6,256 research outputs found

    Large-scale and significant expression from pseudogenes in Sodalis glossinidius – a facultative bacterial endosymbiont

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    The majority of bacterial genomes have high coding efficiencies, but there are some genomes of intracellular bacteria that have low gene density. The genome of the endosymbiont Sodalis glossinidius contains almost 50 % pseudogenes containing mutations that putatively silence them at the genomic level. We have applied multiple ‘omic’ strategies, combining Illumina and Pacific Biosciences Single-Molecule Real-Time DNA sequencing and annotation, stranded RNA sequencing and proteome analysis to better understand the transcriptional and translational landscape of Sodalis pseudogenes, and potential mechanisms for their control. Between 53 and 74 % of the Sodalis transcriptome remains active in cell-free culture. The mean sense transcription from coding domain sequences (CDSs) is four times greater than that from pseudogenes. Comparative genomic analysis of six Illumina-sequenced Sodalis isolates from different host Glossina species shows pseudogenes make up ~40 % of the 2729 genes in the core genome, suggesting that they are stable and/or that Sodalis is a recent introduction across the genus Glossina as a facultative symbiont. These data shed further light on the importance of transcriptional and translational control in deciphering host–microbe interactions. The combination of genomics, transcriptomics and proteomics gives a multidimensional perspective for studying prokaryotic genomes with a view to elucidating evolutionary adaptation to novel environmental niches

    NuSTAR Tests of Sterile-Neutrino Dark Matter: New Galactic Bulge Observations and Combined Impact

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    We analyze two dedicated NuSTAR observations with exposure ∼190{\sim}190 ks located ∼10∘{\sim}10^\circ from the Galactic plane, one above and the other below, to search for x-ray lines from the radiative decay of sterile-neutrino dark matter. These fields were chosen to minimize astrophysical x-ray backgrounds while remaining near the densest region of the dark matter halo. We find no evidence of anomalous x-ray lines in the energy range 5--20 keV, corresponding to sterile neutrino masses 10--40 keV. Interpreted in the context of sterile neutrinos produced via neutrino mixing, these observations provide the leading constraints in the mass range 10--12 keV, improving upon previous constraints in this range by a factor ∼2{\sim}2. We also compare our results to Monte Carlo simulations, showing that the fluctuations in our derived limit are not dominated by systematic effects. An updated model of the instrumental background, which is currently under development, will improve NuSTAR's sensitivity to anomalous x-ray lines, particularly for energies 3--5 keV.Comment: 16 pages, 5 figures. Text updated to match published version in PRD. Conclusions unchange

    Report of the NAFO Joint Commission-Scientific Council Working Group on Ecosystem Approach Framework to Fisheries Management (WG-EAFFM) Meeting

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    1. Opening by the co-Chairs, Robert Day (Canada) and Andrew Kenny (EU) 2. Appointment of Rapporteur 3. Adoption of Agenda 4. SC response to FC requests for advice: a. Consideration of 2014 SC advice regarding extent of the New England and Corner Rise Seamounts (Annex 13 of FC Doc. 16-20) b. Risk assessment of scientific surveys impact on VME in closed areas (2016 FC Request to SC #3) 5. Discussion of ongoing matters: a. Assessment of NAFO bottom fisheries SAI (2016 FC Request to SC # 6) b. Progress of analysis undertaken by EU NEREIDA funded research project c. Update on identification and mapping of sensitive species and habitats in the NAFO area d. Further development and application of the Ecosystems Approach to Fisheries (EAF) Roadmap, including further consideration of any issues raised at the Scientific Council Meeting, 01-15 June 2017 e. Alfonsino fishery on seamounts in the NAFO Regulatory Area. 6. Recommendations to forward to the Commission and Scientific Council 7. Other Matters a. Presentation: Canada’s Marine Conservation targets for 2017 and 2020: The Role of Fisheries b. NAFO Working Group on Improving Efficiency of NAFO Working Group Process c. Recommendation for a new co-Chair d. Timely availability of meeting reports 8. Adoption of Report 9. Adjournmen

    Low self-control promotes the willingness to sacrifice in close relationships

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    Although previous theories and research have suggested that human behavior is automatically driven by selfish impulses (e.g., vengeance rather than forgiveness), the present research tested the hypothesis that in close relationships, people's impulsive inclination is to be prosocial and to sacrifice for their partner-to pursue the interests of the partner or of the relationship at some costs for the self. Results from four studies demonstrated that people with low self-control, relative to those with high self-control, reported greater willingness to sacrifice for their close others. Furthermore, Study 4 demonstrated that communal orientation was more strongly associated with sacrifice among participants with low self-control than participants with high self-control. This moderational pattern supports the hypothesis that communal orientation functions as a default approach to sacrifice in the context of close relationships. Taken together, these findings suggest that under certain crucial conditions in close relationships, gut-level impulses are more likely than deliberative considerations to promote prorelationship behavior. © The Author(s) 2013

    Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

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    Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

    Hercules X-1: Pulsed gamma-rays detected above 150 GeV

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    The 1.24 second binary pulsar Her X-1, first observed in X-rays in 1971 by UHURU has now been seen as a sporadic gamma ray source from 1 TeV up to at least 500 TeV. In addition, reprocessed optical and infrared pulses are seen from the companion star HZ Herculis. Thus measurements of the Her X-1/HZ Herculis system span 15 decades in energy, rivaling both the Crab pulsar and Cygnus X-3 in this respect for a discrete galactic source

    GeV-Scale Thermal WIMPs: Not Even Slightly Dead

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    Weakly Interacting Massive Particles (WIMPs) have long reigned as one of the leading classes of dark matter candidates. The observed dark matter abundance can be naturally obtained by freezeout of weak-scale dark matter annihilations in the early universe. This "thermal WIMP" scenario makes direct predictions for the total annihilation cross section that can be tested in present-day experiments. While the dark matter mass constraint can be as high as mχ≳100m_\chi\gtrsim100 GeV for particular annihilation channels, the constraint on the total cross section has not been determined. We construct the first model-independent limit on the WIMP total annihilation cross section, showing that allowed combinations of the annihilation-channel branching ratios considerably weaken the sensitivity. For thermal WIMPs with s-wave 2→22\rightarrow2 annihilation to visible final states, we find the dark matter mass is only known to be mχ≳20m_\chi\gtrsim20 GeV. This is the strongest largely model-independent lower limit on the mass of thermal-relic WIMPs, together with the upper limit on the mass from the unitarity bound (mχ≲100m_\chi\lesssim 100 TeV), it defines what we call the "WIMP window". To probe the remaining mass range, we outline ways forward.Comment: 16 pages, 10 figures, references added, accepted for publication in PR

    Neutron Capture Cross Sections for the Weak s Process

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    In past decades a lot of progress has been made towards understanding the main s-process component that takes place in thermally pulsing Asymptotic Giant Branch (AGB) stars. During this process about half of the heavy elements, mainly between 90<=A<=209 are synthesized. Improvements were made in stellar modeling as well as in measuring relevant nuclear data for a better description of the main s process. The weak s process, which contributes to the production of lighter nuclei in the mass range 56<=A<=90 operates in massive stars (M>=8Msolar) and is much less understood. A better characterization of the weak s component would help disentangle the various contributions to element production in this region. For this purpose, a series of measurements of neutron-capture cross sections have been performed on medium-mass nuclei at the 3.7-MV Van de Graaff accelerator at FZK using the activation method. Also, neutron captures on abundant light elements with A<56 play an important role for s-process nucleosynthesis, since they act as neutron poisons and affect the stellar neutron balance. New results are presented for the (n,g) cross sections of 41K and 45Sc, and revisions are reported for a number of cross sections based on improved spectroscopic information

    TNF Receptor-Associated Factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets.

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    Background: Reactive oxygen species generation is one consequence of ligand engagement of platelet glycoprotein (GP) receptors GPIb-IX-V and GPVI, which bind VWF/collagen and initiate thrombosis at arterial shear, however the precise molecular mechanism coupling redox pathway activation to engagement of these receptors is unknown. Objective: The objective of this study was to identify novel binding partners for GPIb-IX-V and GPVI that could provide a potential link between redox pathways and early platelet signalling events. Methods and Results: Using protein array analysis and affinity-binding assays, we demonstrated that the orphan TNF receptor-associated factor (TRAF) family member, TRAF4, selectively binds cytoplasmic sequences of GPIbβ and GPVI. TRAF4, p47(phox) (of the NADPH oxidase (Nox2) enzyme complex), and other redox relevant signalling proteins such as Hic-5, co-immunoprecipitate with GPIb/GPVI from human platelet lysates whilst MBP-TRAF4 or MBP-p47(phox) fusion proteins specifically pull-down GPIb/GPVI. GPIb- or GPVI-selective agonists induce phosphorylation of the TRAF4-associated proteins, Hic-5 and Pyk2, with phosphorylation attenuated by Nox2 inhibition. Conclusion: These results describe the first direct association of TRAF4 with a receptor, and identify a novel binding partner for GPIb-IX-V and GPVI, providing a potential link between these platelet receptors and downstream TRAF4/Nox2-dependent redox pathways

    Lattice Study of Dense Matter with Two Colors and Four Flavors

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    We present results from a simulation of SU(2) lattice gauge theory with N_f=4 flavors of Wilson fermion and non-zero quark chemical potential mu, using the same 12^3x24 lattice, bare gauge coupling, and pion mass in cut-off units as a previous study with N_f=2. The string tension for N_f=4 is found to be considerably smaller implying smoother gauge field configurations. Thermodynamic observables and order parameters for superfluidity and color deconfinement are studied, and comparisons drawn between the two theories. Results for quark density and pressure as functions of mu are qualitatively similar for N_f=2 and N_f=4; in both cases there is evidence for a phase in which baryonic matter is simultaneously degenerate and confined. Results for the stress-energy tensor, however, suggest that while N_f=2 has a regime where dilute matter is non-relativistic and weakly-interacting, N_f=4 matter is relativistic and strongly-interacting for all values of mu above onset.Comment: Horizontal axes of several figures rescaled. Version accepted for publicatio
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