in a longitudinal representative sample of British children and identify risk factors associated with obesity at age 11. Methods Information was collected on a nationally representative sample of over 18,000 at ages 9 months, 3, 5, 7 and 11 years. We used UK 1990 gender-specific growth reference charts and the LMS Growth programme to identify age and gender-specific overweight and obesity BMI thresholds for each child at ages five, seven and eleven years. Results Children with intellectual disabilities were significantly more likely than other children to be obese at ages five (OR=1.32[1.03-1.68]), seven (OR=1.39[1.05-1.83]) and eleven (OR=1.68[1.39-2.03]). At ages five and seven increased risk of obesity among children with intellectual disabilities was only apparent among boys. Among children with intellectual disability risk of obesity at age eleven was associated with persistent maternal obesity, maternal education, child ethnicity and being bullied at age five. Conclusions Children with intellectual disability are a high-risk group for the development of obesity, accounting for 5-6% of all obese children. Interventions to reduce the prevalence and inequities in the distribution of child obesity will need to take account of the specific situation of this group of children