2,499 research outputs found

    Functional Literacy, Educational Attainment and Earnings - A Multi-Country Comparison

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    In this paper a rich and innovative dataset, the International Adult Literacy Survey, is used to examine the impact of functional literacy on earnings. We show that the estimated return to formal education is sensitive to the inclusion of literacy - excluding it biases the return to education in many countries by significant amounts. Literacy itself has a well-determined effect on earnings in all countries though with considerable variation in the size of the effect. The benefits of literacy do not only arise from increasing low levels of literacy: increases at already high levels generate substantial increases in earnings in some countries. In general we find little interaction between schooling and literacy though for a few countries they appear to complement each other.

    Aryl Phosphoramidates of 5-Phospho Erythronohydroxamic Acid, A New Class of Potent Trypanocidal Compounds

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    RNAi and enzymatic studies have shown the importance of 6-phosphogluconate dehydrogenase (6-PGDH) in Trypanosoma brucei for the parasite survival and make it an attractive drug target for the development of new treatments against human African trypanosomiasis. 2,3-O-Isopropylidene-4-erythrono hydroxamate is a potent inhibitor of parasite Trypanosoma brucei 6-phosphogluconate dehydrogenase (6-PGDH), the third enzyme of the pentose phosphate pathway. However, this compound does not have trypanocidal activity due to its poor membrane permeability. Consequently, we have previously reported a prodrug approach to improve the antiparasitic activity of this inhibitor by converting the phosphate group into a less charged phosphate prodrug. The activity of prodrugs appeared to be dependent on their stability in phosphate buffer. Here we have successfully further extended the development of the aryl phosphoramidate prodrugs of 2,3-O-isopropylidene-4-erythrono hydroxamate by synthesizing a small library of phosphoramidates and evaluating their biological activity and stability in a variety of assays. Some of the compounds showed high trypanocidal activity and good correlation of activity with their stability in fresh mouse blood

    Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli

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    Priming and activating immune stimuli have profound effects on macrophages, however, studies generally evaluate stimuli in isolation rather than in combination. In this study we have investigated the effects of pro-inflammatory and anti-inflammatory stimuli either alone or in combination on macrophage metabolism. These stimuli include host factors such as IFNγ and ovalbumin-immunoglobulin immune complexes, or pathogen factors such as LPS. Untargeted LC-MS based metabolomics provided an in-depth profile of the macrophage metabolome, and revealed specific changes in metabolite abundance upon either individual stimuli or combined stimuli. Here, by factoring in an interaction term in the linear model, we define the metabolome interactome. This approach allowed us to determine whether stimuli interact in a synergistic or antagonistic manner. In conclusion this study demonstrates a robust approach to interrogate immune-metabolism, especially systems that model host-pathogen interactions

    Population Structure in The Brown Tube Sponge (agelas Conifera) in The Florida Reef Tract And Caribbean

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    Sponges are broadly distributed, occur in a wide range of habitats, and comprise a substantial amount of the biomass and macro-biodiversity on coral reefs. Despite their ubiquity in reef ecosystems, their dispersal dynamics are largely unknown. Here we report on gene flow and population structure for the common brown tube sponge, Agelas conifera (Demospongiae, Poecilosclerida) in the Florida reef tract and Caribbean. Over 300 samples collected from ten geographically distinct locations throughout Florida and the Caribbean are being analyzed for variation at eight microsatellite loci. Preliminary results from screening four loci in 295 individuals from eight locations indicated significant population structure overall (FST = 0.072; P = 0.0018) with a significant heterozygosity deficit (FIS = 0.310; P = 0.001). Lower FST values occurred within the Florida reef tract sites compared to those between Caribbean island locations suggesting relatively greater gene flow within the Florida reef system. Significant isolation by distance was not found to occur Caribbean-wide (r = 0.25; P = 0.14), nor within the Florida reef tract (r = 0.39; P = 0.10). Fine scale population structure occurred among sites separated by \u3c1 km around the islands of Utila (Honduras) and St. Croix (USVI) suggesting A. conifera recruitment in these areas is highly local source dependant. In contrast, no structure was observed among sites around Grand Cayman (Cayman Islands). Only populations within St. Croix showed a significant isolation by distance pattern (r = 0.74; P \u3c 0.001). The strong overall and in some instances even highly localized genetic structure observed is consistent with the typically short larval durations known for sponges generally; suggesting recruitment in these important reef biomass components may be driven mainly from local sources

    A library of infectious hepatitis C viruses with engineered mutations in the E2 gene reveals growth-adaptive mutations that modulate interactions with scavenger receptor class B type I

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    While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. IMPORTANCE Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability

    Simplified three-dimensional tissue clearing and incorporation of colorimetric phenotyping.

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    Tissue clearing methods promise to provide exquisite three-dimensional imaging information; however, there is a need for simplified methods for lower resource settings and for non-fluorescence based phenotyping to enable light microscopic imaging modalities. Here we describe the simplified CLARITY method (SCM) for tissue clearing that preserves epitopes of interest. We imaged the resulting tissues using light sheet microscopy to generate rapid 3D reconstructions of entire tissues and organs. In addition, to enable clearing and 3D tissue imaging with light microscopy methods, we developed a colorimetric, non-fluorescent method for specifically labeling cleared tissues based on horseradish peroxidase conversion of diaminobenzidine to a colored insoluble product. The methods we describe here are portable and can be accomplished at low cost, and can allow light microscopic imaging of cleared tissues, thus enabling tissue clearing and imaging in a wide variety of settings

    Waveguiding and nonlinear optical properties of three-dimensional waveguides in LiTaO<inf>3</inf> written by high-repetition rate ultrafast laser

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    We report the fabrication of waveguides in lithium tantalate using a 250 kHz high-repetition rate ultrafast laser at 771 nm and the characterization of the resulting laser induced structure with second harmonic microscopy. Waveguides operating at the 1.5 μm telecommunication wavelength were formed above and below the focal volume using pulse energies ranging from 100 to 1.6 J and translation speeds from 100 μms to 5 mms. The second harmonic microscopy reveals no degradation of the electro-optic coefficient in the guiding region above the focal volume. © 2008 American Institute of Physics

    Contrasting Patterns of Population Structure and Dispersal for the Giant Barrel Sponge (Xestospongia muta) within the Florida Reef Tract and Caribbean

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    Sponges are one of the dominant fauna on Florida and Caribbean reefs, with species diversity often exceeding that of scleractinian corals. Despite their importance as structural components and habitat providers on reefs, their dispersal dynamics are little understood. We utilized eight microsatellite markers to study the population structure and migration patterns of the giant barrel sponge (Xestospongia muta), a widespread species throughout Florida and the Caribbean. Bayesian multilocus genotype analyses clustered 157 samples from the Bahamas, Honduras, and the US Virgin Islands into three distinct groups. 159 samples from nine locations within 284 km of the Florida reef tract (Key Largo to the Dry Tortugas) formed a fourth group. Population structure among the four groups was high (FST = 0.155; P = 0.001), with no recent migration among the groups. In contrast, high levels of migration were detected within the Florida reef tract. Reefs in the Upper Keys (Long Key) appear to be sources of larvae to reefs in the north (Key Largo) and also to reefs in the south (Key West and the Dry Tortugas). This pattern of migration closely matches current pathways within the South Florida recirculation system, suggesting that currents play an important role in dispersing X. muta larvae within the Florida reef tract. Although there was an overall lack of isolation by distance among the four groups, a significant correlation between genetic and geographic distance was found among the Florida sampling sites indicating that mating within the reef tract is not random. Asexual reproduction appears not to be the cause as only 1.3% of individuals in Florida shared the same genotype (1.6% overall). Rather, limited larval dispersal along the reef tract and among Caribbean locations has probably led to inbreeding within reefs, explaining the significant deficit in heterozygosity detected (FIS = 0.219; P = 0.001)
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