64 research outputs found

    Probing the Intermediate-Age Globular Clusters in NGC 5128 from Ultraviolet Observations

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    We explore the age distribution of the globular cluster (GC) system of the nearby elliptical galaxy NGC 5128 using ultraviolet (UV) photometry from Galaxy Evolution Explorer (GALEX) observations, with UV - optical colors used as the age indicator. Most GCs in NGC 5128 follow the general trends of GCs in M31 and Milky Way in UV - optical color-color diagram, which indicates that the majority of GCs in NGC 5128 are old similar to the age range of old GCs in M31 and Milky Way. A large fraction of spectroscopically identified intermediate-age GC (IAGC) candidates with ~ 3-8 Gyr are not detected in the FUV passband. Considering the nature of intermediate-age populations being faint in the far-UV (FUV) passband, we suggest that many of the spectroscopically identified IAGCs may be truly intermediate in age. This is in contrast to the case of M31 where a large fraction of spectroscopically suggested IAGCs are detected in FUV and therefore may not be genuine IAGCs but rather older GCs with developed blue horizontal branch stars. Our UV photometry strengthens the results previously suggesting the presence of GC and stellar subpopulation with intermediate age in NGC 5128. The existence of IAGCs strongly indicates the occurrence of at least one more major star formation episode after a starburst at high redshift.Comment: 8 pages, 3 figures, accepted for ApJ Lette

    How Universal Is the General Factor of Personality?

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    In various personality models, such as the Big Five, a consistent higher order general factor of personality (GFP) can be identified. One view in the literature is that the GFP reflects general social effectiveness. Most GFP studies, however, have been conducted in Western, educated, industrialized, and rich democracies (WEIRD). Therefore, to address the question of the universality of the GFP, we test whether the GFP can also be identified in a preliterate indigenous sample of Tsimane by using self-reports, spouse reports, and interviewer ratings. In the Tsimane, a viable GFP could be identified and the intercorrelations between personality traits were significantly stronger than in samples from industrial countries. The GFP correlated with the ratings of social engagement. In addition, self and spouse ratings of the GFP overlapped. Overall, the findings are in line with the notion that the GFP is a human universal and a substantive personality factor reflecting social effectiveness

    Snakebite drug discovery: high-throughput screening to identify novel snake venom metalloproteinase toxin inhibitors

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    Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left with life-long sequelae. Current antivenom therapies have several limitations including high cost, variable cross-snake species efficacy and a requirement for intravenous administration in a clinical setting. Next-generation snakebite therapies are being widely investigated with the aim to improve cost, efficacy, and safety. In recent years several small molecule drugs have shown considerable promise for snakebite indication, with oral bioavailability particularly promising for community delivery rapidly after a snakebite. However, only two such drugs have entered clinical development for snakebite. To offset the risk of attrition during clinical trials and to better explore the chemical space for small molecule venom toxin inhibitors, here we describe the first high throughput drug screen against snake venom metalloproteinases (SVMPs)—a pathogenic toxin family responsible for causing haemorrhage and coagulopathy. Following validation of a 384-well fluorescent enzymatic assay, we screened a repurposed drug library of 3,547 compounds against five geographically distinct and toxin variable snake venoms. Our drug screen resulted in the identification of 14 compounds with pan-species inhibitory activity. Following secondary potency testing, four SVMP inhibitors were identified with nanomolar EC50s comparable to the previously identified matrix metalloproteinase inhibitor marimastat and superior to the metal chelator dimercaprol, doubling the current global portfolio of SVMP inhibitors. Following analysis of their chemical structure and ADME properties, two hit-to-lead compounds were identified. These clear starting points for the initiation of medicinal chemistry campaigns provide the basis for the first ever designer snakebite specific small molecules.</jats:p

    Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death

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    Resistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukaemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR). This in turn leads to cellular accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. Our findings provide further support to the role of rewired metabolism in AML therapy resistance, unveil a connection between two apparently independent metabolic pathways and support further efforts to achieve eradication of therapy-resistant AML cells by sensitizing them to ferroptotic cell death

    Mosaic: A Satellite Constellation to Enable Groundbreaking Mars Climate System Science and Prepare for Human Exploration

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    The Martian climate system has been revealed to rival the complexity of Earth\u27s. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars\u27 diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars\u27 plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions

    The WAGGS project - I. The WiFeS Atlas of Galactic Globular cluster Spectra

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    We present the WiFeS Atlas of Galactic Globular cluster Spectra, a library of integrated spectra of Milky Way and Local Group globular clusters. We used the WiFeS integral field spectrograph on the Australian National University 2.3 m telescope to observe the central regions of 64 Milky Way globular clusters and 22 globular clusters hosted by the Milky Way’s low-mass satellite galaxies. The spectra have wider wavelength coverage (3300–9050 Å) and higher spectral resolution (R = 6800) than existing spectral libraries of Milky Way globular clusters. By including Large and Small Magellanic Cloud star clusters, we extend the coverage of parameter space of existing libraries towards young and intermediate ages. While testing stellar population synthesis models and analysis techniques is the main aim of this library, the observations may also further our understanding of the stellar populations of Local Group globular clusters and make possible the direct comparison of extragalactic globular cluster integrated light observations with well-understood globular clusters in the Milky Way. The integrated spectra are publicly available via the project website

    Effects of transportation, transport medium and re-housing on Xenopus laevis (Daudin)

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    Understanding the immediate and longer-term effects of transportation and re-housing in a laboratory species is crucial in order to refine the transfer process, enable the optimal introduction of new animals to a novel environment and to provide a sufficient acclimatisation period before usage. Whilst consideration of animal welfare in most model vertebrate species has received attention, little quantitative evidence exists for the optimal care of the common laboratory amphibian Xenopus laevis. Techniques for the non-invasive welfare assessment of amphibians are also limited and here a non-invasive physiological assay was developed to investigate the impacts of transportation, transport medium and re-housing on X. laevis. First the impacts of transportation and transport medium (water, damp sponge or damp sphagnum moss) were investigated. Transportation caused an increase in waterborne corticosterone regardless of transport medium. Frogs transported in damp sphagnum moss also had a greater decrease in body mass in comparison to frogs not transported, suggesting that this is the least suitable transport medium for X. laevis. Next the prolonged impacts of transportation and re-housing were investigated. Frogs were transported between research facilities with different housing protocols. Samples were collected prior to and immediately following transportation, as well as 1 day, 7 days and 35 days after re-housing. Water-borne corticosterone increased following transportation and remained high for at least 7 days, decreasing to baseline levels by 35 days. Body mass decreased following transportation and remained lower than baseline levels across the entire 35 day observation period. These findings suggest the process of transportation and re-housing is stressful in this species. Together these findings have important relevance for both improving animal welfare and ensuring optimal and efficient scientific research

    Functional materials discovery using energy–structure–function maps

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    Molecular crystals cannot be designed in the same manner as macroscopic objects, because they do not assemble according to simple, intuitive rules. Their structures result from the balance of many weak interactions, rather than from the strong and predictable bonding patterns found in metal–organic frameworks and covalent organic frameworks. Hence, design strategies that assume a topology or other structural blueprint will often fail. Here we combine computational crystal structure prediction and property prediction to build energy–structure–function maps that describe the possible structures and properties that are available to a candidate molecule. Using these maps, we identify a highly porous solid, which has the lowest density reported for a molecular crystal so far. Both the structure of the crystal and its physical properties, such as methane storage capacity and guest-molecule selectivity, are predicted using the molecular structure as the only input. More generally, energy–structure–function maps could be used to guide the experimental discovery of materials with any target function that can be calculated from predicted crystal structures, such as electronic structure or mechanical properties
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