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  • 1
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    A Toxoplasma Target for Acyl-protein Thioesterase Inhibitors [Membrane Biology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-09-21
    Description: In eukaryotic organisms, cysteine palmitoylation is an important reversible modification that impacts protein targeting, folding, stability, and interactions with partners. Evidence suggests that protein palmitoylation contributes to key biological processes in Apicomplexa with the recent palmitome of the malaria parasite Plasmodium falciparum reporting over 400 substrates that are modified with palmitate by a broad range of protein S-acyl transferases. Dynamic palmitoylation cycles require the action of an acyl-protein thioesterase (APT) that cleaves palmitate from substrates and conveys reversibility to this posttranslational modification. In this work, we identified candidates for APT activity in Toxoplasma gondii. Treatment of parasites with low micromolar concentrations of β-lactone- or triazole urea-based inhibitors that target human APT1 showed varied detrimental effects at multiple steps of the parasite lytic cycle. The use of an activity-based probe in combination with these inhibitors revealed the existence of several serine hydrolases that are targeted by APT1 inhibitors. The active serine hydrolase, TgASH1, identified as the homologue closest to human APT1 and APT2, was characterized further. Biochemical analysis of TgASH1 indicated that this enzyme cleaves substrates with a specificity similar to APTs, and homology modeling points toward an APT-like enzyme. TgASH1 is dispensable for parasite survival, which indicates that the severe effects observed with the β-lactone inhibitors are caused by the inhibition of non-TgASH1 targets. Other ASH candidates for APT activity were functionally characterized, and one of them was found to be resistant to gene disruption due to the potential essential nature of the protein.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 2
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    Design of a 400 kV deep underground, high detector efficiency, high target density, high beam intensity accelerator facility (2011)
    American Physical Society (APS)
    Details
    Publication Date: 2011-10-05
    Description: Author(s): A. Lemut, M. Couder, D. Winklehner, U. Greife, A. Hodgkinson, D. Leitner, M. Leitner, J. S. Saba, P. A. Vetter, W. L. Waldron, and M. Wiescher [Phys. Rev. ST Accel. Beams 14, 100101] Published Tue Oct 04, 2011
    Keywords: Low- and Intermediate-Energy Accelerators
    Electronic ISSN: 1098-4402
    Topics: Physics
    Published by American Physical Society (APS)
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  • 3
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    Band structure of ^{235}U (2012)
    American Physical Society (APS)
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    Publication Date: 2012-12-22
    Description: Author(s): D. Ward, A. O. Macchiavelli, R. M. Clark, D. Cline, M. Cromaz, M. A. Deleplanque, R. M. Diamond, P. Fallon, A. Görgen, A. B. Hayes, G. J. Lane, I.-Y. Lee, T. Nakatsukasa, G. Schmidt, F. S. Stephens, C. E. Svensson, R. Teng, K. Vetter, and C. Y. Wu Over a period of several years we have performed three separate experiments at Lawrence Berkeley National Laboratory's 88-Inch Cyclotron in which 235 U (thick target) was Coulomb-excited. The program involved stand-alone experiments with Gammmasphere and with the 8pi Spectrometer using 136 Xe beams at... [Phys. Rev. C 86, 064319] Published Fri Dec 21, 2012
    Keywords: Nuclear Structure
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
    Published by American Physical Society (APS)
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  • 4
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    IJERPH, Vol. 11, Pages 7896-7917: The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies (2014)
    MDPI Publishing
    Details
    Publication Date: 2014-08-07
    Description: The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO) in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS), using the Inverse Distance Weighted (IDW) interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura), the presence of another vector (Anopheles labranchiae) besides A. atroparvus (Levante) or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia). In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.
    Print ISSN: 1661-7827
    Electronic ISSN: 1660-4601
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by MDPI Publishing
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  • 5
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    Generalized Radially Self-Accelerating Helicon Beams (2014)
    American Physical Society (APS)
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    Publication Date: 2014-10-29
    Description: Author(s): Christian Vetter, Toni Eichelkraut, Marco Ornigotti, and Alexander Szameit We report, in theory and experiment, on a new class of optical beams that are radially self-accelerating and nondiffracting. These beams continuously evolve on spiraling trajectories while maintaining their amplitude and phase distribution in their rotating rest frame. We provide a detailed insight ... [Phys. Rev. Lett. 113, 183901] Published Tue Oct 28, 2014
    Keywords: Nonlinear Dynamics, Fluid Dynamics, Classical Optics, etc.
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 6
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    Remote Sensing, Vol. 6, Pages 1739-1759: GIS-Based Roughness Derivation for Flood Simulations: A Comparison of Orthophotos, LiDAR and Crowdsourced Geodata (2014)
    MDPI Publishing
    Details
    Publication Date: 2014-02-25
    Description: Natural disasters like floods are a worldwide phenomenon and a serious threat to mankind. Flood simulations are applications of disaster control, which are used for the development of appropriate flood protection. Adequate simulations require not only the geometry but also the roughness of the Earth’s surface, as well as the roughness of the objects hereon. Usually, the floodplain roughness is based on land use/land cover maps derived from orthophotos. This study analyses the applicability of roughness map derivation approaches for flood simulations based on different datasets: orthophotos, LiDAR data, official land use data, OpenStreetMap data and CORINE Land Cover data. Object-based image analysis is applied to orthophotos and LiDAR raster data in order to generate land cover maps, which enable a roughness parameterization. The vertical vegetation structure within the LiDAR point cloud is used to derive an additional floodplain roughness map. Further roughness maps are derived from official land use data, OpenStreetMap and CORINE Land Cover datasets. Six different flood simulations are applied based on one elevation data but with the different roughness maps. The results of the hydrodynamic–numerical models include information on flow velocity and water depth from which the additional attribute flood intensity is calculated of. The results based on roughness maps derived from LiDAR data and OpenStreetMap data are comparable, whereas the results of the other datasets differ significantly.
    Electronic ISSN: 2072-4292
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by MDPI Publishing
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