178 research outputs found

    Larvicidal effects of Chinaberry (Melia azederach) powder on Anopheles arabiensis in Ethiopia

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    <p>Abstract</p> <p>Background</p> <p>Synthetic insecticides are employed in the widely-used currently favored malaria control techniques involving indoor residual spraying and treated bednets. These methods have repeatedly proven to be highly effective at reducing malaria incidence and prevalence. However, rapidly emerging mosquito resistance to the chemicals and logistical problems in transporting supplies to remote locations threaten the long-term sustainability of these techniques. Chinaberry (<it>Melia azederach</it>) extracts have been shown to be effective growth-inhibiting larvicides against several insects. Because several active chemicals in the trees' seeds have insecticidal properties, the emergence of resistance is unlikely. Here, we investigate the feasibility of Chinaberry as a locally available, low-cost sustainable insecticide that can aid in controlling malaria. Chinaberry fruits were collected from Asendabo, Ethiopia. The seeds were removed from the fruits, dried and crushed into a powder. From developmental habitats in the same village, <it>Anopheles arabiensis </it>larvae were collected and placed into laboratory containers. Chinaberry seed powder was added to the larval containers at three treatment levels: 5 g m<sup>-2</sup>, 10 g m<sup>-2 </sup>and 20 g m<sup>-2</sup>, with 100 individual larvae in each treatment level and a control. The containers were monitored daily and larvae, pupae and adult mosquitoes were counted. This experimental procedure was replicated three times.</p> <p>Results</p> <p>Chinaberry seed powder caused an inhibition of emergence of 93% at the 5 g m<sup>-2 </sup>treatment level, and 100% inhibition of emergence at the two higher treatment levels. The Chinaberry had a highly statistically significant larvicidal effect at all treatment levels (χ<sup>2 </sup>= 184, 184, and 155 for 5 g m<sup>-2</sup>, 10 g m<sup>-2 </sup>and 20 g m<sup>-2</sup>, respectively; p < 0.0001 in all cases). In addition, estimates suggest that sufficient Chinaberry seed exists in Asendabo to treat developmental habitat for the duration of the rainy season and support a field trial.</p> <p>Conclusions</p> <p>Chinaberry seed is a very potent growth-inhibiting larvicide against the major African malaria vector <it>An. arabiensis</it>. The seed could provide a sustainable additional malaria vector control tool that can be used where the tree is abundant and where <it>An. arabiensis </it>is a dominant vector. Based on these results, a future village-scale field trial using the technique is warranted.</p

    Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

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    Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

    Catalogue of BRITE-Constellation targets I. Fields 1 to 14 (November 2013 - April 2016)

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    The BRIght Target Explorer (BRITE) mission collects photometric time series in two passbands aiming to investigate stellar structure and evolution. Since their launches in the years 2013 and 2014, the constellation of five BRITE nano-satellites has observed a total of more than 700 individual bright stars in 64 fields. Some targets have been observed multiple times. Thus, the total time base of the data sets acquired for those stars can be as long as nine years. Our aim is to provide a complete description of ready-to-use BRITE data, to show the scientific potential of the BRITE-Constellation data by identifying the most interesting targets, and to demonstrate and encourage how scientists can use these data in their research. We apply a decorrelation process to the automatically reduced BRITE-Constellation data to correct for instrumental effects. We perform a statistical analysis of the light curves obtained for the 300 stars observed in the first 14 fields during the first ~2.5 years of the mission. We also perform cross-identification with the International Variable Star Index. We present the data obtained by the BRITE-Constellation mission in the first 14 fields it observed from November 2013 to April 2016. We also describe the properties of the data for these fields and the 300 stars observed in them. Using these data, we detected variability in 64% of the presented sample of stars. Sixty-four stars or 21.3% of the sample have not yet been identified as variable in the literature and their data have not been analysed in detail. They can therefore provide valuable scientific material for further research. All data are made publicly available through the BRITE Public Data Archive and the Canadian Astronomy Data Centre.Comment: accepted by Astronomy & Astrophysics, 13 pages main text, 22 pages of appendi

    Deciduous Trees and the Application of Universal DNA Barcodes: A Case Study on the Circumpolar Fraxinus

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    The utility of DNA barcoding for identifying representative specimens of the circumpolar tree genus Fraxinus (56 species) was investigated. We examined the genetic variability of several loci suggested in chloroplast DNA barcode protocols such as matK, rpoB, rpoC1 and trnH-psbA in a large worldwide sample of Fraxinus species. The chloroplast intergenic spacer rpl32-trnL was further assessed in search for a potentially variable and useful locus. The results of the study suggest that the proposed cpDNA loci, alone or in combination, cannot fully discriminate among species because of the generally low rates of substitution in the chloroplast genome of Fraxinus. The intergenic spacer trnH-psbA was the best performing locus, but genetic distance-based discrimination was moderately successful and only resulted in the separation of the samples at the subgenus level. Use of the BLAST approach was better than the neighbor-joining tree reconstruction method with pairwise Kimura's two-parameter rates of substitution, but allowed for the correct identification of only less than half of the species sampled. Such rates are substantially lower than the success rate required for a standardised barcoding approach. Consequently, the current cpDNA barcodes are inadequate to fully discriminate Fraxinus species. Given that a low rate of substitution is common among the plastid genomes of trees, the use of the plant cpDNA “universal” barcode may not be suitable for the safe identification of tree species below a generic or sectional level. Supplementary barcoding loci of the nuclear genome and alternative solutions are proposed and discussed

    Global gene disruption in human cells to assign genes to phenotypes

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    Insertional mutagenesis in a haploid background can disrupt gene function[superscript 1]. We extend our earlier work by using a retroviral gene-trap vector to generate insertions in >98% of the genes expressed in a human cancer cell line that is haploid for all but one of its chromosomes. We apply phenotypic interrogation via tag sequencing (PhITSeq) to examine millions of mutant alleles through selection and parallel sequencing. Analysis of pools of cells, rather than individual clones[superscript 1] enables rapid assessment of the spectrum of genes involved in the phenotypes under study. This facilitates comparative screens as illustrated here for the family of cytolethal distending toxins (CDTs). CDTs are virulence factors secreted by a variety of pathogenic Gram-negative bacteria responsible for tissue damage at distinct anatomical sites[superscript 2]. We identify 743 mutations distributed over 12 human genes important for intoxication by four different CDTs. Although related CDTs may share host factors, they also exploit unique host factors to yield a profile characteristic for each CDT

    Measurement of differential cross sections for top quark pair production using the lepton plus jets final state in proton-proton collisions at 13 TeV

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    Phylogeography of the Patagonian otter Lontra provocax: adaptive divergence to marine habitat or signature of southern glacial refugia?

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    <p>Abstract</p> <p>Background</p> <p>A number of studies have described the extension of ice cover in western Patagonia during the Last Glacial Maximum, providing evidence of a complete cover of terrestrial habitat from 41°S to 56°S and two main refugia, one in south-eastern Tierra del Fuego and the other north of the Chiloé Island. However, recent evidence of high genetic diversity in Patagonian river species suggests the existence of aquatic refugia in this region. Here, we further test this hypothesis based on phylogeographic inferences from a semi-aquatic species that is a top predator of river and marine fauna, the huillín or Southern river otter (<it>Lontra provocax</it>).</p> <p>Results</p> <p>We examined mtDNA sequences of the control region, ND5 and Cytochrome-b (2151 bp in total) in 75 samples of <it>L. provocax </it>from 21 locations in river and marine habitats. Phylogenetic analysis illustrates two main divergent clades for <it>L. provocax </it>in continental freshwater habitat. A highly diverse clade was represented by haplotypes from the marine habitat of the Southern Fjords and Channels (SFC) region (43°38' to 53°08'S), whereas only one of these haplotypes was paraphyletic and associated with northern river haplotypes.</p> <p>Conclusions</p> <p>Our data support the hypothesis of the persistence of <it>L. provocax </it>in western Patagonia, south of the ice sheet limit, during last glacial maximum (41°S latitude). This limit also corresponds to a strong environmental change, which might have spurred <it>L. provocax </it>differentiation between the two environments.</p
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