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The top-quark pair production cross section in 7 TeV center-of-mass energy proton-proton collisions is measured using data collected by the CMS detector at the LHC. The measurement uses events with one jet identified as a hadronically decaying tau lepton and at least four additional energetic jets, at least one of which is identified as coming from a b quark. The analyzed data sample corresponds to an integrated luminosity of 3.9 fb(-1) recorded by a dedicated multijet plus hadronically decaying tau trigger. A neural network has been developed to separate the top-quark pairs from the W + jets and multijet backgrounds. The measured value of sigma(t (t) over bar) = 152 +/- 12 (stat.) +/- 32 (syst.) +/- 3 (lum.) pb is consistent with the standard model predictions.

The W+W- and ZZ production cross sections are measured in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC in data samples corresponding to an integrated luminosity of up to 5.3 fb(-1). The measurements are performed in the leptonic decay modes W+W- -> l'vl '' v and ZZ -> 2l2l', where l = e, mu and l'(l '') = e, mu, tau. The measured cross sections sigma (pp -> W+W-) =, 69.9 +/- 2.8 (stat.) +/- 5.6 (syst.) 3.1 +/- (lum.) pb and sigma (pp -> ZZ) = 8.4 +/- 1.0 (stat) +/- 0.7 (syst) +/- 0.4 (lum.) pb, for both Z bosons produced in the mass region 60 < m(Z) < 120 GeV, are consistent with standard model predictions. These are the first measurements of the diboson production cross sections at root s = 8 TeV. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.

Tetherin (Bst2/CD317/HM1.24) is an interferon-induced antiviral host protein that inhibits the release of many enveloped viruses by tethering virions to the cell surface. The HIV-1 accessory protein, Vpu, antagonizes Tetherin through a variety of proposed mechanisms, including surface downregulation and degradation. Previous studies have demonstrated that mutation of the transmembrane domains (TMD) of both Vpu and Tetherin affect antagonism, but it is not known whether Vpu and Tetherin bind directly to each other. Here, we use cysteine-scanning mutagenesis coupled with oxidation-induced cross-linking to demonstrate that Vpu and Tetherin TMDs bind directly to each other in the membranes of living cells and to map TMD residues that contact each other. We also reveal a property of Vpu, namely the ability to displace Tetherin from sites of viral assembly, which enables Vpu to exhibit residual Tetherin antagonist activity in the absence of surface downregulation or degradation!

Approximately 3% of the world population is infected with hepatitis C virus (HCV), causing a serious public health burden. Like other positive-strand RNA viruses, HCV assembles replicase complexes in association with cellular membranes and produces progeny RNA genomes through negative-strand intermediates. The viral proteins required for RNA replication are nonstructural (NS) proteins NS3 to NS5B. Owing to many obstacles and limitations in structural characterization of proteins and complexes with multiple transmembrane segments, attempts to understand the assembly and action of the HCV replicase complex have been challenging. Nevertheless, great progress has been made in obtaining structural information for several replicase components, providing insights into some aspects of the viral genome replication machinery.

Introduction: Atopic dermatitis (AD) is a common inflammatory skin disease regulated by genetic and environmental factors. Both skin barrier defects and aberrant immune responses are believed to drive cutaneous inflammation in AD. Existing therapies rely largely on allergen avoidance, emollients and topical and systemic immune-suppressants, some with significant toxicity and transient efficacy; no specific targeted therapies are in clinical use today. As our specific understanding of the immune and molecular pathways that cause different subsets of AD increases, a variety of experimental agents, particularly biologic agents that target pathogenic molecules bring the promise of safe and effective therapeutics for long-term use. Areas covered: This paper discusses the molecular pathways characterizing AD, the contributions of barrier and immune abnormalities to its pathogenesis, and development of new treatments that target key molecules in these pathways. In this review, we will discuss a variety of biologic therapies that are in development or in clinical trials for AD, perhaps revolutionizing treatment of this disease. Expert opinion: Biologic agents in moderate to severe AD offer promise for controlling a disease that currently lacks good and safe therapeutics posing a large unmet need. Unfortunately, existing treatments for AD aim to decrease cutaneous inflammation, but are not specific for the pathways driving this disease. An increasing understanding of the immune mechanisms underlying AD brings the promise of narrow targeted therapies as has occurred for psoriasis, another inflammatory skin disease, for which specific biologic agents have been demonstrated to both control the disease and prevent occurrence of new skin lesions. Although no biologic is yet approved for AD, these are exciting times for active therapeutic development in AD that might lead to revolutionary therapeutics for this disease.

This is the first-known quantitative study to measure nursing faculty perceptions of faculty-to-faculty incivility. A total of 588 nursing faculty representing 40 states in the United States participated in the study. Faculty-to-faculty incivility was perceived as a moderate to serious problem. The behaviors reported to be most uncivil included setting a coworker up to fail, making rude remarks or put-downs, and making personal attacks or threatening comments. The most frequently occurring incivilities included resisting change, failing to perform one's share of the workload, distracting others by using media devices during meetings, refusing to communicate on work-related issues, and making rude comments or put-downs. Stress and demanding workloads were two of the factors most likely to contribute to faculty-to-faculty incivility. Fear of retaliation, lack of administrative support, and lack of clear policies were cited as the top reasons for avoiding addressing the prob!

The hepatitis C virus (HCV) NS2 protein has dual roles within the HCV life cycle. While well characterized as an autoprotease that cleaves the NS2/NS3 junction, NS2, primarily via its N-terminal region, is also involved in virion morphogenesis. In order to map the determinants necessary for infectious virus production and gain further insight into the multiple points at which NS2 may impact this process, a detailed mutational analysis of residues spanning amino acids (aa) 1 to 92 was performed. Initial block mutagenesis (5 or 7 amino acid residues) in both bicistronic and monocistronic HCV cell culture-based (HCVcc) genomes revealed that all but two blocks had various levels of impaired infectious virus production. None of these mutations affected RNA replication, indicating that the N-terminal region of NS2 is not required for NS2-3 processing and replicase assembly. Fine mapping identified 29 critical residues that, when mutated, yielded at least a 1 log decrease in inf!

Here we use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated Cas9 endonuclease complexed with dual-RNAs to introduce precise mutations in the genomes of Streptococcus pneumoniae and Escherichia coli. The approach relies on dual-RNA:Cas9-directed cleavage at the targeted genomic site to kill unmutated cells and circumvents the need for selectable markers or counter-selection systems. We reprogram dual-RNA:Cas9 specificity by changing the sequence of short CRISPR RNA (crRNA) to make single- and multinucleotide changes carried on editing templates. Simultaneous use of two crRNAs enables multiplex mutagenesis. In S. pneumoniae, nearly 100% of cells that were recovered using our approach contained the desired mutation, and in E. coli, 65% that were recovered contained the mutation, when the approach was used in combination with recombineering. We exhaustively analyze dual-RNA:Cas9 target requirements to define the range of targetable sequence!

Depression induces structural and functional synaptic plasticity in brain reward circuits, although the mechanisms promoting these changes and their relevance to behavioral outcomes are unknown. Transcriptional profiling of the nucleus accumbens (NAc) for Rho GTPase related genes, which are known regulators of synaptic structure, revealed a sustained reduction in RAS-related C3 botulinum toxin substrate 1 (Rac1) expression after chronic social defeat stress. This was associated with a repressive chromatin state surrounding the proximal promoter of Rac1. Inhibition of class 1 histone deacetylases (HDACs) with MS-275 rescued both the decrease in Rac1 transcription after social defeat stress and depression-related behavior, such as social avoidance. We found a similar repressive chromatin state surrounding the RAC1 promoter in the NAc of subjects with depression, which corresponded with reduced RAC1 transcription. Viral-mediated reduction of Rac1 expression or inhibition of !