Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Internet Gaming Disorder in children and adolescents

The American Psychiatric Association recently included Internet gaming disorder (IGD) as a potential diagnosis, recommending that further study be conducted to help illuminate it more clearly. This paper is a summary of the review undertaken by the IGD Working Group as part of the 2015 National Academy of Sciences Sackler Colloquium on Digital Media and Developing Minds. By using measures based on or similar to the IGD definition, we found that prevalence rates range between ∼1% and 9%, depending on age, country, and other sample characteristics. The etiology of IGD is not well-understood at this time, although it appears that impulsiveness and high amounts of time gaming may be risk factors. Estimates for the length of time the disorder can last vary widely, but it is unclear why. Although the authors of several studies have demonstrated that IGD can be treated, no randomized controlled trials have yet been published, making any definitive statements about treatment impossible. IGD does, therefore, appear to be an area in which additional research is clearly needed. We discuss several of the critical questions that future research should address and provide recommendations for clinicians, policy makers, and educators on the basis of what we know at this time

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8)Peer reviewedPublisher PD

Comorbidades físicas e psicológicas antes e depois da cirurgia bariátrica : um estudo longitudinal

Introduction: Morbid obesity has multiple implications for psychological and physical health. Bariatric surgery has been selected as the treatment of choice for this chronic disease, despite the controversial impact of the surgery on psychosocial health. The objective of this study was to describe candidates for bariatric surgery and analyze changes in weight, psychopathology, personality, and health problems and complaints at 6- and 12- month follow-up assessments. Methods: Thirty obese patients (20 women and 10 men) with a mean age of 39.17±8.81 years were evaluated in different dimensions before surgery and 6 and 12 months after the procedure. Results: Six and 12 months after bariatric surgery, patients reported significant weight loss and a significant reduction in the number of health problems and complaints. The rates of self-reported psychopathology were low before surgery, and there were no statistically significant changes over time. The conscientiousness, extraversion, and agreeableness dimensions increased, but neuroticism and openness remained unchanged. All changes had a medium effect size. Conclusions: Our results suggest that patients experience significant health improvements and some positive personality changes after bariatric surgery. Even though these findings underscore the role of bariatric surgery as a relevant treatment for morbid obesity, more in-depth longitudinal studies are needed to elucidate the evolution of patients after the procedure.Introdução: A obesidade mórbida tem várias implicações para a saúde psicológica e física. A cirurgia bariátrica tem sido o tratamento de escolha para essa doença crônica, apesar da controvérsia sobre o impacto da cirurgia na saúde psicossocial. O objetivo deste estudo foi descrever candidatos a cirurgia bariátrica e analisar mudanças no peso, psicopatologia personalidade, problemas e queixas de saúde desses pacientes em avaliações realizadas 6 e 12 meses após a cirurgia. Métodos: Trinta pacientes obesos (20 mulheres e 10 homens) com idade média de 39,17±8,81 anos foram avaliados em diferentes dimensões antes da cirurgia e 6 e 12 meses após. Resultados: Aos 6 e 12 meses após a cirurgia bariátrica, os pacientes relataram significativa perda de peso e significativa redução no número de problemas e queixas de saúde. As taxas de psicopatologia autorrelatada foram baixas antes da cirurgia e não sofreram mudanças significativas com o tempo. As dimensões conscienciosidade, extroversão e agradabilidade aumentaram, mas o neuroticismo e a abertura permaneceram inalteradas. Todas as mudanças apresentaram um tamanho de efeito médio. Conclusões: Os nossos resultados sugerem que os pacientes experimentam melhoras significativas em saúde e algumas mudanças positivas de personalidade após a cirurgia bariátrica. Embora esses achados reforcem o papel da cirurgia bariátrica como um tratamento relevante para a obesidade mórbida, mais estudos longitudinais e aprofundados são necessários para elucidar a evolução dos pacientes após a realização do procedimento.(undefined

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

Jugular venous reflux and brain parenchyma volumes in elderly patients with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. RESULTS: JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR-positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). CONCLUSIONS: JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema