The little-studied cluster Berkeley 90 I. LS III +46 11: a very massive O3.5 If* + O3.5 If* binary

Context. It appears that most (if not all) massive stars are born in multiple systems. At the same time, the most massive binaries are hard to find owing to their low numbers throughout the Galaxy and the implied large distances and extinctions. Aims. We want to study LS III +46 11, identified in this paper as a very massive binary; another nearby massive system, LS III +46 12; and the surrounding stellar cluster, Berkeley 90. Methods. Most of the data used in this paper are multi-epoch high S/N optical spectra, although we also use Lucky Imaging and archival photometry. The spectra are reduced with dedicated pipelines and processed with our own software, such as a spectroscopic-orbit code, CHORIZOS, and MGB. Results. LS III +46 11 is identified as a new very early O-type spectroscopic binary [O3.5 If* + O3.5 If*] and LS III +46 12 as another early O-type system [O4.5 V((f))]. We measure a 97.2-day period for LS III +46 11 and derive minimum masses of 38.80 ± 0.83 M⊙ and 35.60 ± 0.77 M⊙ for its two stars. We measure the extinction to both stars, estimate the distance, search for optical companions, and study the surrounding cluster. In doing so, a variable extinction is found as well as discrepant results for the distance. We discuss possible explanations and suggest that LS III +46 12 may be a hidden binary system where the companion is currently undetected.J.M.A. and A.S. acknowledge support from [a] the Spanish Government Ministerio de Economía y Competitividad (MINECO) through grants AYA2010-15 081, AYA2010-17 631, and AYA2013-40 611-P and [b] the Consejería de Educación of the Junta de Andalucía through grant P08-TIC-4075. J.M.A. was also supported by the George P. and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy and he is grateful to the Department of Physics and Astronomy at Texas A&M University for their hospitality during some of the time this work was carried out. I.N., A.M., J.A., and J.L. acknowledge support from [a] the Spanish Government Ministerio de Economía y Competitividad (MINECO) through grant AYA2012-39 364-C02-01/02, [b] the European Union, and [c] the Generalitat Valenciana through grant ACOMP/2014/129. R.H.B. acknowledges support from FONDECYT Project 1 140 076. S.S.-D. acknowledges funding by [a] the Spanish Government Ministerio de Economía y Competitividad (MINECO) through grants AYA2010-21 697-C05-04, AYA2012-39 364-C02-01, and Severo Ochoa SEV-2011-0187 and [b] the Canary Islands Government under grant PID2 010 119. J.S.-B. acknowledges support by the JAE-PreDoc program of the Spanish Consejo Superior de Investigaciones Científicas (CSIC). STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555

Radial evolution of the April 2020 stealth coronal mass ejection between 0.8 and 1 AU - Comparison of Forbush decreases at Solar Orbiter and near the Earth

Aims. We present observations of the first coronal mass ejection (CME) observed at the Solar Orbiter spacecraft on April 19, 2020, and the associated Forbush decrease (FD) measured by its High Energy Telescope (HET). This CME is a multispacecraft event also seen near Earth the next day. Methods. We highlight the capabilities of HET for observing small short-term variations of the galactic cosmic ray count rate using its single detector counters. The analytical ForbMod model is applied to the FD measurements to reproduce the Forbush decrease at both locations. Input parameters for the model are derived from both in situ and remote-sensing observations of the CME. Results. The very slow (~350 km/s) stealth CME caused a FD with an amplitude of 3 % in the low-energy cosmic ray measurements at HET and 2 % in a comparable channel of the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter, as well as a 1 % decrease in neutron monitor measurements. Significant differences are observed in the expansion behavior of the CME at different locations, which may be related to influence of the following high speed solar wind stream. Under certain assumptions, ForbMod is able to reproduce the observed FDs in low-energy cosmic ray measurements from HET as well as CRaTER, but with the same input parameters, the results do not agree with the FD amplitudes at higher energies measured by neutron monitors on Earth. We study these discrepancies and provide possible explanations. Conclusions. This study highlights that the novel measurements of the Solar Orbiter can be coordinated with other spacecraft to improve our understanding of space weather in the inner heliosphere. Multi-spacecraft observations combined with data-based modeling are also essential to understand the propagation and evolution of CMEs as well as their space weather impacts

First year of energetic particle measurements in the inner heliosphere with Solar Orbiter's Energetic Particle Detector

Context. Solar Orbiter strives to unveil how the Sun controls and shapes the heliosphere and fills it with energetic particle radiation. To this end, its Energetic Particle Detector (EPD) has now been in operation, providing excellent data, for just over a year. Aims. EPD measures suprathermal and energetic particles in the energy range from a few keV up to (near-) relativistic energies (few MeV for electrons and about 500 MeV nuc−1 for ions). We present an overview of the initial results from the first year of operations and we provide a first assessment of issues and limitations. In addition, we present areas where EPD excels and provides opportunities for significant scientific progress in understanding how our Sun shapes the heliosphere. Methods. We used the solar particle events observed by Solar Orbiter on 21 July and between 10 and 11 December 2020 to discuss the capabilities, along with updates and open issues related to EPD on Solar Orbiter. We also give some words of caution and caveats related to the use of EPD-derived data. Results. During this first year of operations of the Solar Orbiter mission, EPD has recorded several particle events at distances between 0.5 and 1 au from the Sun. We present dynamic and time-averaged energy spectra for ions that were measured with a combination of all four EPD sensors, namely: the SupraThermal Electron and Proton sensor (STEP), the Electron Proton Telescope (EPT), the Suprathermal Ion Spectrograph (SIS), and the High-Energy Telescope (HET) as well as the associated energy spectra for electrons measured with STEP and EPT. We illustrate the capabilities of the EPD suite using the 10 and 11 December 2020 solar particle event. This event showed an enrichment of heavy ions as well as 3He, for which we also present dynamic spectra measured with SIS. The high anisotropy of electrons at the onset of the event and its temporal evolution is also shown using data from these sensors. We discuss the ongoing in-flight calibration and a few open instrumental issues using data from the 21 July and the 10 and 11 December 2020 events and give guidelines and examples for the usage of the EPD data. We explain how spacecraft operations may affect EPD data and we present a list of such time periods in the appendix. A list of the most significant particle enhancements as observed by EPT during this first year is also provided.Ministerio de Economía y CompetitividadAgencia Estatal de Investigació

Detection and Functional Characterization of a 215 Amino Acid N-Terminal Extension in the Xanthomonas Type III Effector XopD

During evolution, pathogens have developed a variety of strategies to suppress plant-triggered immunity and promote successful infection. In Gram-negative phytopathogenic bacteria, the so-called type III protein secretion system works as a molecular syringe to inject type III effectors (T3Es) into plant cells. The XopD T3E from the strain 85-10 of Xanthomonas campestris pathovar vesicatoria (Xcv) delays the onset of symptom development and alters basal defence responses to promote pathogen growth in infected tomato leaves. XopD was previously described as a modular protein that contains (i) an N-terminal DNA-binding domain (DBD), (ii) two tandemly repeated EAR (ERF-associated amphiphillic repression) motifs involved in transcriptional repression, and (iii) a C-terminal cysteine protease domain, involved in release of SUMO (small ubiquitin-like modifier) from SUMO-modified proteins. Here, we show that the XopD protein that is produced and secreted by Xcv presents an additional N-terminal extension of 215 amino acids. Closer analysis of this newly identified N-terminal domain shows a low complexity region rich in lysine, alanine and glutamic acid residues (KAE-rich) with high propensity to form coiled-coil structures that confers to XopD the ability to form dimers when expressed in E. coli. The full length XopD protein identified in this study (XopD1-760) displays stronger repression of the XopD plant target promoter PR1, as compared to the XopD version annotated in the public databases (XopD216-760). Furthermore, the N-terminal extension of XopD, which is absent in XopD216-760, is essential for XopD type III-dependent secretion and, therefore, for complementation of an Xcv mutant strain deleted from XopD in its ability to delay symptom development in tomato susceptible cultivars. The identification of the complete sequence of XopD opens new perspectives for future studies on the XopD protein and its virulence-associated functions in planta

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)