An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways

Zika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks

EnMap In-flight Calibration Status

The Environmental Mapping and Analysis Program (EnMAP) hyperspectral satellite mission was successfully launched on 1st April 2022. The mission aims to monitor and characterise Earth’s environment in the spectral range from 420 - 2450 nm. The VNIR sensor provides 91 science channels ranging from 420 - 1000 nm with an average Spectral Sampling Distance (SSD) of 6.5 nm. While the SWIR sensor covers the range from 900 - 2450 nm with 131 channels and 10nm SSD. - The off-nadir pointing capability (up to 30 degrees) enables 5000 km to be monitored per day, with a swath width of 30 km and a spatial resolution of 30 m. The EnMAP satellite is equipped with several subsystems which allow periodic in-flight monitoring and calibration. The Full Aperture solar Diffuser Assembly (FADA) is used for absolute radiometric calibration. The On-Board Calibration Assembly (OBCA) is composed of 2 integrating spheres: one is coated with a doped diffuser material and is used for the spectral calibration; the second sphere, coated with a white spectralon, is used for Radiometric stability monitoring. Linearity LEDs are placed in front of the detector to monitor their linearity by measuring the response at constant illumination with increasing integration times. The Shutter Calibration Mechanism (SCM) allows for measurements with no light input to be performed in order to compute Dark Signal values and, in combination with Deep Space measurements, to compute any existing shutter emission in the SWIR range. This contribution will present a summary of the calibration activities performed during the EnMAP Commissioning Phase

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Functional analysis of the bZIP transcription factor TGA2.1 in Nicotiana tabacum: Identification of interacting partners and characterization of plants with reduced amounts of TGA2.1

Cis-regulatorische, as-1-ähnliche Elemente vermitteln auxin- und salicylsäureinduzierbare Genexpression in Pflanzen. Sie sind als funktionelle Elemente in einer Reihe von Promotoren enthalten, die im Verlauf pflanzlicher Abwehrreaktionen bei einem Pathogenbefall aktiviert werden. Als Komponenten des pflanzlichen Proteinkomplexes ASF-1 aus Nicotiana tabacum, der an das as-1 Element binden kann, konnten die Klasse II TGA-Faktoren TGA2.2 und TGA2.1 identifiziert werden.Zur Identifizierung potentieller Interaktionspartner von TGA2.1 wurde im Rahmen dieser Arbeit eine cDNA-Bank aus Tabakblättern hergestellt und unter Verwendung des Ubiquitin-based split-protein sensor systems durchgemustert. Es konnte eine DEAD-box RNA-Helicase und eine E2-Ligase als Interaktionspartner identifiziert werden. Zusätzlich konnte im Hefe-Zweihybridsystem eine Wechselwirkung der E2-Ligase mit TGA2.1 nachgewiesen werden, die die Reportergenaktivität des Hefestammes reduzieren kann. Diese Wechselwirkung scheint spezifisch für aktivierende TGA-Faktoren zu sein, da die Koexpression der E2-Ligase zusammen mit TGA1a und TGA10 ebenfalls eine Reduzierung der Reportergenaktivität zur Folge hat. Das gezielte Ausschalten der tga2.1-Expression über RNA-Interferenz in planta zeigte, dass TGA2.1 für die auxin- und salicylsäureabhängige Regulation des frühen Gens Nt103 nicht essentiell ist. Möglicherweise sind die Klasse II TGA-Faktoren TGA2.1 und TGA2.2 in Bezug auf die Regulation des Nt103-Promotors redundant. Für die tga2.1RNAi-Linien im SNN-Hintergrund konnte eine konstitutive PR1a-Expression nachgewiesen werden, die jedoch nicht zu einer erhöhten Resistenz gegenüber einer TMV-Infektion führte. Eine repressorische Funktion von TGA2.1 in Bezug auf die Regulation des späten Gens PR1a sowie die funktionelle Redundanz von TGA2.1 und TGA2.2 wird diskutiert. Zusätzlich zeigten die tga2.1RNAi-Linien im SNN-Hintergrund morphologische Veränderungen. Die transgenen Pflanzen zeichnen sich durch einen geringeren Wuchs, eine vermehrte Bildung von Seitensprossen, eine veränderte Blattform und teilweise durch Sterilität aus

Analysis-Ready Data from Hyperspectral Sensors - The Design of the EnMAP CARD4L-SR Data Product

Today, the ground segments of the Landsat and Sentinel missions provide a wealth of well-calibrated, characterized datasets which are already orthorectified and corrected for atmospheric effects. Initiatives such as the CEOS Analysis Ready Data (ARD) propose and ensure guidelines and requirements so that such datasets can readily be used, and interoperability within and between missions is a given. With the increasing availability of data from operational and research-oriented spaceborne hyperspectral sensors such as EnMAP, DESIS and PRISMA, and in preparation for the upcoming global mapping missions CHIME and SBG, the provision of analysis ready hyperspectral data will also be of increasing interest. Within this article, the design of the EnMAP Level 2A Land product is illustrated, highlighting the necessary processing steps for CEOS Analysis Ready Data for Land (CARD4L) compliant data products. This includes an overview of the design of the metadata, quality layers and archiving workflows, the necessary processing chain (system correction, orthorectification and atmospheric correction), as well as the resulting challenges of this procedure. Thanks to this operational approach, the end user will be provided with ARD products including rich metadata and quality information, which can readily be integrated in analysis workflows, and combined with data from other sensors

In-flight cardiac arrest and in-flight cardiopulmonary resuscitation during commercial air travel : consensus statement and supplementary treatment guideline from the German Society of Aerospace Medicine (DGLRM)

By the end of the year 2016, approximately 3billion people worldwide travelled by commercial air transport. Between 1 out of 14,000 and 1 out of 50,000 passengers will experience acute medical problems/emergencies during a flight (i.e., in-flight medical emergency). Cardiac arrest accounts for 0.3% of all in-flight medical emergencies. So far, no specific guideline exists for the management and treatment of in-flight cardiac arrest (IFCA). A task force with clinical and investigational expertise in aviation, aviation medicine, and emergency medicine was created to develop a consensus based on scientific evidence and compiled a guideline for the management and treatment of in-flight cardiac arrests. Using the GRADE, RAND, and DELPHI methods, a systematic literature search was performed in PubMed. Specific recommendations have been developed for the treatment of IFCA. A total of 29 specific recommendations for the treatment and management of in-flight cardiac arrests were generated. The main recommendations included emergency equipments as well as communication of the emergency. Training of the crew is of utmost importance, and should ideally have a focus on CPR in aircraft. The decision for a diversion should be considered very carefully