889 research outputs found

    Interaction of Cannabis Use Disorder and Striatal Connectivity in Antipsychotic Treatment Response

    Full text link
    Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD

    An outflow in the Seyfert ESO 362-G18 revealed by Gemini-GMOS/IFU Observations

    Get PDF
    We present two-dimensional stellar and gaseous kinematics of the inner 0.7 ×\times 1.2 kpc2^{2} of the Seyfert galaxy ESO 362-G18, derived from optical spectra obtained with the GMOS/IFU on the Gemini South telescope at a spatial resolution of ≈\approx170 pc and spectral resolution of 36 km s−1^{-1}. ESO 362-G18 is a strongly perturbed galaxy of morphological type Sa or S0/a, with a minor merger approaching along the NE direction. Previous studies have shown that the [OIII] emission shows a fan-shaped extension of ≈\approx 10\arcsec\ to the SE. We detect the [OIII] doublet, [NII] and Hα{\alpha} emission lines throughout our field of view. The stellar kinematics is dominated by circular motions in the galaxy plane, with a kinematic position angle of ≈\approx137∘^{\circ}. The gas kinematics is also dominated by rotation, with kinematic position angles ranging from 122∘^{\circ} to 139∘^{\circ}. A double-Gaussian fit to the [OIII]λ\lambda5007 and Hα{\alpha} lines, which have the highest signal to noise ratios of the emission lines, reveal two kinematic components: (1) a component at lower radial velocities which we interpret as gas rotating in the galactic disk; and (2) a component with line of sight velocities 100-250 km s−1^{-1} higher than the systemic velocity, interpreted as originating in the outflowing gas within the AGN ionization cone. We estimate a mass outflow rate of 7.4 ×\times 10−2^{-2} M⊙_{\odot} yr−1^{-1} in the SE ionization cone (this rate doubles if we assume a biconical configuration), and a mass accretion rate on the supermassive black hole (SMBH) of 2.2 ×\times 10−2^{-2} M⊙_{\odot} yr−1^{-1}. The total ionized gas mass within ∼\sim84 pc of the nucleus is 3.3 ×\times 105^{5} M⊙_{\odot}; infall velocities of ∼\sim34 km s−1^{-1} in this gas would be required to feed both the outflow and SMBH accretion.Comment: 18 pages, 14 figure

    A path to real-world evidence in critical care using open-source data harmonization tools

    Get PDF
    COVID-19 highlighted the need for use of real-world data (RWD) in critical care as a near real-time resource for clinical, research, and policy efforts. Analysis of RWD is gaining momentum and can generate important evidence for policy makers and regulators. Extracting high quality RWD from electronic health records (EHRs) requires sophisticated infrastructure and dedicated resources. We sought to customize freely available public tools, supporting all phases of data harmonization, from data quality assessments to de-identification procedures, and generation of robust, data science ready RWD from EHRs. These data are made available to clinicians and researchers through CURE ID, a free platform which facilitates access to case reports of challenging clinical cases and repurposed treatments hosted by the National Center for Advancing Translational Sciences/National Institutes of Health in partnership with the Food and Drug Administration. This commentary describes the partnership, rationale, process, use case, impact in critical care, and future directions for this collaborative effort

    A Highly-Conserved Residue of the HIV-1-gp120 Inner Domain is Important for ADCC Responses Mediated by Anti-Cluster A Antibodies

    Get PDF
    Previous studies have shown that sera from HIV-1-infected individuals contain antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC). These antibodies preferentially recognize envelope glycoprotein (Env) epitopes induced upon CD4 binding. Here, we show that a highly conserved tryptophan at position 69 of the gp120 inner domain is important for ADCC mediated by anti-cluster A antibodies and sera from HIV-1-infected individuals

    Institutional maintenance work and power preservation in business exchanges: Insights from industrial supplier workshops

    Get PDF
    This paper aims to offer new theoretical and empirical insights into power dynamics in an industrial supplier workshop setting. Theoretically, it advances an institutional perspective on supplier workshops as an important venue in managing, preserving and instituting industrial market power. Based on a detailed ethnographic analysis of an industrial workshop setting, this article investigates the institutional maintenance work of Retail Co. in preserving the power dynamics of market dominance in business exchanges and market structures. Our findings revealed three previously unreported insights into the subtle, but nonetheless pervasive power from institutional maintenance work in an industrial workshop setting. First, the institutional workshop work comprised a cultural performance; constituting socialization practice through a performance game, the power of numbers in field comprehension and an award ceremony. Second, the institutional workshop work mobilized projective agency, stipulating, directing and appealing for the instituting of distinct market rules and collective identities. Finally, the institutional workshop work increases supplier docility and utility via the regulative technologies-of-the-self to enhance business planning, operations and market decision-making practice, without necessarily being seen to be disciplinarian. (C) 2015 Elsevier Inc. All rights reserved

    An outflow in the Seyfert ESO 362-G18 revealed by Gemini-GMOS/IFU observations

    Get PDF
    We present two-dimensional stellar and gaseous kinematics of the inner 0.7 × 1.2 kpc2 of the Seyfert 1.5 galaxy ESO 362-G18, derived from optical (4092–7338 Å) spectra obtained with the GMOS integral field spectrograph on the Gemini South telescope at a spatial resolution of ≈170 pc and spectral resolution of 36 km s-¹. ESO 362-G18 is a strongly perturbed galaxy of morphological type Sa or S0/a, with a minor merger approaching along the NE direction. Previous studies have shown that the [O III] emission shows a fan-shaped extension of ≈10′′ to the SE. We detect the [O III] doublet, [N II] and Hα emission lines throughout our field of view. The stellar kinematics is dominated by circular motions in the galaxy plane, with a kinematic position angle of ≈137° and is centred approximately on the continuum peak. The gas kinematics is also dominated by rotation, with kinematic position angles ranging from 122° to 139°, projected velocity amplitudes of the order of 100 km s-¹, and a mean velocity dispersion of 100 km s-¹. A double-Gaussian fit to the [O III]λ5007 and Hα lines, which have the highest signal to noise ratios of the emission lines, reveal two kinematic components: (1) a component at lower radial velocities which we interpret as gas rotating in the galactic disk; and (2) a component with line of sight velocities 100–250 km s-¹ higher than the systemic velocity, interpreted as originating in the outflowing gas within the AGN ionization cone. We estimate a mass outflow rate of 7.4 × 10-² M⊙yr-¹ in the SE ionization cone (this rate doubles if we assume a biconical configuration), and a mass accretion rate on the supermassive black hole (SMBH) of 2.2 × 10−2 M⊙ yr−1. The total ionized gas mass within ~84 pc of the nucleus is 3.3 × 105 M⊙; infall velocities of ~34 km s−1 in this gas would be required to feed both the outflow and SMBH accretion

    Why sequence all eukaryotes?

    Get PDF
    Life on Earth has evolved from initial simplicity to the astounding complexity we experience today. Bacteria and archaea have largely excelled in metabolic diversification, but eukaryotes additionally display abundant morphological innovation. How have these innovations come about and what constraints are there on the origins of novelty and the continuing maintenance of biodiversity on Earth? The history of life and the code for the working parts of cells and systems are written in the genome. The Earth BioGenome Project has proposed that the genomes of all extant, named eukaryotes-about 2 million species-should be sequenced to high quality to produce a digital library of life on Earth, beginning with strategic phylogenetic, ecological, and high-impact priorities. Here we discuss why we should sequence all eukaryotic species, not just a representative few scattered across the many branches of the tree of life. We suggest that many questions of evolutionary and ecological significance will only be addressable when whole-genome data representing divergences at all of the branchings in the tree of life or all species in natural ecosystems are available. We envisage that a genomic tree of life will foster understanding of the ongoing processes of speciation, adaptation, and organismal dependencies within entire ecosystems. These explorations will resolve long-standing problems in phylogenetics, evolution, ecology, conservation, agriculture, bioindustry, and medicine

    Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

    Get PDF
    Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components
    • …
    corecore