TY - JOUR A1 - Maurer, Jana A1 - Hupp, Sabrina A1 - Bischoff, Carolin A1 - Foertsch, Christina A1 - Mitchell, Timothy J. A1 - Chakraborty, Trinad A1 - Iliev, Asparouh I. T1 - Distinct neurotoxicity profile of listeriolysin O from \(Listeria\) \(monocytogenes\) JF - Toxins N2 - Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, \(Streptococcus\) \(pneumoniae\) and \(Listeria\) \(monocytogenes\), cause fatal bacterial meningitis, and both produce toxins of the CDC family—pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death. We utilized primary glial cultures and acute mouse brain slices to examine the neuropathological effects of listeriolysin O and to compare it to pneumolysin with identical hemolytic activity. In cultures, listeriolysin O permeabilized cells slower than pneumolysin did but still initiated non-lytic astrocytic cell shape changes, just as pneumolysin did. In an acute brain slice culture system, listeriolysin O produced dendritic varicosities in an NMDA-dependent manner but failed to cause dendritic spine collapse and cortical astrocyte reorganization. Thus, listeriolysin O demonstrated slower cell permeabilization and milder glial cell remodeling ability than did pneumolysin and lacked dendritic spine collapse capacity but exhibited equivalent dendritic pathology. KW - medicine KW - listeriolysin O KW - meningitis KW - acute slices KW - variocosities KW - dendritic spines Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172130 VL - 9 IS - 1 ER - TY - JOUR T1 - Search for a scalar partner of the top quark in the jets plus missing transverse momentum final state at \(\sqrt{s}\) = 13 TeV with the ATLAS detector JF - Journal of High Energy Physics N2 - A search for pair production of a scalar partner of the top quark in events with four or more jets plus missing transverse momentum is presented. An analysis of 36.1 fb\(^{−1}\) of \(\sqrt{s}\) = 13 TeV proton-proton collisions collected using the ATLAS detector at the LHC yields no significant excess over the expected Standard Model background. To interpret the results a simplified supersymmetric model is used where the top squark is assumed to decay via \(\tilde{t}_1\) → \(t^{(∗)}\)\(\tilde{χ}^0_1\) and \(\tilde{t}_1\) → \(b\tilde{χ}^±_1\) → \({bW}^{(∗)}\tilde{χ}^0_1\), where \(\tilde{χ}^0_1\) (\(\tilde{χ}^±_1\)) denotes the lightest neutralino (chargino). Exclusion limits are placed in terms of the top-squark and neutralino masses. Assuming a branching ratio of 100% to \(t\tilde{χ}^0_1\), top-squark masses in the range 450–1000 GeV are excluded for \(\tilde{χ}^0_1\) masses below 160 GeV. In the case where \(m_{\tilde{t}_1}\) ∼ \(m_t\) + \(m_{\tilde{χ}^0_1}\), top-squark masses in the range 235–590 GeV are excluded. KW - high energy physics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172161 VL - 12 ER - TY - JOUR T1 - All-sky search for high-energy neutrinos from gravitational wave event GW170104 with the ANTARES neutrino telescope JF - European Physical Journal C N2 - Advanced LIGO detected a significant gravitational wave signal (GW170104) originating from the coalescence of two black holes during the second observation run on January 4th, 2017. An all-sky high-energy neutrino follow-up search has been made using data from the Antares neutrino telescope, including both upgoing and downgoing events in two separate analyses. No neutrino candidates were found within ±500 s around the GW event time nor any time clustering of events over an extended time window of ±3 months. The non-detection is used to constrain isotropic-equivalent high-energy neutrino emission from GW170104 to less than ∼ 1.2 × \(10^{55}\) erg for a \(E^{−2}\) spectrum. This constraint is valid in the energy range corresponding to the 5–95% quantiles of the neutrino flux [3.2 TeV; 3.6 PeV], if the GW emitter was below the Antares horizon at the alert time. KW - high energy physics KW - high energy neutrinos KW - neutrino telescope KW - neutrino emission KW - neutrino flux Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172174 VL - 77 ER - TY - JOUR T1 - Measurement of the Drell-Yan triple-differential cross section in \(pp\) collisions at \(\sqrt{s}\) = 8 TeV JF - Journal of High Energy Physics N2 - This paper presents a measurement of the triple-differential cross section for the Drell-Yan process \({Z/γ^*}\) → ℓ\(^+\)ℓ\(^-\) where ℓ is an electron or a muon. The measurement is performed for invariant masses of the lepton pairs, \(m_{ℓℓ}\) , between 46 and 200 GeV using a sample of 20.2 fb\(^{−1}\) of \(pp\) collisions data at a centre-of-mass energy of \(\sqrt{s}\) = 8 TeV collected by the ATLAS detector at the LHC in 2012. The data are presented in bins of invariant mass, absolute dilepton rapidity, |\(y_{ℓℓ}\)|, and the angular variable cos \(θ^*\) between the outgoing lepton and the incoming quark in the Collins-Soper frame. The measurements are performed in the range |\(y_{ℓℓ}\)| < 2.4 in the muon channel, and extended to |\(y_{ℓℓ}\)| < 3.6 in the electron channel. The cross sections are used to determine the \(Z\) boson forward-backward asymmetry as a function of |\(y_{ℓℓ}\)| and \(m_{ℓℓ}\) . The measurements achieve high-precision, below the percent level in the pole region, excluding the uncertainty in the integrated luminosity, and are in agreement with predictions. These precision data are sensitive to the parton distribution functions and the effective weak mixing angle. KW - high energy physics KW - Hadron-Hadron scattering (experiments) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172204 VL - 59 ER - TY - JOUR T1 - Evidence for the \(H\) → \({b\overline{b}}\) decay with the ATLAS detector JF - Journal of High Energy Physics N2 - A search for the decay of the Standard Model Higgs boson into a \({b\overline{b}}\) pair when produced in association with a \(W\) or \(Z\) boson is performed with the ATLAS detector. The analysed data, corresponding to an integrated luminosity of 36.1 fb\(^{−1}\), were collected in proton-proton collisions in Run 2 of the Large Hadron Collider at a centre-of-mass energy of 13 TeV. Final states containing zero, one and two charged leptons (electrons or muons) are considered, targeting the decays \(Z\) → \({νν}\), \(W\) → \({ℓν}\) and \(Z\) → \({ℓℓ}\). For a Higgs boson mass of 125 GeV, an excess of events over the expected background from other Standard Model processes is found with an observed significance of 3.5 standard deviations, compared to an expectation of 3.0 standard deviations. This excess provides evidence for the Higgs boson decay into b-quarks and for its production in association with a vector boson. The combination of this result with that of the Run 1 analysis yields a ratio of the measured signal events to the Standard Model expectation equal to 0.90 ± 0.18(stat.)\(^{+0.21}_{−0.19}\)(syst.). Assuming the Standard Model production cross-section, the results are consistent with the value of the Yukawa coupling to \(b\)-quarks in the Standard Model. KW - High energy physics KW - Hadron-Hadron scattering (experiments) KW - Higgs physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172216 VL - 24 ER - TY - JOUR A1 - Schönegge, Anne-Marie A1 - Gallion, Jonathan A1 - Picard, Louis-Philippe A1 - Wilkins, Angela D. A1 - Le Gouill, Christian A1 - Audet, Martin A1 - Stallaert, Wayne A1 - Lohse, Martin J. A1 - Kimmel, Marek A1 - Lichtarge, Olivier A1 - Bouvier, Michel T1 - Evolutionary action and structural basis of the allosteric switch controlling β\(_2\)AR functional selectivity JF - Nature Communications N2 - Functional selectivity of G-protein-coupled receptors is believed to originate from ligand-specific conformations that activate only subsets of signaling effectors. In this study, to identify molecular motifs playing important roles in transducing ligand binding into distinct signaling responses, we combined in silico evolutionary lineage analysis and structure-guided site-directed mutagenesis with large-scale functional signaling characterization and non-negative matrix factorization clustering of signaling profiles. Clustering based on the signaling profiles of 28 variants of the β\(_2\)-adrenergic receptor reveals three clearly distinct phenotypical clusters, showing selective impairments of either the Gi or βarrestin/endocytosis pathways with no effect on Gs activation. Robustness of the results is confirmed using simulation-based error propagation. The structural changes resulting from functionally biasing mutations centered around the DRY, NPxxY, and PIF motifs, selectively linking these micro-switches to unique signaling profiles. Our data identify different receptor regions that are important for the stabilization of distinct conformations underlying functional selectivity. KW - toxicology KW - functional clustering KW - molecular modelling KW - protein design KW - receptor pharmacology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172268 VL - 8 ER - TY - JOUR T1 - Analysis of the Wtb vertex from the measurement of triple-differential angular decay rates of single top quarks produced in the \(t\)-channel at \(\sqrt{s}\) = 8 TeV with the ATLAS detector JF - Journal or High Energy Physics N2 - The electroweak production and subsequent decay of single top quarks in the \(t\)-channel is determined by the properties of the \({Wtb}\) vertex, which can be described by the complex parameters of an effective Lagrangian. An analysis of a triple-differential decay rate in \(t\)-channel production is used to simultaneously determine five generalised helicity fractions and phases, as well as the polarisation of the produced top quark. The complex parameters are then constrained. This analysis is based on 20.2 fb\(^{−1}\) of proton-proton collision data at a centre-of-mass energy of 8 TeV collected with the ATLAS detector at the LHC. The fraction of decays containing transversely polarised \(W\) bosons is measured to be \(f_1\) = 0.30 ± 0.05. The phase between amplitudes for transversely and longitudinally polarised \(W\) bosons recoiling against left-handed \(b\)-quarks is measured to be \(\delta\)_ = 0.002\(\pi^{+0.016\pi}_{+0.017\pi}\), giving no indication of CP violation. The fractions of longitudinal or transverse \(W\) bosons accompanied by right-handed \(b\)-quarks are also constrained. Based on these measurements, limits are placed at 95% CL on the ratio of the complex coupling parameters Re [\({g_R/V_L}\) \(\in\) [−0.12, 0.17] and Im [\({g_R/V_L}\) \(\in\) [−0.07, 0.06]. Constraints are also placed on the ratios |\({V_R}/{V_L}\)| and |\({g_L}/{V_L}\)|. In addition, the polarisation of single top quarks in the \(t\)-channel is constrained to be \(P\) > 0.72 (95% CL). None of the above measurements make assumptions about the value of any of the other parameters or couplings and all of them are in agreement with the Standard Model. KW - High energy physics KW - Electroweak interaction KW - Hadron-Hadron scattering (experiments) KW - Top physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172310 VL - 2017 IS - 17 ER - TY - JOUR A1 - Mende, Daniel R. A1 - Letunic, Ivica A1 - Huerta-Cepas, Jaime A1 - Li, Simone S. A1 - Forslund, Kristoffer A1 - Sunagawa, Shinichi A1 - Bork, Peer T1 - proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes JF - Nucleic Acids Research N2 - The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de. KW - biology KW - genomic sequence KW - prokaryotic clade KW - proGenomes KW - habitat information KW - taxonomic description KW - genome collection KW - comparative genomics KW - genomics research Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171987 VL - 45 IS - D1 ER - TY - JOUR A1 - Elsässer, S. A1 - Schiebl, M. A1 - Mukhin, A. A. A1 - Balbashov, A. M. A1 - Pimenov, A. A1 - Geurts, J. T1 - Impact of temperature-dependent local and global spin order in \(R\)MnO\(_3\) compounds for spin-phonon coupling and electromagnon activity JF - New Journal of Physics N2 - The orthorhombic rare-earth manganite compounds \(R\)MnO\(_3\) show a global magnetic order for \(T\) < \(T\)\(_N\), and several representatives are multiferroic with a cycloidal spin ground state order for \(T\) < \(T\)\(_c\)\(_y\)\(_c\)\(_l\) < \(T\)\(_N\) \(\approx\) 40 K. We deduce from the temperature dependence of spin–phonon coupling in Raman spectroscopy for a series of \(R\)MnO\(_3\) compounds that their spin order locally persists up to about twice \(T\)\(_N\). Along the same line, our observation of the persistence of the electromagnon in GdMnO\(_3\) up to \(T\) \(\approx\) 100 K is attributed to a local cycloidal spin order for \(T\) > \(T\)\(_c\)\(_y\)\(_c\)\(_l\), in contrast to the hitherto assumed incommensurate sinusoidal phase in the intermediate temperature range. The development of the magnetization pattern can be described in terms of an order–disorder transition at \(T\)\(_c\)\(_y\)\(_c\)\(_l\) within a pseudospin model of localized spin cycloids with opposite chirality. KW - physics KW - RMnO3 KW - multiferroics KW - electromagnon KW - Raman spectroscopy KW - spin-phonon coupling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171978 VL - 19 ER - TY - JOUR A1 - Jannasch, Maren A1 - Weigel, Tobias A1 - Engelhardt, Lisa A1 - Wiezoreck, Judith A1 - Gaetzner, Sabine A1 - Walles, Heike A1 - Schmitz, Tobias A1 - Hansmann, Jan T1 - \({In}\) \({vitro}\) chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction JF - ALTEX - Alternatives to Animal Experimentation N2 - Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned \({in}\) \({vitro}\) test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages. Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of biomaterial-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous \({in}\) \({vitro}\) tissue models. A high correlation of the \({in}\) \({vitro}\) tissue model to state of the art \({in}\) \({vivo}\) study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction. KW - medicine KW - foreign body reaction KW - fibroblast chemotaxis KW - tissue remodeling KW - in vitro KW - quanititative characterization Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172080 VL - 34 IS - 2 ER -