The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Abstract
The Allele Frequency Net Database (AFND, www.allelefrequencies.net) provides the scientific community with a freely available repository for the storage of frequency data (alleles, genes, ...haplotypes and genotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex Class I chain related genes (MIC) and a number of cytokine gene polymorphisms in worldwide populations. In the last five years, AFND has become more popular in terms of clinical and scientific usage, with a recent increase in genotyping data as a necessary component of Short Population Report article submissions to another scientific journal. In addition, we have developed a user-friendly desktop application for HLA and KIR genotype/population data submissions. We have also focused on classification of existing and new data into ‘gold–silver–bronze’ criteria, allowing users to filter and query depending on their needs. Moreover, we have also continued to expand other features, for example focussed on HLA associations with adverse drug reactions. At present, AFND contains >1600 populations from >10 million healthy individuals, making AFND a valuable resource for the analysis of some of the most polymorphic regions in the human genome.
Abstract
The phase of the quantum-mechanical wave function can encode a topological structure with wide-ranging physical consequences, such as anomalous transport effects and the existence of edge ...states robust against perturbations. While this has been exhaustively demonstrated for electrons, properties associated with the elementary quasiparticles in magnetic materials are still underexplored. Here, we show theoretically and via inelastic neutron scattering experiments that the bulk ferromagnet Mn
5
Ge
3
hosts gapped topological Dirac magnons. Although inversion symmetry prohibits a net Dzyaloshinskii-Moriya interaction in the unit cell, it is locally allowed and is responsible for the gap opening in the magnon spectrum. This gap is predicted and experimentally verified to close by rotating the magnetization away from the
c
-axis with an applied magnetic field. Hence, Mn
5
Ge
3
realizes a gapped Dirac magnon material in three dimensions. Its tunability by chemical doping or by thin film nanostructuring defines an exciting new platform to explore and design topological magnons. More generally, our experimental route to verify and control the topological character of the magnons is applicable to bulk centrosymmetric hexagonal materials, which calls for systematic investigation.
Many sequence variants have been linked to complex human traits and diseases
, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have ...systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in the human genome using an ultra-high-throughput multiplex protein-DNA binding assay, termed single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment (SNP-SELEX). The resulting 828 million measurements of transcription factor-DNA interactions enable estimation of the relative affinity of these transcription factors to each variant in vitro and evaluation of the current methods to predict the effects of noncoding variants on transcription factor binding. We show that the position weight matrices of most transcription factors lack sufficient predictive power, whereas the support vector machine combined with the gapped k-mer representation show much improved performance, when assessed on results from independent SNP-SELEX experiments involving a new set of 61,020 sequence variants. We report highly predictive models for 94 human transcription factors and demonstrate their utility in genome-wide association studies and understanding of the molecular pathways involved in diverse human traits and diseases.
► We isolated of the S. cerevisiae LBM-1 strain, which is capable of growth at 42°C. ► We compared the capacity of different yeast strains to ferment sugar cane bagasse. ► Presaccharification stage ...is key to increasing ethanol yields. ► Use of thermotolerant yeasts increase the yield of the SSF process.
Ethanol can be produced from cellulosic biomass in a process known as simultaneous saccharification and fermentation (SSF). The presence of yeast together with the cellulolytic enzyme complex reduces the accumulation of sugars within the reactor, increasing the ethanol yield and saccharification rate. This paper reports the isolation of Saccharomyces cerevisiae LBM-1, a strain capable of growth at 42°C. In addition, S. cerevisiae LBM-1 and Kluyveromyces marxianus UFV-3 were able to ferment sugar cane bagasse in SSF processes at 37 and 42°C. Higher ethanol yields were observed when fermentation was initiated after presaccharification at 50°C than at 37 or 42°C. Furthermore, the volumetric productivity of fermentation increased with presaccharification time, from 0.43g/L/h at 0h to 1.79g/L/h after 72h of presaccharification. The results suggest that the use of thermotolerant yeasts and a presaccharification stage are key to increasing yields in this process.
Since December 2016, Brazil has experienced an unusually large outbreak of yellow fever (YF). Whether urban transmission may contribute to the extent of the outbreak is unclear. The objective of this ...study was to characterize YF virus (YFV) genomes and to identify spatial patterns to determine the distribution and origin of YF cases in Minas Gerais, Espírito Santo and Rio de Janeiro, the most affected Brazilian states during the current YFV outbreak.
We characterized near-complete YFV genomes from 14 human cases and two nonhuman primates (NHP), sampled from February to April 2017, retrieved epidemiologic data of cases and used a geographic information system to investigate the geospatial spread of YFV.
All YFV strains were closely related. On the basis of signature mutations, we identified two cocirculating YFV clusters. One was restricted to the hinterland of Espírito Santo state, and another formed a coastal cluster encompassing several hundred kilometers. Both clusters comprised strains from humans living in rural areas and NHP. Another NHP lineage clustered in a basal relationship. No signs of adaptation of YFV strains to human hosts were detected.
Our data suggest sylvatic transmission during the current outbreak. Additionally, cocirculation of two distinct YFV clades occurring in humans and NHP suggests the existence of multiple sylvatic transmission cycles. Increased detection of YFV might be facilitated by raised awareness for arbovirus-mediated disease after Zika and chikungunya virus outbreaks. Further surveillance is required, as reemergence of YFV from NHPs might continue and facilitate the appearance of urban transmission cycles.
Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of ...β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.
Collectively, reservoirs created by dams are thought to be an important source of greenhouse gases (GHGs) to the atmosphere. So far, efforts to quantify, model, and manage these emissions have been ...limited by data availability and inconsistencies in methodological approach. Here, we synthesize reservoir CH4, CO2, and N2O emission data with three main objectives: (1) to generate a global estimate of GHG emissions from reservoirs, (2) to identify the best predictors of these emissions, and (3) to consider the effect of methodology on emission estimates. We estimate that GHG emissions from reservoir water surfaces account for 0.8 (0.5–1.2) Pg CO2 equivalents per year, with the majority of this forcing due to CH4. We then discuss the potential for several alternative pathways such as dam degassing and downstream emissions to contribute significantly to overall emissions. Although prior studies have linked reservoir GHG emissions to reservoir age and latitude, we find that factors related to reservoir productivity are better predictors of emission.
PDF
