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  • Rasch Burke posted an update 2 weeks, 4 days ago

    We also benchmark the performance of baseline and state-of-the-art deep learning approaches on the dataset, demonstrating how it can be used to evaluate automatically generated summaries.Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.Zika virus (ZIKV) is an emerging mosquito borne flavivirus and a major public health concern causing severe disease. Due to the presence of a lipid membrane and structural heterogeneity, attaining an atomic resolution structure is challenging, but important to understand virus assembly and life cycle mechanisms that offer distinct targets for therapeutic intervention. We here use subvolume refinement to achieve a 3.4 Å resolution structure and identify two distinct lipid moieties. The first arises from the inner leaflet and is coordinated by hydrophobic residues of the M and E transmembrane helices that form a binding pocket not previously characterized. The second lipid arises from the outer leaflet coordinate between two E protein helices. Structure-based mutagenesis identifies critical hydrophobic interactions and their effect on the virus life cycle. Results show that lipids play an essential role in the ZIKV assembly pathway revealing a potential target of lipid based antiviral drug development.The structure and dynamics of liquids on curved surfaces are often studied through the lens of frustration-based approaches to the glass transition. Competing glass transition theories, however, remain largely untested on such surfaces and moreover, studies hitherto have been entirely theoretical/numerical. Here we carry out single particle-resolved imaging of dynamics of bi-disperse colloidal liquids confined to the surface of a sphere. We find that mode-coupling theory well captures the slowing down of dynamics in the moderate to deeply supercooled regime. Strikingly, the morphology of cooperatively rearranging regions changed from string-like to compact near the mode-coupling crossover-a prediction unique to the random first-order theory of glasses. Further, we find that in the limit of strong curvature, Mermin-Wagner long-wavelength fluctuations are irrelevant and liquids on a sphere behave like three-dimensional liquids. A comparative evaluation of competing mechanisms is thus an essential step towards uncovering the true nature of the glass transition.Achieving current electricity sector targets in Central Europe (Austria, Denmark, France, Germany, Poland and Switzerland) will redistribute regional benefits and burdens at sub-national level. Limiting emerging regional inequalities would foster the implementation success. MRTX849 molecular weight We model one hundred scenarios of electricity generation, storage and transmission for 2035 in these countries for 650 regions and quantify associated regional impacts on system costs, employment, greenhouse gas and particulate matter emissions, and land use. We highlight tradeoffs among the scenarios that minimize system costs, maximize regional equality, and maximize renewable electricity generation. Here, we show that these three aims have vastly different implementation pathways as well as associated regional impacts and cannot be optimized simultaneously. Minimizing system costs leads to spatially-concentrated impacts. Maximizing regional equality of system costs has higher, but more evenly distributed impacts. Maximizing renewable electricity generation contributes to minimizing regional inequalities, although comes at higher costs and land use impacts.Numerous ecosystem manipulative experiments have been conducted since 1970/80 s to elucidate responses of terrestrial carbon cycling to the changing atmospheric composition (CO2 enrichment and nitrogen deposition) and climate (warming and changing precipitation regimes), which is crucial for model projection and mitigation of future global change effects. Here, we extract data from 2,242 publications that report global change manipulative experiments and build a comprehensive global database with 5,213 pairs of samples for plant production (productivity, biomass, and litter mass) and ecosystem carbon exchange (gross and net ecosystem productivity as well as ecosystem and soil respiration). Information on climate characteristics and vegetation types of experimental sites as well as experimental facilities and manipulation magnitudes subjected to manipulative experiments are also included in this database. This global database can facilitate the estimation of response and sensitivity of key terrestrial carbon-cycling variables under future global change scenarios, and improve the robust projection of global change‒terrestrial carbon feedbacks imposed by Earth System Models.Genetic variation is of crucial importance for crop improvement. Landraces are valuable sources of diversity, but for quantitative traits efficient strategies for their targeted utilization are lacking. Here, we map haplotype-trait associations at high resolution in ~1000 doubled-haploid lines derived from three maize landraces to make their native diversity for early development traits accessible for elite germplasm improvement. A comparative genomic analysis of the discovered haplotypes in the landrace-derived lines and a panel of 65 breeding lines, both genotyped with 600k SNPs, points to untapped beneficial variation for target traits in the landraces. The superior phenotypic performance of lines carrying favorable landrace haplotypes as compared to breeding lines with alternative haplotypes confirms these findings. Stability of haplotype effects across populations and environments as well as their limited effects on undesired traits indicate that our strategy has high potential for harnessing beneficial haplotype variation for quantitative traits from genetic resources.