Sequential bottlenecks drive viral evolution in early acute Hepatitis C virus infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection

Neutral H density at the termination shock: a consolidation of recent results

We discuss a consolidation of determinations of the density of neutral interstellar H at the nose of the termination shock carried out with the use of various data sets, techniques, and modeling approaches. In particular, we focus on the determination of this density based on observations of H pickup ions on Ulysses during its aphelion passage through the ecliptic plane. We discuss in greater detail a novel method of determination of the density from these measurements and review the results from its application to actual data. The H density at TS derived from this analysis is equal to 0.087 \pm 0.022 cm-3, and when all relevant determinations are taken into account, the consolidated density is obtained at 0.09 \pm 0.022 cm-3. The density of H in CHISM based on literature values of filtration factor is then calculated at 0.16 \pm 0.04 cm-3.Comment: Submitted to Space Science Review

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197

Solar parameters for modeling interplanetary background

The goal of the Fully Online Datacenter of Ultraviolet Emissions (FONDUE) Working Team of the International Space Science Institute in Bern, Switzerland, was to establish a common calibration of various UV and EUV heliospheric observations, both spectroscopic and photometric. Realization of this goal required an up-to-date model of spatial distribution of neutral interstellar hydrogen in the heliosphere, and to that end, a credible model of the radiation pressure and ionization processes was needed. This chapter describes the solar factors shaping the distribution of neutral interstellar H in the heliosphere. Presented are the solar Lyman-alpha flux and the solar Lyman-alpha resonant radiation pressure force acting on neutral H atoms in the heliosphere, solar EUV radiation and the photoionization of heliospheric hydrogen, and their evolution in time and the still hypothetical variation with heliolatitude. Further, solar wind and its evolution with solar activity is presented in the context of the charge exchange ionization of heliospheric hydrogen, and in the context of dynamic pressure variations. Also the electron ionization and its variation with time, heliolatitude, and solar distance is presented. After a review of all of those topics, we present an interim model of solar wind and the other solar factors based on up-to-date in situ and remote sensing observations of solar wind. Results of this effort will further be utilised to improve on the model of solar wind evolution, which will be an invaluable asset in all heliospheric measurements, including, among others, the observations of Energetic Neutral Atoms by the Interstellar Boundary Explorer (IBEX).Comment: Chapter 2 in the planned "Cross-Calibration of Past and Present Far UV Spectra of Solar System Objects and the Heliosphere", ISSI Scientific Report No 12, ed. R.M. Bonnet, E. Quemerais, M. Snow, Springe

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Increase in oxygen consumption after albuterol inhalation in ventilated infants and children

Item does not contain fulltextOBJECTIVE: To determine if inhaled albuterol (salbutamol) increases oxygen consumption (V'O2) in children and, if so, the duration of this effect. DESIGN: Oxygen consumption was measured by indirect calorimetry using the Argon dilution technique with a respiratory mass spectrometer. After measurement of baseline values, albuterol was administered and subsequent measurements were performed at 10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. SETTING: Multidisciplinary PICU in a university teaching hospital. PATIENTS: Eleven intubated infants and children (five girls, six boys) with a mean age of 20 months (range, 1 mo to 8 yr) and a mean weight of 10.7 kg (range, 3.1-23 kg) who required therapeutic albuterol inhalations. INTERVENTION: Nine hundred micrograms of albuterol (10 puffs) was administered by a metered-dose inhaler into a spacer through the inspiratory arm of the ventilator circuit near to the patient, during 10 mechanically assisted breaths. MEASUREMENTS AND MAIN RESULTS: All children showed an increase in V'O2 within 10 minutes (mean increase 48.6%). The increased V'O2 was still elevated (42.3% above baseline) at 1 hour, but 3 hours after albuterol inhalation, the V'O2 was back to baseline in all patients. Heart rate increased significantly at 10 minutes, 1 hour, and 2 hours after inhalation. CONCLUSION: There is a large increase in V'O2 after albuterol inhalation. This effect lasts up to 3 hours

Some approximants in operator algebras.

In this paper we extend to C*-algebras and to von Neumann algebras some results on approximants that have previously been found in the context of (H) and of the von Neumann-Schatten classesC p , 1⩽ p <∞. We obtain results concerning positive approximants, unitary and partially isometric approximants and commutator approximants; and we study paranormality. Our main tools are the Gelfand-naimark Theorem and Berntzen’s results on normal spectral approximation