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We present a measurement of the W-boson-pair production cross section in p (p) over bar collisions at 1.96 TeV center-of-mass energy and the first measurement of the differential cross section as a function of jet multiplicity and leading-jet energy. The W+W- cross section is measured in the final state comprising two charged leptons and neutrinos, where either charged lepton can be an electron or a muon. Using data collected by the CDF experiment corresponding to 9.7 fb(-1) of integrated luminosity, a total of 3027 collision events consistent with W+W- production are observed with an estimated background contribution of 1790 +/- 190 events. The measured total cross section is sigma(p (p) over bar --> W+W-) = 14.0 +/- 0.6(stat)(-1.0)(+1.2)(syst) +/- 0.8(lumi) pb, consistent with the standard model prediction.

A search is performed for a vector-like heavy T quark that is produced in pairs and that decays to a top quark and a Higgs boson. The data analysed correspond to an integrated luminosity of 19.7 fb(-1) collected with the CMS detector in proton-proton collisions at root s = 8TeV. For T quarks with large mass values the top quarks and Higgs bosons can have significant Lorentz boosts, so that their individual decay products often overlap and merge. Methods are applied to resolve the substructure of such merged jets. Upper limits on the production cross section of a T quark with mass between 500 and 1000 GeV/c(2) are derived. If the T quark decays exclusively to tH, the observed (expected) lower limit on the mass of the T quark is 745 (773) GeV/c(2) at 95% confidence level. For the first time an algorithm is used for tagging boosted Higgs bosons that is based on a combination of jet substructure information and b tagging.

Transposable elements comprise roughly 40% of mammalian genomes(1). They have an active role in genetic variation, adaptation and evolution through the duplication or deletion of genes or their regulatory elements(2-4), and transposable elements themselves can act as alternative promoters for nearby genes, resulting in noncanonical regulation of transcription(5,6). However, transposable element activity can lead to detrimental genome instability(7), and hosts have evolved mechanisms to silence transposable element mobility appropriately(8,9). Recent studies have demonstrated that a subset of transposable elements, endogenous retroviral elements (ERVs) containing long terminal repeats (LTRs), are silenced through trimethylation of histone H3 on lysine 9 (H3K9me3) by ESET (also known as SETDB1 or KMT1E)(10) and a co-repressor complex containing KRAB-associated protein 1 (KAP1; also known as TRIM28)(11) in mouse embryonic stem cells. Here we show that the replacement histone variant H3.3 is enriched at class I and class II ERVs, notably those of the early transposon (ETn)/MusD family and intracisternal A-type particles (IAPs). Deposition at a subset of these elements is dependent upon the H3.3 chaperone complex containing alpha-thalassaemia/mental retardation syndrome X-linked (ATRX) 12 and death-domain-associated protein (DAXX)(12-14). We demonstrate that recruitment of DAXX, H3.3 and KAP1 to ERVs is co-dependent and occurs upstream of ESET, linking H3.3 to ERV-associated H3K9me3. Importantly, H3K9me3 is reduced at ERVs upon H3.3 deletion, resulting in derepression and dysregulation of adjacent, endogenous genes, along with increased retrotransposition of IAPs. Our study identifies a unique heterochromatin state marked by the presence of both H3.3 and H3K9me3, and establishes an important role for H3.3 in control of ERV retrotransposition in embryonic stem cells.

Gene expression is highly regulated at the step of transcription initiation, and transcription activators play a critical role in this process. RbpA, an actinobacterial transcription activator that is essential in Mycobacterium tuberculosis (Mtb), binds selectively to group 1 and certain group 2 sigma-factors. To delineate the molecular mechanism of RbpA, we show that the Mtb RbpA sigma-interacting domain (SID) and basic linker are sufficient for transcription activation. We also present the crystal structure of the Mtb RbpA-SID in complex with domain 2 of the housekeeping sigma-factor, sigma(A). The structure explains the basis of sigma-selectivity by RbpA, showing that RbpA interacts with conserved regions of sigma(A) as well as the nonconserved region (NCR), which is present only in housekeeping sigma-factors. Thus, the structure is the first, to our knowledge, to show a protein interacting with the NCR of a sigma-factor. We confirm the basis of selectivity and the observed interactions using mutagenesis and functional studies. In addition, the structure allows for a model of the RbpA-SID in the context of a transcription initiation complex. Unexpectedly, the structural modeling suggests that RbpA contacts the promoter DNA, and we present in vivo and in vitro studies supporting this finding. Our combined data lead to a better understanding of the mechanism of RbpA function as a transcription activator.

The cholecystokinin receptor type 1 (CCK1R) is a G protein-coupled receptor ( GPCR) that is involved in several biological processes including the regulation of the secretion of digestive enzymes. The peptide hormone cholecystokinin (CCK) binds to CCK1R, which is an important pharmacological target for several diseases, including obesity. Interestingly, nutritional dietary peptides also appear to activate CCK1R, and may play a role in CCK1R signaling in the gut. In this study, a novel technique to screen for CCK1R ligands based on affinity-selection is described. Functional expressed CCK1R is reconstituted into membrane nanoparticles called NABBs (nanoscale apo-lipoprotein bound bilayers). NABBs are native-like bilayer membrane systems for incorporation of GPCRs. CCK1R-NABB5 were characterized using a fluorescently labeled CCK analog and can be used as a cutting-edge technology to screen for CCK1R ligands using affinity-selection mass spectrometry. (C) 2014 Elsevier Inc. All rights reserved.

A search is presented for quark contact interactions and extra spatial dimensions in proton-proton collisions at root s = 8 TeV using dijet angular distributions. The search is based on a data set corresponding to an integrated luminosity of 19.7 fb(-1) collected by the CMS detector at the CERN LHC. Dijet angular distributions are found to be in agreement with the perturbative QCD predictions that include electroweak corrections. Limits on the contact interaction scale from a variety of models at next-to-leading order in QCD corrections are obtained. A benchmark model in which only left-handed quarks participate is excluded up to a scale of 9.0 (11.7) TeV for destructive (constructive) interference at 95% confidence level. Lower limits between 5.9 and 8.4 TeV on the scale of virtual graviton exchange are extracted for the Arkani-Hamed-Dimopoulos-Dvali model of extra spatial dimensions. (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.

The first measurement of the cross section ratio sigma(t (t) over barb (b) over bar)/sigma(t (t) over bar jj) is presented using a data sample corresponding to an integrated luminosity of 19.6 fb(-1) collected in pp collisions at root s = 8 TeV with the CMS detector at the LHC. Events with two leptons (e or mu) and four reconstructed jets, including two identified as b quark jets, in the final state are selected. The ratio is determined for a minimum jet transverse momentum p(T) of both 20 and 40 GeV/c. The measured ratio is 0.022 +/- 0.003 (stat) +/- 0.005 (syst) for p(T) > 20GeV/c. The absolute cross sections sigma(t (t) over barb (b) over bar) and sigma(t (t) over bar jj) are also measured. The measured ratio for p(T) > 40 GeV/c is compatible with a theoretical quantum chromodynamics calculation at next-to-leading order. (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.

Stress plays a substantial role in shaping behavior and brain function, often with lasting effects. How these lasting effects occur in the context of a fixed postmitotic neuronal genome has been an enduring question for the field. Synaptic plasticity and neurogenesis have provided some of the answers to this question, and more recently epigenetic mechanisms have come to the fore. The exploration of epigenetic mechanisms recently led us to discover that a single acute stress can regulate the expression of retrotransposons in the rat hippocampus via an epigenetic mechanism. We propose that this response may represent a genomic stress response aimed at maintaining genomic and transcriptional stability in vulnerable brain regions such as the hippocampus. This finding and those of other researchers have made clear that retrotransposons and the genomic plasticity they permit play a significant role in brain function during stress and disease. These observations also raise the possibility that the transposome might have adaptive functions at the level of both evolution and the individual organism.

Social insects present highly interesting and experimentally amenable systems for the study of disease transmission because they naturally live in dense groups of frequently interacting individuals. Using experimental inoculations of five trypanosomatid strains into groups of its natural host, the bumblebee Bombus terrestris, we investigate the effects of the initial parasite strain distribution across group members on the establishment and transmission success of the different strains to new hosts. For a given number of parasite strains circulating within a host group, transmission to new hosts was increased when the strains were initially inoculated as mixed infections (as opposed to separate single infections), presumably because mixed infections generally favored fast replicating strains. In contrast, separate single infections reduced transmission at least in part through a precedence effect, whereby weak strains appeared to persist by making their host unavailable to superinfection. These results suggest that host groups could benefit from 'compartmentalizing' infections by different parasite strains across different group members, which might be achieved in social insects, for example, by division of labor. (C) 2015 Elsevier B.V. All rights reserved.

Objectives: Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide and new antimicrobials are urgently needed. Our aim was new chimeric phage endolysins, or lysins, with improved bactericidal activity by swapping the structural components of two pneumococcal phage lysozymes: Cpl-1 (the best lysin tested to date) and Cpl-7S. Methods: The bactericidal effects of four new chimeric lysins were checked against several bacteria. The purified enzymes were added at different concentrations to resuspended bacteria and viable cells were measured after 1 h. Killing capacity of the most active lysin, Cpl-711, was tested in a mouse bacteraemia model, following mouse survival after injecting different amounts (25-500 mu g) of enzyme. The capacity of Cpl-711 to reduce pneumococcal biofilm formation was also studied. Results: The chimera Cpl-711 substantially improved the killing activity of the parental phage lysozymes, Cpl-1 and Cpl-7S, against pneumococcal bacteria, including multiresistant strains. Specifically, 5 mu g/mL Cpl-711 killed >= 7.5 log of pneumococcal R6 strain. Cpl-711 also reduced pneumococcal biofilm formation and killed 4 log of the bacterial population at 1 mu g/mL. Mice challenged intraperitoneally with D39_IU pneumococcal strain were protected by treatment with a single intraperitoneal injection of Cpl-711 1 h later, resulting in about 50% greater protection than with Cpl-1. Conclusions: Domain swapping among phage lysins allows the construction of new chimeric enzymes with high bactericidal activity and a different substrate range. Cpl-711, the most powerful endolysin against pneumococci, offers a promising therapeutic perspective for the treatment of multiresistant pneumococcal infections.