A novel ATP1A2 mutation in a patient with hypokalaemic periodic paralysis and CNS symptoms

Hypokalaemic periodic paralysis is a rare genetic neuromuscular disease characterized by episodes of skeletal muscle paralysis associated with low serum potassium. Muscle fibre inexcitability during attacks of paralysis is due to an aberrant depolarizing leak current through mutant voltage sensing domains of either the sarcolemmal voltage-gated calcium or sodium channel. We report a child with hypokalaemic periodic paralysis and CNS involvement, including seizures, but without mutations in the known periodic paralysis genes. We identified a novel heterozygous de novo missense mutation in the ATP1A2 gene encoding the α2 subunit of the Na+/K+-ATPase that is abundantly expressed in skeletal muscle and in brain astrocytes. Pump activity is crucial for Na+ and K+ homeostasis following sustained muscle or neuronal activity and its dysfunction is linked to the CNS disorders hemiplegic migraine and alternating hemiplegia of childhood, but muscle dysfunction has not been reported. Electrophysiological measurements of mutant pump activity in Xenopus oocytes revealed lower turnover rates in physiological extracellular K+ and an anomalous inward leak current in hypokalaemic conditions, predicted to lead to muscle depolarization. Our data provide important evidence supporting a leak current as the major pathomechanism underlying hypokalaemic periodic paralysis and indicate ATP1A2 as a new hypokalaemic periodic paralysis gene

A model for the population of helium stars in the Galaxy I. Low-mass stars

By means of population synthesis we model the Galactic ensemble of helium stars. It is assumed that all helium stars are formed in binaries. Under this assumption, single helium stars are produced by the mergers of helium remnants of components of close binaries (mainly, by merging helium white dwarfs) and by disruption of binaries with helium components in supernovae explosions. The estimate of the total birthrate of helium stars in the Galaxy is 0.043 yr$^{-1}$, their total number is estimated as $4 \times 10^6$. The rate of binarity in the total sample is 76%. We construct a subsample of low-mass (M_{\rm He} \lesssim 2 \ms) helium stars limited by observational selection effects: stellar magnitude ($V_{\rm He} \leq 16$), ratio of stellar magnitudes of components in binaries ($V_{\rm He}\leq V_{\rm comp}$), lower limit of the semiamplitude of radial velocity that is necessary for discovery of binarity ($K_{min}=30$ km/s). The parameters of this ``observable'' sample are in satisfactory agreement with the parameters of the observed ensemble of sdB stars. In particular, in the selection-limited sample binarity rate is 58%. We analyze the relations between orbital periods and masses of helium stars and their companions in systems with different combinations of components. We expect that overwhelming majority ($\sim 90$%) of unobserved components in binary sdB stars are white dwarfs, predominantly, carbon-oxygen ones.Comment: 16 pages, 6 figures, submitted to Astronomy Reports, fig. 6 corrected, conclusions unchange

Transcriptomic analysis of the temporal host response to skin infestation with the ectoparasitic mite Psoroptes ovis

<p>Abstract</p> <p>Background</p> <p>Infestation of ovine skin with the ectoparasitic mite <it>Psoroptes ovis </it>results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Little is known regarding the mechanisms by which such a profound inflammatory response is instigated and to identify novel vaccine and drug targets a better understanding of the host-parasite relationship is essential. The main objective of this study was to perform a combined network and pathway analysis of the <it>in vivo </it>skin response to infestation with <it>P. ovis </it>to gain a clearer understanding of the mechanisms and signalling pathways involved.</p> <p>Results</p> <p>Infestation with <it>P. </it>ovis resulted in differential expression of 1,552 genes over a 24 hour time course. Clustering by peak gene expression enabled classification of genes into temporally related groupings. Network and pathway analysis of clusters identified key signalling pathways involved in the host response to infestation. The analysis implicated a number of genes with roles in allergy and inflammation, including pro-inflammatory cytokines (<it>IL1A, IL1B, IL6, IL8 </it>and <it>TNF</it>) and factors involved in immune cell activation and recruitment (<it>SELE, SELL, SELP, ICAM1, CSF2, CSF3, CCL2 </it>and <it>CXCL2</it>). The analysis also highlighted the influence of the transcription factors NF-kB and AP-1 in the early pro-inflammatory response, and demonstrated a bias towards a Th2 type immune response.</p> <p>Conclusions</p> <p>This study has provided novel insights into the signalling mechanisms leading to the development of a pro-inflammatory response in sheep scab, whilst providing crucial information regarding the nature of mite factors that may trigger this response. It has enabled the elucidation of the temporal patterns by which the immune system is regulated following exposure to <it>P. ovis</it>, providing novel insights into the mechanisms underlying lesion development. This study has improved our existing knowledge of the host response to <it>P. ovis</it>, including the identification of key parallels between sheep scab and other inflammatory skin disorders and the identification of potential targets for disease control.</p

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe

Measurement of D-s(+) product ion and nuclear modification factor in Pb-Pb collisions at root S-NN=2.76 TeV

Peer reviewe

Charged-particle multiplicities in proton-proton collisions at root s=0.9 to 8 TeV

A detailed study of pseudorapidity densities and multiplicity distributions of primary charged particles produced in proton-proton collisions, atv root s = 0.9, 2.36, 2.76, 7 and 8 TeV, in the pseudorapidity range vertical bar n vertical bar<2, was carried out using the ALICE detector. Measurements were obtained for three event classes: inelastic, non-single diffractive and events with at least one charged particle in the pseudorapidity interval vertical bar n vertical barPeer reviewe

Measurement of azimuthal correlations of D mesons with charged particles in pp collisions at √s=7 TeV and p-Pb collisions at √sNN=5.02 TeV

The azimuthal correlations of D mesons with charged particles were measured with the ALICE apparatus in pp collisions at root s = 7 TeV and p-Pb collisions at root sNN = 5.02 TeV at the Large Hadron Collider. D-0, D+, and D*+ mesons and their charge conjugates with transverse momentum 3 0.3 GeV/c. The yield of charged particles in the correlation peak induced by the jet containing the D meson and the peak width are compatible within uncertainties in the two collision systems. The data are described within uncertainties by Monte-Carlo simulations based on PYTHIA, POWHEG, and EPOS 3 event generators.Peer reviewe

Elliptic flow of electrons from heavy-flavour hadron decays at mid-rapidity in Pb-Pb collisions at root s(NN)=2.76 TeV

The elliptic flow of electrons from heavy-flavour hadron decays at mid-rapidity (|y| <0.7) is measured in Pb-Pb collisions at TeV with ALICE at the LHC. The particle azimuthal distribution with respect to the reaction plane can be parametrized with a Fourier expansion, where the second coefficient (v (2)) represents the elliptic flow. The v (2) coefficient of inclusive electrons is measured in three centrality classes (0-10%, 10-20% and 20-40%) with the event plane and the scalar product methods in the transverse momentum (p (T)) intervals 0.5-13 GeV/c and 0.5-8 GeV/c, respectively. After subtracting the background, mainly from photon conversions and Dalitz decays of neutral mesons, a positive v (2) of electrons from heavy-flavour hadron decays is observed in all centrality classes, with a maximum significance of 5.9 sigma in the interval 2 <p (T) <2.5 GeV/c in semi-central collisions (20-40%). The value of v (2) decreases towards more central collisions at low and intermediate p (T) (0.5 <p (T) <3 GeV/c). The v (2) of electrons from heavy-flavour hadron decays at mid-rapidity is found to be similar to the one of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4). The results are described within uncertainties by model calculations including substantial elastic interactions of heavy quarks with an expanding strongly-interacting medium.Peer reviewe

Coherent psi (2S) photo-production in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76TeV

We have performed the first measurement of the coherent psi(2S) photo-production cross section in ultraperipheral Pb-Pb collisions at the LHC. This charmonium excited state is reconstructed via the psi(2S) -> l(+)l(-) and ->(2S) -> J/psi pi(+)pi(-) decays, where the J/psi decays into two leptons. The analysis is based on an event sample corresponding to an integrated luminosity of about 22 mu b(-1). The cross section for coherent psi(2S) production in the rapidity interval -0.9 <y <0.9is d sigma(coh)(psi(2S))/dy = 0.83 +/- 0.19 (stat+syst) mb. The psi(2S) to J/psi coherent cross section ratio is 0.34(-0.07)(+0.08)(stat+syst). The obtained results are compared to predictions from theoretical models. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe