The Hantaan Virus Glycoprotein Precursor Is Cleaved at the Conserved Pentapeptide WAASA

AbstractThe medium segment of the tripartite negative-stranded RNA genome of hantaviruses encodes for the predicted glycoprotein precursor GPC. We have demonstrated here the expression of the glycoprotein precursor of Hantaan virus following transfection of mammalian cells. The cleavage of the precursor into the glycoproteins G1 and G2 followed the rules for signal peptides and seemed to occur directly at the pentapeptide motif “WAASA.” Our data indicate that the signal peptidase complex is responsible for the proteolytic processing of the precursor GPC of Hantaan virus. The comparison of this region of the glycoprotein precursor, including the absolutely conserved WAASA motif, suggests a similar cleavage event for all hantavirus glycoproteins

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated

User-oriented development of global emission inventories: Bottom-up modeling of emissions from land transport, aviation and shipping in the DLR project ELK

The transport sector accounts for about one quarter of worldwide anthropogenic carbon dioxide emissions. Since a robust growth in transport activity is expected over the coming decades, reducing associated emissions to mitigate human-caused climate change is a particular challenge. In order to achieve high-quality comparative monitoring, to develop scenarios for future emissions, and to enable a robust assessment of climate protection measures, the allocation of emissions to the subsector level is a necessary prerequisite. The DLR project ELK - EmissionsLandKarte (en.: emission map) contributes here in several respects: (1) requirements are specified in an application-based manner, i.e. compatibility with existing inventories, such as the ones generated for IPCC, is ensured and insufficiencies in spatial resolution and methodological detail are addressed, (2) an input database congruent with both statistical data and SSP scenarios is provided, and (3) bottom-up calculations are performed that allow attribution of climate impacts to specific transport services, as well as prospective analyses where, for example, activity levels change or alternative fuels affect regional emission factors. The resulting prototype global gas and particle emission inventories for land transport, aviation and shipping reflect the status quo as of 2019. For land transport, fine-grained activity and vehicle fleet data as well as technology-specific emission factors are applied. This allows emissions from passenger and freight transport to be disaggregated by mode and vehicle type. New approaches for spatial disaggregation of emissions will increase transparency of the methodology. For aviation, calculations are based on fleet composition and transport performance for both passenger and cargo traffic at the airport pair level, while real flight tracks serve as the foundation for spatial allocation. For both transport sectors, complementary analyses are performed to characterize particulate emissions in order to fill gaps in data availability. For shipping, transport performance on inland waterways and maritime routes are considered, including technical data describing propulsion and bunkering. Finally, all mode-specific results are subjected to an innovative uncertainty assessment aligned with the needs of other emission inventory creators through a detailed evaluation per uncertainty factor, as well as aggregated values for climate modelers and practitioners. The consistent assessment of uncertainty factors along the entire calculation chain, such as activity levels, emission factors, and proxy data used for spatial or temporal disaggregation, promotes comparability across all transport sectors. In this paper, we outline the new methodological approaches for mapping transport emissions and present first results