Stakeholder Forum activities

The Deliverable 5.4.2 (Stakeholder Forums activities) is conceived as a report to inform about activities carried out in the Stakeholder Fora. It is conceived as a dynamic document, following progresses in the Stakeholder Forum organization and set up and reporting relevant achievements. It is substantially divided into three sections: The first one, represented by the Executive Summary and the Introduction, is not expected to change during the project life, at least in its core elements; The second one, represented by activities carried out in the Stakeholder Fora (Chapter 1), as general information on specific events, summarizing relevant activities performed in specific events, is supposed to change and be enlarged during the project life, so to provide updates on the activities carried out in Task 5.4.2 – Stakeholder Forum Activities. Next Actions: in Chapter 2 an overview is done on the activities planned to organize the next Stakeholder Fora. Annex 1 presents the Dissemination material to be presented at the General Stakeholder Fora. Annex 2 shows the Dissemination material presented during the TeleFOT First General Stakeholder Forum

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

Open Access via PMC2649417Peer reviewedPublisher PD

ALMA images the many faces of the NGC 1068 torus and its surroundings

Aims. We investigate the fueling and the feedback of nuclear activity in the nearby (D = 14 Mpc) Seyfert 2 barred galaxy NGC 1068 by studying the distribution and kinematics of molecular gas in the torus and its connections to the host galaxy disk. Methods.We used the Atacama Large Millimeter Array (ALMA ) to image the emission of a set of molecular gas tracers in the circumnuclear disk (CND) and the torus of the galaxy using the CO(2-1), CO(3-2), and HCO+(4-3) lines and their underlying continuum emission with high spatial resolutions (0:0300 0:0900 \u27 26 pc). These transitions, which span a wide range of physical conditions of molecular gas (n(H2) 103107 cm3), are instrumental in revealing the density radial stratification and the complex kinematics of the gas in the torus and its surroundings. Results. The ALMA images resolve the CND as an asymmetric ringed disk of D \u27 400 pc in size and \u271:4 108 M in mass. The CND shows a marked deficit of molecular gas in its central \u27130 pc region. The inner edge of the ring is associated with the presence of edge-brightened arcs of NIR polarized emission, which are identified with the current working surface of the ionized wind of the active galactic nucleus (AGN). ALMA proves the existence of an elongated molecular disk/torus in NGC 1068 of Mgas torus \u27 3 105 M, which extends over a large range of spatial scales D \u27 1030 pc around the central engine. The new observations evidence the density radial stratification of the torus: the HCO+(4-3) torus, with a full size DHCO+(43) = 11 0:6 pc, is a factor of between two and three smaller than its CO(2-1) and CO(3-2) counterparts, which have full sizes of DCO(32) = 26 0:6 pc and DCO(21) = 28 0:6 pc, respectively. This result brings into light the many faces of the molecular torus. The torus is connected to the CND through a network of molecular gas streamers detected inside the CND ring. The kinematics of molecular gas show strong departures from circular motions in the torus, the gas streamers, and the CND ring. These velocity field distortions are interconnected and are part of a 3D outflow that reflects the eects of AGN feedback on the kinematics of molecular gas across a wide range of spatial scales around the central engine. In particular, we estimate through modeling that a significant fraction of the gas inside the torus (\u270:40:6 Mgas torus) and a comparable amount of mass along the gas streamers are outflowing. However, the bulk of the mass, momentum, and energy of the molecular outflow of NGC 1068 is contained at larger radii in the CND region, where the AGN wind and the radio jet are currently pushing the gas assembled at the Inner Lindblad Resonance (ILR) ring of the nuclear stellar bar. Conclusions. In our favored scenario a wide-angle AGN wind launched from the accretion disk of NGC1068 is currently impacting a sizable fraction of the gas inside the torus. However, a large gas reservoir (\u271:21:8 105 M), which lies close to the equatorial plane of the torus, remains unaected by the feedback of the AGN wind and can therefore continue fueling the AGN for at least \u2714 Myr. Nevertheless, AGN fueling currently seems thwarted on intermediate scales (15 pc r 50 pc)

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Clostridium difficile infection among hospitalized HIV-infected individuals: epidemiology and risk factors: results from a case-control study (2002-2013).

BACKGROUND: HIV infection is a risk factor for Clostridium difficile infection (CDI) yet the immune deficiency predisposing to CDI is not well understood, despite an increasing incidence of CDI among such individuals. We aimed to estimate the incidence and to evaluate the risk factors of CDI among an HIV cohort in Italy. METHODS: We conducted a retrospective case-control (1:2) study. Clinical records of HIV inpatients admitted to the National Institute for Infectious Disease "L. Spallanzani", Rome, were reviewed (2002-2013). CASES: HIV inpatients with HO-HCFA CDI, and controls: HIV inpatients without CDI, were matched by gender and age. Logistic regression was used to identify risk factors associated with CDI. RESULTS: We found 79 CDI episodes (5.1 per 1000 HIV hospital admissions, 3.4 per 10000 HIV patient-days). The mean age of cases was 46 years. At univariate analysis factors associated with CDI included: antimycobacterial drug exposure, treatment for Pneumocystis pneumonia, acid suppressant exposure, previous hospitalization, antibiotic exposure, low CD4 cell count, high Charlson score, low creatinine, low albumin and low gammaglobulin level. Using multivariate analysis, lower gammaglobulin level and low serum albumin at admission were independently associated with CDI among HIV-infected patients. CONCLUSIONS: Low gammaglobulin and low albumin levels at admission are associated with an increased risk of developing CDI. A deficiency in humoral immunity appears to play a major role in the development of CDI. The potential protective role of albumin warrants further investigation

Olfactory Enrichment Influences Adult Neurogenesis Modulating GAD67 and Plasticity-Related Molecules Expression in Newborn Cells of the Olfactory Bulb

The olfactory bulb (OB) is a highly plastic region of the adult mammalian brain characterized by continuous integration of inhibitory interneurons of the granule (GC) and periglomerular cell (PGC) types. Adult-generated OB interneurons are selected to survive in an experience-dependent way but the mechanisms that mediate the effects of experience on OB neurogenesis are unknown. Here we focus on the new-generated PGC population which is composed by multiple subtypes. Using paradigms of olfactory enrichment and/or deprivation combined to BrdU injections and quantitative confocal immunohistochemical analyses, we studied the effects of olfactory experience on adult-generated PGCs at different survival time and compared PGC to GC modulation. We show that olfactory enrichment similarly influences PGCs and GCs, increasing survival of newborn cells and transiently modulating GAD67 and plasticity-related molecules expression. However, PGC maturation appears to be delayed compared to GCs, reflecting a different temporal dynamic of adult generated olfactory interneuron integration. Moreover, olfactory enrichment or deprivation do not selectively modulate the survival of specific PGC phenotypes, supporting the idea that the integration rate of distinct PGC subtypes is independent from olfactory experience

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Mortality of neuromyelitis optica spectrum disorder patients in an Argentinean population: a study from the RelevarEM registry

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75-2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients

Assessing attacks and treatment response rates among adult patients with NMOSD and MOGAD: data from a nationwide registry in Argentina

We aimed to examine treatment interventions implemented in patients experiencing neuromyelitis optica spectrum disorders (NMOSD) attacks (frequency, types, and response). METHODS: Retrospective study. Data on patient demographic, clinical and radiological findings, and administered treatments were collected. Remission status (complete [CR], partial [PR], no remission [NR]), based on changes in the EDSS score was evaluated before treatment, during attack, and at 6 months. CR was analyzed with a generalized estimating equations (GEEs) model. RESULTS: A total of 131 patients (120 NMOSD and 11 myelin oligodendrocyte glycoprotein-antibody-associated diseases [MOGAD]), experiencing 262 NMOSD-related attacks and receiving 270 treatments were included. High-dose steroids (81.4%) was the most frequent treatment followed by plasmapheresis (15.5%). CR from attacks was observed in 47% (105/223) of all treated patients. During the first attack, we observed CR:71.2%, PR:16.3% and NR:12.5% after the first course of treatment. For second, third, fourth, and fifth attacks, CR was observed in 31.1%, 10.7%, 27.3%, and 33.3%, respectively. Remission rates were higher for optic neuritis vs. myelitis (p < 0.001). Predictor of CR in multivariate GEE analysis was age in both NMOSD (OR = 2.27, p = 0.002) and MOGAD (OR = 1.53, p = 0.03). CONCLUSIONS: This study suggests individualization of treatment according to age and attack manifestation. The outcome of attacks was generally poor