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We report the first demonstration of Raman amplification in a fiber of a single Bessel-like higher order mode using a multimode pump source. We amplify the LP08-mode with a 559-mu m(2) effective mode area at a signal wavelength of 1115 nm in a pure-silica-core step-index fiber. A maximum of 18 dB average power gain is achieved in a 9-m long gain fiber, with output pulse energy of 115 mu J. The Raman pump source comprises a pulsed 1060 nm ytterbium-doped fiber amplifier with V-value similar to 30, which is matched to the Raman gain fiber. The pump depletion as averaged over the signal pulses reaches 36.7%. The conversion of power from the multimode pump into the signal mode demonstrates the potential for efficient brightness enhancement with low amplification-induced signal mode purity degradation. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.

OPRM1 A118G, a functional human mu-opioid receptor (MOR) polymorphism, is associated with drug dependence and altered stress responsivity in humans as well as altered MOR signaling. MOR signaling can regulate many cellular processes, including gene expression, and many of the long-term, stable effects of drugs and stress may stem from changes in gene expression in diverse brain regions. A mouse model bearing an equivalent polymorphism (Oprm1 A112G) was previously generated and studied. Mice homozygous for the G112 allele show differences in opioid- and stress-related phenotypes. The current study examines the expression of 24 genes related to drug and stress responsivity in the caudoputamen, nucleus accumbens, hypothalamus, hippocampus, and amygdala of drug-na < ve, stress-minimized, male and female mice homozygous for either the G112 variant allele or the wild-type A112 allele. We detected nominal genotype-dependent changes in gene expression of multiple genes. We also detected nominal sex-dependent as well as sex-by-genotype interaction effects on gene expression. Of these, four genotype-dependent differences survived correction for multiple testing: Avp and Gal in the hypothalamus and Oprl1 and Cnr1 in the hippocampus. Changes in the regulation of these genes by mu-opioid receptors encoded by the G112 allele may be involved in some of the behavioral and molecular consequences of this polymorphism observed in mice.

search is presented for physics beyond the standard model, based on measurements of dijet angular distributions in proton-proton collisions at root s = 13 TeV. The data collected with the CMS detector at the LHC correspond to an integrated luminosity of 35.9 fb(-1). The observed distributions, corrected to particle level, are found to be in agreement with predictions from perturbative quantum chromodynamics that include electroweak corrections. Constraints are placed on models containing quark contact interactions, extra spatial dimensions, quantum black holes, or dark matter, using the detector-level distributions. In a benchmark model where only left-handed quarks participate, contact interactions are excluded at the 95% confidence level up to a scale of 12.8 or 17.5 TeV, for destructive or constructive interference, respectively. The most stringent lower limits to date are set on the ultraviolet cutoff in the Arkani-Hamed-Dimopoulos-Dvali model of extra dimensions. In the Giudice-Rattazzi-Wells convention, the cutoff scale is excluded up to 10.1 TeV. The production of quantum black holes is excluded for masses below 5.9 and 8.2 TeV, depending on the model. For the first time, lower limits between 2.0 and 4.6 TeV are set on the mass of a dark matter mediator for (axial-)vector mediators, for the universal quark coupling g(q) = 1.0.

RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here, we performed a large-scale screen using Caenorhabditis elegans and its natural pathogen the Orsay virus (OrV), and we identified cde-1 as important for antiviral defense. CDE-1 is a homolog of the mammalian TUT4 and TUT7 terminal uridylyltransferases (collectively called TUT4(7)); its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3' end of the OrV RNA genome and promotes its degradation in a manner independent of the RNAi pathway. Likewise, TUT4(7) enzymes uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4(7) leads to increased IAV mRNA and protein levels. Collectively, these data implicate 3'-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.

Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a central regulator of innate immune signaling, controlling IL1R and Toll-like receptor (TLR)-mediated responses and containing both scaffolding and kinase activities. Humans deficient in IRAK4 activity have autosomal recessive primary immune deficiency (PID). Here, we characterized the molecular mechanism of dysfunction of two IRAK4 PID variants, G298D and the compound variant R12C (R12C/R391H/T458I). Using these variants and the kinase-inactive D329A variant to delineate the contributions of IRAK4's scaffolding and kinase activities to IL1R signaling, we found that the G298D variant is kinase-inactive and expressed at extremely low levels, acting functionally as a null mutation. The R12C compound variant possessed WT kinase activity, but could not interact with myeloid differentiation primary response 88 (MyD88) and IRAK1, causing impairment of IL-1-induced signaling and cytokine production. Quantitation of IL-1 signaling in IRAK4-deficient cells complemented with either WT or the R12C or D329A variant indicated that the loss of MyD88 interaction had a greater impact on IL-1-induced signaling and cytokine expression than the loss of IRAK4 kinase activity. Importantly, kinase-inactive IRAK4 exhibited a greater association with MyD88 and a weaker association with IRAK1 in IRAK4-deficient cells expressing kinase-inactive IRAK4 and in primary cells treated with a selective IRAK4 inhibitor. Loss of IRAK4 kinase activity only partially inhibited IL-1-induced cytokine and NF-B signaling. Therefore, the IRAK4-MyD88 scaffolding function is essential for IL-1 signaling, but IRAK4 kinase activity can control IL-1 signal strength by modulating the association of IRAK4, MyD88, and IRAK1.

Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure.

It has been known that the dorsal and ventral areas of the dentate gyrus in the hippocampus have distinct roles in memory and mood behaviors. We previously reported that microRNA miR-17-92 regulates adult hippocampal neurogenesis and mood disorders. Here, we suggest that the miR-17-92 cluster is highly expressed in the ventral than the dorsal dentate gyrus in the adult mouse hippocampus. Deletion of mi R-17-92 in the adult hippocampus only affects development of neural progenitors in the ventral dentate gyrus, and miR-17-92 knockout mice have no defects in memory functions. Our results suggest that regional expression of miR-17-92 in the dentate gyrus is associated with their distinct functions in hippocampal neurogenesis and related behaviors. (C) 2018 Elsevier Inc. All rights reserved.