853 research outputs found

    PARSES: A Pipeline for Analysis of RNA-Sequencing Exogenous Sequences

    Get PDF
    RNA-Sequencing (RNA-Seq) has become one of the most widely used techniques to interrogate the transcriptome of an organism since the advent of next generation sequencing technologies [1]. A plethora of tools have been developed to analyze and visualize the transcriptome data from RNA-Seq experiments, solving the problem of mapping reads back to the host organism\u27s genome [2] [3]. This allows for analysis of most reads produced by the experiments, but these tools typically discard reads that do not match well with the reference genome. This additional information could reveal important insight into the experiment and possible contributing factors to the condition under consideration. We introduce PARSES, a pipeline constructed from existing sequence analysis tools, which allows the user to interrogate RNA-Sequencing experiments for possible biological contamination or the presence of exogenous sequences that may shed light on other factors influencing an organism\u27s condition

    PARSES: A Pipeline for Analysis of RNA-Sequencing Exogenous Sequences

    Get PDF
    RNA-Sequencing (RNA-Seq) has become one of the most widely used techniques to interrogate the transcriptome of an organism since the advent of next generation sequencing technologies [1]. A plethora of tools have been developed to analyze and visualize the transcriptome data from RNA-Seq experiments, solving the problem of mapping reads back to the host organism\u27s genome [2] [3]. This allows for analysis of most reads produced by the experiments, but these tools typically discard reads that do not match well with the reference genome. This additional information could reveal important insight into the experiment and possible contributing factors to the condition under consideration. We introduce PARSES, a pipeline constructed from existing sequence analysis tools, which allows the user to interrogate RNA-Sequencing experiments for possible biological contamination or the presence of exogenous sequences that may shed light on other factors influencing an organism\u27s condition

    MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis

    Get PDF
    Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell–dependent and depression of Th1 cell–dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain–containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b+ expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization

    Lactic Acid Induces Aberrant Amyloid Precursor Protein Processing by Promoting Its Interaction with Endoplasmic Reticulum Chaperone Proteins

    Get PDF
    Lactic acid, a natural by-product of glycolysis, is produced at excess levels in response to impaired mitochondrial function, high-energy demand, and low oxygen availability. The enzyme involved in the production of β-amyloid peptide (Aβ) of Alzheimer's disease, BACE1, functions optimally at lower pH, which led us to investigate a potential role of lactic acid in the processing of amyloid precursor protein (APP).Lactic acid increased levels of Aβ40 and 42, as measured by ELISA, in culture medium of human neuroblastoma cells (SH-SY5Y), whereas it decreased APP metabolites, such as sAPPα. In cell lysates, APP levels were increased and APP was found to interact with ER-chaperones in a perinuclear region, as determined by co-immunoprecipitation and fluorescence microscopy studies. Lactic acid had only a very modest effect on cellular pH, did increase the levels of ER chaperones Grp78 and Grp94 and led to APP aggregate formation reminiscent of aggresomes.These findings suggest that sustained elevations in lactic acid levels could be a risk factor in amyloidogenesis related to Alzheimer's disease through enhanced APP interaction with ER chaperone proteins and aberrant APP processing leading to increased generation of amyloid peptides and APP aggregates

    Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

    Get PDF
    The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of ttt\overline{t}, W+bbW+b\overline{b} and W+ccW+c\overline{c} is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 ±\pm 0.02 \mbox{fb}^{-1}. The WW bosons are reconstructed in the decays WνW\rightarrow\ell\nu, where \ell denotes muon or electron, while the bb and cc quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

    The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

    Get PDF
    Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients
    corecore