378 research outputs found

    Astrometric Discovery of GJ 164B

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    We discovered a low-mass companion to the M-dwarf GJ 164 with the CCD-based imaging system of the Stellar Planet Survey (STEPS) astrometric program. The existence of GJ 164B was confirmed with Hubble Space Telescope NICMOS imaging observations. A high-dispersion spectral observation in V sets a lower limit of delta m> 2.2 mag between the two components of the system. Based upon our parallax value of 0.082 +/- 0.008, we derive the following orbital parameters: P = 2.04 +/- 0.03 y, a = 1.03 +/- 0.03 AU, and Mtotal = 0.265 +/- 0.020 MSun. The component masses are MA = 0.170 +/- 0.015 MSun and MB = 0.095 +/- 0.015 MSun. Based on its mass, colors, and spectral properties, GJ 164B has spectral type M6-8 V.Comment: pdf file 14 pages with 6 fig

    Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes

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    <p>Abstract</p> <p>Background</p> <p>New drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes, <it>Caenorhabditis elegans, Drosophila melanogaster, Mus musculus </it>and <it>Saccharomyces cerevisiae</it>, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset.</p> <p>Results</p> <p>Cross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets from <it>Ancylostoma caninum </it>and <it>Haemonchus contortus </it>- two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools.</p> <p>Conclusions</p> <p>The present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.</p

    Temperature and precipitation at migratory grounds influence demographic trends of an Arctic‐breeding bird

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    Anthropogenic climate disruption, including temperature and precipitation regime shifts, has been linked to animal population declines since the mid‐20th century. However, some species, such as Arctic‐breeding geese, have thrived during this period. An increased understanding of how climate disruption might link to demographic rates in thriving species is an important perspective in quantifying the impact of anthropogenic climate disruption on the global state of nature. The Greenland barnacle goose (Branta leucopsis) population has increased tenfold in abundance since the mid‐20th century. A concurrent weather regime shift towards warmer, wetter conditions occurred throughout its range in Greenland (breeding), Ireland and Scotland (wintering) and Iceland (spring and autumn staging). The aim of this study was to determine the relationship between weather and demographic rates of Greenland barnacle geese to discern the role of climate shifts in the population trend. We quantified the relationship between temperature and precipitation and Greenland barnacle goose survival and productivity over a 50 year period from 1968 to 2018. We detected significant positive relationships between warmer, wetter conditions on the Icelandic spring staging grounds and survival. We also detected contrasting relationships between warmer, wetter conditions during autumn staging and survival and productivity, with warm, dry conditions being the most favourable for productivity. Survival increased in the latter part of the study period, supporting the possibility that spring weather regime shifts contributed to the increasing population trend. This may be related to improved forage resources, as warming air temperatures have been shown to improve survival rates in several other Arctic and northern terrestrial herbivorous species through indirect bottom‐up effects on forage availability

    Identification of Bruton's tyrosine kinase as a therapeutic target in acute myeloid leukemia

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    Bruton's tyrosine kinase (BTK) is a cytoplasmic protein found in all hematopoietic cell lineages except for T cells. BTK mediates signalling downstream of a number of receptors. Pharmacological targeting of BTK using ibrutinib (previously PCI-32765) has recently shown encouraging clinical activity in a range of lymphoid malignancies. This study reports for the first time that ibrutinib inhibits blast proliferation from human acute myeloid leukaemia (AML) and that treatment with ibrutinib significantly augmented cytotoxic activities of standard AML chemotherapy cytarabine or daunorubicin. Here we describe that BTK is constitutively phosphorylated in the majority of AML samples tested, with BTK phosphorylation correlating highly with the cell's cytotoxic sensitivity towards ibrutinib. BTK targeted RNAi knock-down reduced colony forming capacity of primary AML blasts and proliferation of AML cell lines. We showed ibrutinib binds at nanomolar range to BTK. Furthermore, we also showed ibrutinib's anti-proliferative effects in AML are mediated via an inhibitory effect on downstream nuclear factor-ÎșB (NF-ÎșB) survival pathways. Moreover, ibrutinib inhibited AML cell adhesion to bone marrow stroma. Furthermore, these effects of ibrutinib in AML were seen at comparable concentrations efficacious in chronic lymphocytic leukemia (CLL). These results provide a biologic rationale for clinical evaluation of BTK inhibition in AML patients

    Stratospheric Gravity Wave Fluxes and Scales during DEEPWAVE

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    During the Deep Propagating Gravity Wave Experiment (DEEPWAVE) project in June and July 2014, the Gulfstream V research aircraft flew 97 legs over the Southern Alps of New Zealand and 150 legs over the Tasman Sea and Southern Ocean, mostly in the low stratosphere at 12.1-km altitude. Improved instrument calibration, redundant sensors, longer flight legs, energy flux estimation, and scale analysis revealed several new gravity wave properties. Over the sea, flight-level wave fluxes mostly fell below the detection threshold. Over terrain, disturbances had characteristic mountain wave attributes of positive vertical energy flux (EFz), negative zonal momentum flux, and upwind horizontal energy flux. In some cases, the fluxes changed rapidly within an 8-h flight, even though environmental conditions were nearly unchanged. The largest observed zonal momentum and vertical energy fluxes were MFx = −550 mPa and EFz = 22 W m−2, respectively. A wide variety of disturbance scales were found at flight level over New Zealand. The vertical wind variance at flight level was dominated by short “fluxless” waves with wavelengths in the 6–15-km range. Even shorter scales, down to 500 m, were found in wave breaking regions. The wavelength of the flux-carrying mountain waves was much longer—mostly between 60 and 150 km. In the strong cases, however, with EFz \u3e 4 W m−2, the dominant flux wavelength decreased (i.e., “downshifted”) to an intermediate wavelength between 20 and 60 km. A potential explanation for the rapid flux changes and the scale “downshifting” is that low-level flow can shift between “terrain following” and “envelope following” associated with trapped air in steep New Zealand valleys

    Selectivity of Rh⋅⋅⋅H−C Binding in a σ-Alkane Complex Controlled by the Secondary Microenvironment in the Solid State

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    By using single-crystal to single-crystal solid-state molecular organometallic (SMOM) techniques, the σ -alkane complex [Rh( t Bu 2 PCH 2 CH 2 CH 2 P t Bu 2 )( η 2 , η 2 -C 7 H 12 )][BAr F 4 ] (Ar F = 3,5-(CF 3 ) 2 C 6 H 3 ) is synthesized and structurally characterized, in which the alkane (norbornane) binds through two exo -C-H···Rh interactions. In contrast, the bis-cyclohexyl phosphine analogue shows endo -alkane binding. Comparison of the two systems, supported by periodic DFT calculations, NCI plots and Hirshfeld surface analyses, trace this different regioselectivity to subtle changes in the local microenvironment surrounding the alkane ligand. A tertiary periodic structure supporting a secondary microenvironment that controls binding at the metal site has parallels with enzymes. The new σ -alkane complex is also a catalyst for solid/gas 1-butene isomerization, and catalyst resting states are identified for this

    Genomic characterisation of EΌ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

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    The EΌ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising EΌ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of EΌ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.We acknowledge the following funding agencies: Leukaemia Foundation of Australia, Arrow Bone Marrow Transplant Foundation, National Health and Medical Research Council Australia, Cancer Council Victoria, Victorian Cancer Agency, Australian Cancer Research Foundation, Peter MacCallum Cancer Centre Foundation, National Institutes of Health
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