Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo

GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron diseases. Homozygous gle1−/− mutant zebrafish display various aspects of LCCS, showing severe developmental abnormalities including motor neuron arborization defects and embryonic lethality. A previous gene expression study on spinal cord from LCCS fetuses indicated that oligodendrocyte dysfunction may be an important factor in LCCS. We therefore set out to investigate the development of myelinating glia in gle1−/− mutant zebrafish embryos. While expression of myelin basic protein (mbp) in hindbrain oligodendrocytes appeared relatively normal, our studies revealed a prominent defect in Schwann cell precursor proliferation and differentiation in the posterior lateral line nerve. Other genes mutated in LCCS have important roles in Schwann cell development, thereby suggesting that Schwann cell deficits may be a common factor in LCCS pathogenesis. These findings illustrate the potential importance of glial cells such as myelinating Schwann cells in motor neuron diseases linked to RNA processing defects

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

Association between exhaled nitric oxide, ambient air pollution and respiratory health in school children

Association between exhaled nitric oxide, ambient air pollution and respiratory health in school children. Fischer PH, Steerenberg PA, Snelder JD, van Loveren H, van Amsterdam JG. Laboratory of Exposure Assessment and Environmental Epidemiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. OBJECTIVES: The aim of the study was to investigate whether the level of exhaled nitric oxide (eNO) provides a more sensitive measure to assess adverse pulmonary effects of air pollution than conventional lung function indices. METHOD: The non-selected cohort studied consisted of 68 children (aged 10-11 years) living in an urban environment. For 7 weeks respiratory complaints were reported daily by these children in a diary, and lung function measures and eNO levels were determined in the children once a week on days with various level of air pollution. RESULTS: During the study the increase in the levels of the various air pollutants was positively associated with eNO (6% to 31% increase; P<0.05) but not with lung function measures. In contrast to the lung function measures, the prevalence of respiratory symptoms such as "sore throat", "runny nose", "having a cold", and "sick at home" were positively associated with the level of eNO measured in the following week. CONCLUSIONS: Though clinically very meaningful, functional pulmonary measures appear to be too course to detect relatively mild clinical symptoms in response to exposure to air pollution. In an epidemiological setting the increase in eNO may represent a more suitable measure to assess such adverse effects

Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder a randomized clinical trial

IMPORTANCE Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone. OBJECTIVE To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD). Copyright 2014 American Medical Association. All rights reserved