The DCR protein TTC3 affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways.

In neuronal cells, actin remodeling plays a well known role in neurite extension but is also deeply involved in the organization of intracellular structures, such as the Golgi apparatus. However, it is still not very clear which mechanisms may regulate actin dynamics at the different sites. In this report we show that high levels of the TTC3 protein, encoded by one of the genes of the Down Syndrome Critical Region (DCR), prevent neurite extension and disrupt Golgi compactness in differentiating primary neurons. These effects largely depend on the capability of TTC3 to promote actin polymerization through signaling pathways involving RhoA, ROCK, CIT-N and PIIa. However, the functional relationships between these molecules differ significantly if considering the TTC3 activity on neurite extension or on Golgi organization. Finally, our results reveal an unexpected stage-dependent requirement for F-actin in Golgi organization at different stages of neuronal differentiation

Secondary stress, intensity and fundamental frequency in Brazilian Portuguese

This paper investigates whether values of acoustical correlates of pretonic syllables adjacent to the one(s) perceived as bearing secondary stress could predict such perception in Brazilian Portuguese (BP) data. In order to pursue this goal, a comparison is made between pretonic syllables perceived as bearing secondary stress and those perceived as not bearing it. According to the results, obtained by application of statistical analyses, it is possible to claim that variation in intensity and in F0 in syllables perceived as bearing secondary stress, as well as in adjacent syllables, can be taken as a robust correlate for data perception regarding secondary stress placement in BP. Variation in intensity and in F0 in syllables perceived as bearing secondary stress and variation in intensity and in F0 in the other adjacent pretonic syllables seem to be complementary information for the perception of secondary stresses by BP speakers. The results point to relevant questions for further work concerning the rhythmic and intonational organization of Brazilian Portuguese.info:eu-repo/semantics/publishedVersio

Mapping and assessment of ecosystems and their services. Urban ecosystems

Action 5 of the EU Biodiversity Strategy to 2020 requires member states to Map and Assess the state of Ecosystems and their Services (MAES). This report provides guidance for mapping and assessment of urban ecosystems. The MAES urban pilot is a collaboration between the European Commission, the European Environment Agency, volunteering Member States and cities, and stakeholders. Its ultimate goal is to deliver a knowledge base for policy and management of urban ecosystems by analysing urban green infrastructure, condition of urban ecosystems and ecosystem services. This report presents guidance for mapping urban ecosystems and includes an indicator framework to assess the condition of urban ecosystems and urban ecosystem services. The scientific framework of mapping and assessment is designed to support in particular urban planning policy and policy on green infrastructure at urban, metropolitan and regional scales. The results are based on the following different sources of information: a literature survey of 54 scientific articles, an online-survey (on urban ecosystems, related policies and planning instruments and with participation of 42 cities), ten case studies (Portugal: Cascais, Oeiras, Lisbon; Italy: Padua, Trento, Rome; The Netherlands: Utrecht; Poland: Poznań; Spain: Barcelona; Norway: Oslo), and a two-day expert workshop. The case studies constituted the core of the MAES urban pilot. They provided real examples and applications of how mapping and assessment can be organized to support policy; on top, they provided the necessary expertise to select a set of final indicators for condition and ecosystem services. Urban ecosystems or cities are defined here as socio-ecological systems which are composed of green infrastructure and built infrastructure. Urban green infrastructure (GI) is understood in this report as the multi-functional network of urban green spaces situated within the boundary of the urban ecosystem. Urban green spaces are the structural components of urban GI. This study has shown that there is a large scope for urban ecosystem assessments. Firstly, urban policies increasingly use urban green infrastructure and nature-based solutions in their planning process. Secondly, an increasing amount of data at multiple spatial scales is becoming available to support these policies, to provide a baseline, and to compare or benchmark cities with respect to the extent and management of the urban ecosystem. Concrete examples are given on how to delineate urban ecosystems, how to choose an appropriate spatial scale, and how to map urban ecosystems based on a combination of national or European datasets (including Urban Atlas) and locally collected information (e.g., location of trees). Also examples of typologies for urban green spaces are presented. This report presents an indicator framework which is composed of indicators to assess for urban ecosystem condition and for urban ecosystem services. These are the result of a rigorous selection process and ensure consistent mapping and assessment across Europe. The MAES urban pilot will continue with work on the interface between research and policy. The framework presented in this report needs to be tested and validated across Europe, e.g. on its applicability at city scale, on how far the methodology for measuring ecosystem condition and ecosystem service delivery in urban areas can be used to assess urban green infrastructure and nature-based solutions

Imaging biomarkers of lung ventilation in interstitial lung disease from ¹²⁹Xe and oxygen enhanced ¹H MRI

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI performed at 1.5 T. Inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF

Serum neurofilament-light concentration and real-world outcome in MS

Background Prognostication in multiple sclerosis (MS) remains challenging. Biomarkers capable of providing this information at diagnosis would be valuable in shaping therapeutic decisions. Measurement of neurofilament light (NfL) has shown promise in predicting clinical outcomes in established MS, but its ability to predict outcomes in real-world cohorts at diagnosis requires further validation. Methods We used linear regression to evaluate the relationship between serum NfL (sNfL), measured at the time of diagnosis with short-term (1-year) and medium-term (5-year) clinical outcomes in 164 people with MS from a real-world, population-based cohort. Cox proportional hazards regression was used to analyse the association between sNfL and subsequent hazard of relapse or sustained accumulation of disability (SAD). Analyses were adjusted for age and disease-modifying treatment (DMT). Results sNfL concentration at diagnosis was modestly associated with baseline EDSS score (β = 0.272, 95% CI 0.051 to 0.494, p = 0.016). However, no significant associations were found between baseline sNfL and odds of relapse at 12-months, 5-year EDSS change, or the hazard of relapse or SAD over 5 years follow-up. Dichotomising baseline sNfL according to the median sNfL did not change these findings. Conclusions sNfL appears to be of limited clinical utility in predicting future irreversible neurological disability in a largely untreated real-world population, and remains insufficiently validated to shape treatment decisions at the time of diagnosis. Further studies may be needed for sNfL to be considered as a prognostic marker in the MS clinic. However the masking effect of DMTs on the natural disease trajectory will continue to pose challenges

A Viable Hypomorphic Allele of the Essential IMP3 Gene Reveals Novel Protein Functions in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the essential IMP3 gene encodes a component of the SSU processome, a large ribonucleoprotein complex required for processing of small ribosomal subunit RNA precursors. Mutation of the IMP3 termination codon to a sense codon resulted in a viable mutant allele producing a C-terminal elongated form of the Imp3 protein. A strain expressing the mutant allele displayed ribosome biogenesis defects equivalent to IMP3 depletion. This hypomorphic allele represented a unique opportunity to investigate and better understand the Imp3p functions. We demonstrated that the +1 frameshifting was increased in the mutant strain. Further characterizations revealed involvement of the Imp3 protein in DNA repair and telomere length control, pointing to a functional relationship between both pathways and ribosome biogenesis

Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR

Simulation results for future measurements of electromagnetic proton form factors at \PANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel $\bar p p \to e^+ e^-$ is studied on the basis of two different but consistent procedures. The suppression of the main background channel, $\textit{i.e.}$ $\bar p p \to \pi^+ \pi^-$, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance

XIPE: the X-ray Imaging Polarimetry Explorer

X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068