Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

Rhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral nervous system is poorly defined. Here, we used mouse models of RCDP and analyzed the consequence of plasmalogen deficiency in peripheral nerves. We determined that plasmalogens are crucial for Schwann cell development and differentiation and that plasmalogen defects impaired radial sorting, myelination, and myelin structure. Plasmalogen insufficiency resulted in defective protein kinase B (AKT) phosphorylation and subsequent signaling, causing overt activation of glycogen synthase kinase 3β (GSK3β) in nerves of mutant mice. Treatment with GSK3β inhibitors, lithium, or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) restored Schwann cell defects, effectively bypassing plasmalogen deficiency. Our results demonstrate the requirement of plasmalogens for the correct and timely differentiation of Schwann cells and for the process of myelination. In addition, these studies identify a mechanism by which the lack of a membrane phospholipid causes neuropathology, implicating plasmalogens as regulators of membrane and cell signaling.We thank Paula Sampaio for microscopy support, Paula Magalhdes for genotyping, and Isabel Carvalho, Sofia Lamas, and Fatima Martins for excellent animal care. We are grateful to P. Brophy (University of Edinburgh) for the DRP2 antibody and to M. Baes (K.U. Leuven) for providing the Gnpat mouse strain. This work was funded by the Research Foundation of the European Leukodystrophy Association (ELA 2008-009C4, ELA 2010-042C5), by FEDER Funds through the Operational Competitiveness Program - COMPETE, and by national funds through the FCT - Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-015970 (PTDS/SAU-ORG/112406/2009). P. Brites is an FCT Investigator, and T. Ferreira da Silva was supported by the FCT (SFRH/BD/88160/2012)

Origin of the low-mass electron pair excess in light nucleus-nucleus collisions

We report measurements of electron pair production in elementary p+p and d+p reactions at 1.25 GeV/u with the HADES spectrometer. For the first time, the electron pairs were reconstructed for n+p reactions by detecting the proton spectator from the deuteron breakup. We find that the yield of electron pairs with invariant mass Me+e- > 0.15 GeV/c2 is about an order of magnitude larger in n+p reactions as compared to p+p. A comparison to model calculations demonstrates that the production mechanism is not sufficiently described yet. The electron pair spectra measured in C+C reactions are compatible with a superposition of elementary n+p and p+p collisions, leaving little room for additional electron pair sources in such light collision systems.Comment: 11 pages, 2 figures, \usepackage{epsfig

Study of dielectron production in C+C collisions at 1 AGeV

The emission of e+e- pairs from C+C collisions at an incident energy of 1 GeV per nucleon has been investigated. The measured production probabilities, spanning from the pi0-Dalitz to the rho/omega! invariant-mass region, display a strong excess above the cocktail of standard hadronic sources. The bombarding-energy dependence of this excess is found to scale like pion production, rather than like eta production. The data are in good agreement with results obtained in the former DLS experiment.Comment: submitted to Physics Letters

Prediction of the in-flight radiation patterns of the Planck telescope

This paper summarises the work done over the last few years on the prediction of the RF performance of the Planck telescope, which was done initially to support the design phase, and later to assess compliance to specifications and to infer the in-flight performance of the telescope once in its operational orbit

Functional Anatomy of the Female Pelvic Floor

The anatomic structures in the female that prevent incontinence and genital organ prolapse on increases in abdominal pressure during daily activities include sphincteric and supportive systems. In the urethra, the action of the vesical neck and urethral sphincteric mechanisms maintains urethral closure pressure above bladder pressure. Decreases in the number of striated muscle fibers of the sphincter occur with age and parity. A supportive hammock under the urethra and vesical neck provides a firm backstop against which the urethra is compressed during increases in abdominal pressure to maintain urethral closure pressures above the rapidly increasing bladder pressure. This supporting layer consists of the anterior vaginal wall and the connective tissue that attaches it to the pelvic bones through the pubovaginal portion of the levator ani muscle, and the uterosacral and cardinal ligaments comprising the tendinous arch of the pelvic fascia. At rest the levator ani maintains closure of the urogenital hiatus. They are additionally recruited to maintain hiatal closure in the face of inertial loads related to visceral accelerations as well as abdominal pressurization in daily activities involving recruitment of the abdominal wall musculature and diaphragm. Vaginal birth is associated with an increased risk of levator ani defects, as well as genital organ prolapse and urinary incontinence. Computer models indicate that vaginal birth places the levator ani under tissue stretch ratios of up to 3.3 and the pudendal nerve under strains of up to 33%, respectively. Research is needed to better identify the pathomechanics of these conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72597/1/annals.1389.034.pd

School-based prevention for adolescent Internet addiction: prevention is the key. A systematic literature review

Adolescents’ media use represents a normative need for information, communication, recreation and functionality, yet problematic Internet use has increased. Given the arguably alarming prevalence rates worldwide and the increasingly problematic use of gaming and social media, the need for an integration of prevention efforts appears to be timely. The aim of this systematic literature review is (i) to identify school-based prevention programmes or protocols for Internet Addiction targeting adolescents within the school context and to examine the programmes’ effectiveness, and (ii) to highlight strengths, limitations, and best practices to inform the design of new initiatives, by capitalizing on these studies’ recommendations. The findings of the reviewed studies to date presented mixed outcomes and are in need of further empirical evidence. The current review identified the following needs to be addressed in future designs to: (i) define the clinical status of Internet Addiction more precisely, (ii) use more current psychometrically robust assessment tools for the measurement of effectiveness (based on the most recent empirical developments), (iii) reconsider the main outcome of Internet time reduction as it appears to be problematic, (iv) build methodologically sound evidence-based prevention programmes, (v) focus on skill enhancement and the use of protective and harm-reducing factors, and (vi) include IA as one of the risk behaviours in multi-risk behaviour interventions. These appear to be crucial factors in addressing future research designs and the formulation of new prevention initiatives. Validated findings could then inform promising strategies for IA and gaming prevention in public policy and education

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)