Cooperative Interaction of Transcription Termination Factors with the RNA Polymerase II C-terminal Domain

Phosphorylation of the C-terminal domain of RNA polymerase II controls the co-transcriptional assembly of RNA processing and transcription factors. Recruitment relies on conserved CTDinteracting domains that recognize different CTD phosphoisoforms during the transcription cycle, but the molecular basis for their specificity remains unclear. We show that the CTD-interacting domains of two transcription termination factors, Rtt103 and Pcf11, achieve high affinity and specificity both by specifically recognizing the phosphorylated CTD and by cooperatively binding to neighboring CTD repeats. Single amino acid mutations at the protein-protein interface abolish cooperativity and affect recruitment at the 3′-end processing site in vivo. We suggest that this cooperativity provides a signal-response mechanism to ensure that its action is confined only to proper polyadenylation sites where Serine 2 phosphorylation density is highest

The P-Loop Domain of Yeast Clp1 Mediates Interactions Between CF IA and CPF Factors in Pre-mRNA 3′ End Formation

Cleavage factor IA (CF IA), cleavage and polyadenylation factor (CPF), constitute major protein complexes required for pre-mRNA 3′ end formation in yeast. The Clp1 protein associates with Pcf11, Rna15 and Rna14 in CF IA but its functional role remained unclear. Clp1 carries an evolutionarily conserved P-loop motif that was previously shown to bind ATP. Interestingly, human and archaean Clp1 homologues, but not the yeast protein, carry 5′ RNA kinase activity. We show that depletion of Clp1 in yeast promoted defective 3′ end formation and RNA polymerase II termination; however, cells expressing Clp1 with mutant P-loops displayed only minor defects in gene expression. Similarly, purified and reconstituted mutant CF IA factors that interfered with ATP binding complemented CF IA depleted extracts in coupled in vitro transcription/3′ end processing reactions. We found that Clp1 was required to assemble recombinant CF IA and that certain P-loop mutants failed to interact with the CF IA subunit Pcf11. In contrast, mutations in Clp1 enhanced binding to the 3′ endonuclease Ysh1 that is a component of CPF. Our results support a structural role for the Clp1 P-loop motif. ATP binding by Clp1 likely contributes to CF IA formation and cross-factor interactions during the dynamic process of 3′ end formation

Trophic Shifts of a Generalist Consumer in Response to Resource Pulses

Trophic shifts of generalist consumers can have broad food-web and biodiversity consequences through altered trophic flows and vertical diversity. Previous studies have used trophic shifts as indicators of food-web responses to perturbations, such as species invasion, and spatial or temporal subsidies. Resource pulses, as a form of temporal subsidies, have been found to be quite common among various ecosystems, affecting organisms at multiple trophic levels. Although diet switching of generalist consumers in response to resource pulses is well documented, few studies have examined if the switch involves trophic shifts, and if so, the directions and magnitudes of the shifts. In this study, we used stable carbon and nitrogen isotopes with a Bayesian multi-source mixing model to estimate proportional contributions of three trophic groups (i.e. producer, consumer, and fungus-detritivore) to the diets of the White-footed mouse (Peromyscus leucopus) receiving an artificial seed pulse or a naturally-occurring cicadas pulse. Our results demonstrated that resource pulses can drive trophic shifts in the mice. Specifically, the producer contribution to the mouse diets was increased by 32% with the seed pulse at both sites examined. The consumer contribution to the mouse diets was also increased by 29% with the cicadas pulse in one of the two grids examined. However, the pattern was reversed in the second grid, with a 13% decrease in the consumer contribution with the cicadas pulse. These findings suggest that generalist consumers may play different functional roles in food webs under perturbations of resource pulses. This study provides one of the few highly quantitative descriptions on dietary and trophic shifts of a key consumer in forest food webs, which may help future studies to form specific predictions on changes in trophic interactions following resource pulses

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce

Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies

) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification. (sister taxon to Phalacrocoracidae). These relationships are invariant when ‘backbone’ constraints based on recent avian phylogenies are imposed.Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several “stem fossil + crown family” clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √ s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Search for resonant production of dark quarks in the dijet final state with the ATLAS detector

This paper presents a search for a new Z′ resonance decaying into a pair of dark quarks which hadronise into dark hadrons before promptly decaying back as Standard Model particles. This analysis is based on proton-proton collision data recorded at $$\sqrt{s}$$ s = 13 TeV with the ATLAS detector at the Large Hadron Collider between 2015 and 2018, corresponding to an integrated luminosity of 139 fb−1. After selecting events containing large-radius jets with high track multiplicity, the invariant mass distribution of the two highest-transverse-momentum jets is scanned to look for an excess above a data-driven estimate of the Standard Model multijet background. No significant excess of events is observed and the results are thus used to set 95% confidence-level upper limits on the production cross-section times branching ratio of the Z′ to dark quarks as a function of the Z′ mass for various dark-quark scenarios

Study of High-Transverse-Momentum Higgs Boson Production in Association with a Vector Boson in the qqbb Final State with the ATLAS Detector

This Letter presents the first study of Higgs boson production in association with a vector boson (V = W or Z) in the fully hadronic qqbb final state using data recorded by the ATLAS detector at the LHC in proton-proton collisions at √s = 13 TeV and corresponding to an integrated luminosity of 137fb^{-1}. The vector bosons and Higgs bosons are each reconstructed as large-radius jets and tagged using jet substructure techniques. Dedicated tagging algorithms exploiting b-tagging properties are used to identify jets consistent with Higgs bosons decaying into b¯b. Dominant backgrounds from multijet production are determined directly from the data, and a likelihood fit to the jet mass distribution of Higgs boson candidates is used to extract the number of signal events. The VH production cross section is measured inclusively and differentially in several ranges of Higgs boson transverse momentum: 250–450, 450–650, and greater than 650 GeV. The inclusive signal yield relative to the standard model expectation is observed to be μ = 1.4 ^{+1.0}_{-0.9} and the corresponding cross section is 3.1 ± 1.3(stat.)^{+1.8}_{-1.4}(syst) pb

Search for new phenomena with top-quark pairs and large missing transverse momentum using 140 fb−1 of pp collision data at \sqrt{s} = 13 TeV with the ATLAS detector

A search is conducted for new phenomena in events with a top quark pair and large missing transverse momentum, where the top quark pair is reconstructed in final states with one isolated electron or muon and multiple jets. The search is performed using the Large Hadron Collider proton-proton collision data sample at a centre-of-mass energy of \sqrt{s} = 13 TeV recorded by the ATLAS detector that corresponds to an integrated luminosity of 140 fb^{−1}. An analysis based on neural network classifiers is optimised to search for directly produced pairs of supersymmetric partners of the top quark (stop), and to search for spin-0 mediators, produced in association with a pair of top quarks, that decay into dark-matter particles. In the stop search, the analysis is designed to target models in which the mass difference between the stop and the neutralino from the stop decay is close to the top quark mass. This new search is combined with previously published searches in final states with different lepton multiplicities. No significant excess above the Standard Model background is observed, and limits at 95% confidence level are set. Models with neutralinos with masses up to 570 GeV are excluded, while for small neutralino masses models are excluded for stop masses up to 1230 GeV. Scalar (pseudoscalar) dark matter mediator masses as large as 350 (370) GeV are excluded when the coupling strengths of the mediator to Standard Model and dark-matter particles are both set to one. At lower mediator masses, models with production cross-sections as small as 0.15 (0.16) times the nominal predictions are excluded. Results of this search are also used to set constraints on effective four-fermion contact interactions between top quarks and neutrinos