The immunological and virological events that contribute to the establishment of Zika virus (ZIKV) infection in humans are unclear. Here, we show that robust cellular innate immune responses arising early in the blood and tissues in response to ZIKV infection are significantly stronger in males and correlate with increased viral persistence. In particular, early peripheral blood recruitment of plasmacytoid dendritic…
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Chromosome segregation depends on the kinetochore, the machine that establishes force-bearing attachments between DNA and spindle microtubules. Kinetochores are formed every cell cycle via a highly regulated process that requires coordinated assembly of multiple subcomplexes on specialized chromatin. To elucidate the underlying mechanisms, we developed an assay to assemble kinetochores de novo using centromeric DNA and budding yeast extracts. Assembly…
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Two phase 3 placebo-controlled trials of the CYD-TDV vaccine, evaluated in children aged 2-14 y (CYD14) and 9-16 y (CYD15), demonstrated vaccine efficacy (VE) of 56.5% and 60.8%, respectively, against symptomatic virologically confirmed dengue (VCD). Sieve analyses were conducted to evaluate whether and how VE varied with amino acid sequence features of dengue viruses (DENVs). DENV premembrane/envelope amino acid sequences…
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Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We…
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The SET1/MLL family of histone methyltransferases is conserved in eukaryotes and regulates transcription by catalyzing histone H3K4 mono-, di-, and tri-methylation. These enzymes form a common five-subunit catalytic core whose assembly is critical for their basal and regulated enzymatic activities through unknown mechanisms. Here, we present the crystal structure of the intact yeast COMPASS histone methyltransferase catalytic module consisting of Swd1, Swd3,…
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The influenza virus hemagglutinin (HA) fusion glycoprotein mediates viral entry into host cells through its receptor binding and membrane fusion activities. In this issue of Cell, Das et al. use single-molecule Förster resonance energy transfer (smFRET) to monitor HA conformational dynamics. Their study reveals this prototypical class I fusion protein to be a highly dynamic molecule capable of reversibly sampling multiple…
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CD8+ T cells respond to signals via the T cell receptor (TCR), costimulatory molecules, and immunoregulatory cytokines by developing into diverse populations of effector and memory cells. The relative strength of phosphoinositide 3-kinase (PI3K) signaling early in the T cell response can dramatically influence downstream effector and memory T cell differentiation. We show that initial PI3K signaling during T cell activation…
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The complexity of microbial communities, combined with technical biases in next-generation sequencing, pose a challenge to metagenomic analysis. Here, we develop a set of internal DNA standards, termed “sequins” (sequencing spike-ins), that together constitute a synthetic community of artificial microbial genomes. Sequins are added to environmental DNA samples prior to library preparation, and undergo concurrent sequencing with the accompanying sample.…
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New Tools for Syphilis Research

Syphilis research has been severely limited by the necessity to propagate Treponema pallidumin vivo in rabbits. After decades of erroneous or irreproducible reports of cultivation of T. pallidum, the recent very convincing report of its successful long-term in vitro propagation opens numerous opportunities for development of genetictools for studying pathogenesis and protein function, antigenic variation, and surface exposure of antigens. The possibility of more rapid isolation of…
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Iodide Improves Outcome After Acute Myocardial Infarction in Rats and Pigs

In this study, we tested whether iodide would reduce heart damage in rat and pig models of acute myocardial infarction as a risk analysis for a human trial. Acute myocardial infarction was induced by temporary ligation of the coronary artery followed by reperfusion. Iodide was administered orally in rats or IV in rats and pigs just prior to reperfusion. Damage was assessed by blood…
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