71 research outputs found

    Baddeleyite Microstructures in Variably Shocked Martian Meteorites: An Opportunity to Link Shock Barometry and Robust Geochronology

    Get PDF
    eid: 2302 adsurl: https://ui.adsabs.harvard.edu/abs/2020LPI....51.2302S adsnote: Provided by the SAO/NASA Astrophysics Data Syste

    Dating martian mafic crust; microstructurally constrained baddeleyite geochronology of enriched shergottites Northwest Africa (NWA) 7257, NWA 8679 and Zagami

    Get PDF
    This work was supported by Science and Technology Facilities Council grant [ST/S000291/1] to JRD.Baddeleyite (monoclinic; m-ZrO2) is a widespread accessory phase within shergottites. However, the effects of shock loading on baddeleyite U-Pb isotopic systematics, and therefore its reliability as a geochronometer within highly shocked lithologies, are less well constrained. To investigate the effects of shock metamorphism on baddeleyite U-Pb chronology, we have conducted high-resolution microstructural analysis and in-situ U-Pb isotopic measurements for baddeleyite within enriched basaltic shergottites Northwest Africa (NWA) 7257, NWA 8679 and Zagami. Electron backscatter diffraction (EBSD) analyses of baddeleyite reveal significant microstructural heterogeneity within individual thin sections, recording widespread partial to complete reversion from high-pressure (≥3.3 GPa) orthorhombic zirconia polymorphs. We define a continuum of baddeleyite microstructures into four groupings on the basis of microstructural characteristics, including rare grains that retain magmatic twin relationships. Uncorrected U-Pb isotopic measurements form Tera-Wasserburg discordia, yielding new 238U-206Pb discordia ages of 195 ± 15 Ma (n = 17) for NWA 7257 and 220 ± 23 Ma (n = 10) for NWA 8679. Critically, there is no resolvable link between baddeleyite microstructure and U-Pb isotope systematics, indicating negligible open-system behaviour of U-Pb during zirconia phase transformations. Instead, we confirm that high post-shock temperatures exert the greatest control on Pb mobility within shocked baddeleyite; in the absence of high post-shock temperatures, baddeleyite yield robust U-Pb isotope systematics and date the age of magmatic crystallization. Low bulk post-shock temperatures recorded within Zagami (≤220 °C), and suggested within NWA 7257 and NWA 8679 by baddeleyite microstructure and other petrological constraints, confirm that the previously derived baddeleyite age of Zagami records magmatic crystallization, and provide greater age diversity to 225 Ma to 160 Ma enriched shergottites. While our data yield no resolvable link between microstructure and U-Pb isotopic composition, we strongly recommend that microstructural analyses should represent an essential step of baddeleyite U-Pb chronology within planetary (e.g., martian, lunar, asteroidal) and shocked terrestrial samples, allowing full contextualisation prior to destructive isotopic techniques. Microstructurally constrained in-situ U-Pb analyses of baddeleyite thus define new opportunities for the absolute chronology of martian meteorites and, more broadly, shocked planetary materials.Publisher PDFPeer reviewe

    Transformation-induced changes in the DNA-nuclear matrix interface, revealed by high-throughput analysis of DNA halos

    Get PDF
    In higher eukaryotic nuclei, DNA is periodically anchored to an extraction-resistant protein structure, via matrix attachment regions. We describe a refined and accessible method to non-subjectively, rapidly and reproducibly measure both size and stability of the intervening chromatin loops, and use it to demonstrate that malignant transformation compromises the DNA-nuclear matrix interface

    HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase

    Get PDF
    The Trans-activator protein (Tat) of human immunodeficiency virus (HIV) is a pleiotropic protein involved in different aspects of AIDS pathogenesis. As a number of viral proteins Tat is suspected to disturb mitochondrial function. We prepared pure synthetic full-length Tat by native chemical ligation (NCL), and Tat peptides, to evaluate their direct effects on isolated mitochondria. Submicromolar doses of synthetic Tat cause a rapid dissipation of the mitochondrial transmembrane potential (ΔΨm) as well as cytochrome c release in mitochondria isolated from mouse liver, heart, and brain. Accordingly, Tat decreases substrate oxidation by mitochondria isolated from these tissues, with oxygen uptake being initially restored by adding cytochrome c. The anion-channel inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) protects isolated mitochondria against Tat-induced mitochondrial membrane permeabilization (MMP), whereas ruthenium red, a ryanodine receptor blocker, does not. Pharmacologic inhibitors of the permeability transition pore, Bax/Bak inhibitors, and recombinant Bcl-2 and Bcl-XL proteins do not reduce Tat-induced MMP. We finally observed that Tat inhibits cytochrome c oxidase (COX) activity in disrupted mitochondria isolated from liver, heart, and brain of both mouse and human samples, making it the first described viral protein to be a potential COX inhibitor

    Asenapine effects in animal models of psychosis and cognitive function

    Get PDF
    Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, α-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties. The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone. Amphetamine-stimulated locomotor activity (Amp-LMA; 1.0 or 3.0 mg/kg s.c.) and apomorphine-disrupted prepulse inhibition (Apo-PPI; 0.5 mg/kg s.c.) were used as tests for antipsychotic activity. Delayed non-match to place (DNMTP) and five-choice serial reaction (5-CSR) tasks were used to assess short-term spatial memory and attention, respectively. Asenapine doses varied across tasks: Amp-LMA (0.01–0.3 mg/kg s.c.), Apo-PPI (0.001–0.3 mg/kg s.c.), DNMTP (0.01–0.1 mg/kg s.c.), and 5-CSR (0.003–0.3 mg/kg s.c.). Asenapine was highly potent (active at 0.03 mg/kg) in the Amp-LMA and Apo-PPI assays. DNMTP or 5-CSR performance was not improved by asenapine, olanzapine, or risperidone. All agents (P < 0.01) reduced DNMTP accuracy at short delays; post hoc analyses revealed that only 0.1 mg/kg asenapine and 0.3 mg/kg risperidone differed from vehicle. All active agents (asenapine, 0.3 mg/kg; olanzapine, 0.03–0.3 mg/kg; and risperidone, 0.01–0.1 mg/kg) significantly impaired 5-CSR accuracy (P < 0.05). Asenapine has potent antidopaminergic properties that are predictive of antipsychotic efficacy. Asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Rather, at doses greater than those required for antipsychotic activity, asenapine impaired cognitive performance due to disturbance of motor function, an effect also observed with olanzapine and risperidone

    Transmission of H7N9 influenza virus in mice by different infective routes

    Get PDF
    BACKGROUND: On 19 February 2013, the first patient infected with a novel influenza A H7N9 virus from an avian source showed symptoms of sickness. More than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland China since then. Laboratory-confirmed, human-to-human H7N9 virus transmission has not been documented between individuals having close contact; however, this transmission route could not be excluded for three families. To control the spread of the avian influenza H7N9 virus, we must better understand its pathogenesis, transmissibility, and transmission routes in mammals. Studies have shown that this particular virus is transmitted by aerosols among ferrets. METHODS: To study potential transmission routes in animals with direct or close contact to other animals, we investigated these factors in a murine model. RESULTS: Viable H7N9 avian influenza virus was detected in the upper and lower respiratory tracts, intestine, and brain of model mice. The virus was transmissible between mice in close contact, with a higher concentration of virus found in pharyngeal and ocular secretions, and feces. All these biological materials were contagious for naïve mice. CONCLUSIONS: Our results suggest that the possible transmission routes for the H7N9 influenza virus were through mucosal secretions and feces. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-422X-11-185) contains supplementary material, which is available to authorized users

    IL-1α Signaling Is Critical for Leukocyte Recruitment after Pulmonary Aspergillus fumigatus Challenge

    Get PDF
    Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how A. fumigatus growth is controlled in the respiratory tract is developing, but still limited. Alveolar macrophages, lung resident macrophages, and airway epithelial cells constitute the first lines of defense against inhaled A. fumigatus conidia. Subsequently, neutrophils and inflammatory CCR2+ monocytes are recruited to the respiratory tract to prevent fungal growth. However, the mechanism of neutrophil and macrophage recruitment to the respiratory tract after A. fumigatus exposure remains an area of ongoing investigation. Here we show that A. fumigatus pulmonary challenge induces expression of the inflammasome-dependent cytokines IL-1β and IL-18 within the first 12 hours, while IL-1α expression continually increases over at least the first 48 hours. Strikingly, Il1r1-deficient mice are highly susceptible to pulmonary A. fumigatus challenge exemplified by robust fungal proliferation in the lung parenchyma. Enhanced susceptibility of Il1r1-deficient mice correlated with defects in leukocyte recruitment and anti-fungal activity. Importantly, IL-1α rather than IL-1β was crucial for optimal leukocyte recruitment. IL-1α signaling enhanced the production of CXCL1. Moreover, CCR2+ monocytes are required for optimal early IL-1α and CXCL1 expression in the lungs, as selective depletion of these cells resulted in their diminished expression, which in turn regulated the early accumulation of neutrophils in the lung after A. fumigatus challenge. Enhancement of pulmonary neutrophil recruitment and anti-fungal activity by CXCL1 treatment could limit fungal growth in the absence of IL-1α signaling. In contrast to the role of IL-1α in neutrophil recruitment, the inflammasome and IL-1β were only essential for optimal activation of anti-fungal activity of macrophages. As such, Pycard-deficient mice are mildly susceptible to A. fumigatus infection. Taken together, our data reveal central, non-redundant roles for IL-1α and IL-1β in controlling A. fumigatus infection in the murine lung

    Urban Biodiversity and Landscape Ecology: Patterns, Processes and Planning

    Get PDF
    Effective planning for biodiversity in cities and towns is increasingly important as urban areas and their human populations grow, both to achieve conservation goals and because ecological communities support services on which humans depend. Landscape ecology provides important frameworks for understanding and conserving urban biodiversity both within cities and considering whole cities in their regional context, and has played an important role in the development of a substantial and expanding body of knowledge about urban landscapes and communities. Characteristics of the whole city including size, overall amount of green space, age and regional context are important considerations for understanding and planning for biotic assemblages at the scale of entire cities, but have received relatively little research attention. Studies of biodiversity within cities are more abundant and show that longstanding principles regarding how patch size, configuration and composition influence biodiversity apply to urban areas as they do in other habitats. However, the fine spatial scales at which urban areas are fragmented and the altered temporal dynamics compared to non-urban areas indicate a need to apply hierarchical multi-scalar landscape ecology models to urban environments. Transferring results from landscape-scale urban biodiversity research into planning remains challenging, not least because of the requirements for urban green space to provide multiple functions. An increasing array of tools is available to meet this challenge and increasingly requires ecologists to work with planners to address biodiversity challenges. Biodiversity conservation and enhancement is just one strand in urban planning, but is increasingly important in a rapidly urbanising world

    Multi-messenger observations of a binary neutron star merger

    Get PDF
    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
    corecore