175 research outputs found

    Osmium uptake, distribution, and 187Os/188Os and 187Re/188Os compositions in Phaeophyceae macroalgae, Fucus vesiculosus: Implications for determining the 187Os/188Os composition of seawater

    Get PDF
    The osmium isotopic composition (187Os/188Os) of seawater reflects the balance of input from mantle-, continental- and anthropogenic-derived sources. This study utilizes the Phaeophyceae, Fucus vesiculosus, to analyse its Os abundance and uptake, as well as to assess if macroalgae records the Os isotope composition of the seawater in which it lives. The data demonstrates that Os is not located in one specific biological structure within macroalgae, but is found throughout the organism. Osmium uptake was measured by culturing F. vesiculosus non-fertile tips with different concentrations of Os with a known 187Os/188Os composition (∼0.16), which is significantly different from the background isotopic composition of local seawater (∼0.94). The Os abundance of cultured non-fertile tips show a positive correlation to the concentration of the Os doped seawater. Moreover, the 187Os/188Os composition of the seaweed equaled that of the culture medium, stongly confirming the possible use of macroalgae as a biological proxy for the Os isotopic composition of the seawater

    Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

    Get PDF
    Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors

    Multi-objective Optimization of Thermophilic Biohydrogen Production

    Get PDF
    Dynamic optimization of thermophilic hydrogen and by-product production requires the use of robust models coupled with control strategies. In this work, a model was used to optimize biohydrogen (bioH2) and acetate production using Thermotoga maritima (T. maritima) with a Multi-Objective Optimization (MOO). The aim was to find the trade-off between the maxima of yield and productivity of the hydrogen production and acetate in a continuous dark fermentation process by modifying the inlet liquid flow rate. A dynamic mass balance model was used to optimize thermophilic bioH2 and acetate production using T. maritima MSB8 (DSMZ 3109) strains.

    Strontium isotopes in Chilean rivers : the flux of unradiogenic continental Sr to seawater

    Get PDF
    Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Chemical Geology 268 (2009): 337-343, doi:10.1016/j.chemgeo.2009.09.013.Analyses of Chilean river waters indicate that the average yield of unradiogenic Sr (~ 517 mol Sr km− 2 yr− 1, 87Sr/86Sr ~ 0.7057) from western South America (1,220,853 km2) into the southeastern Pacific Ocean is ~ 2–4 times higher than that from Iceland (~ 110 mol Sr km − 2 yr− 1, 87Sr/86Sr ~ 0.7025) and the Deccan traps, but lower than fluxes of unradiogenic Sr from ocean islands in the Lesser Antilles and Réunion. The Sr flux from western South America accounts for about 1.8% of the annual dissolved Sr delivered to the ocean via rivers. If Chilean rivers analyzed in this study accurately characterize runoff from western South America, active convergent continental margins release about as much unradiogenic Sr to seawater as a 0–1 Myr old mid-ocean ridge segment of equivalent length. Modulations of the flux of unradiogenic Sr from active margins over geologic time scales have to be considered as an additional driving force of change in the marine Sr isotope record, supplementing temporal variations in the submarine hydrothermal flux as a source of unradiogenic Sr to seawater. Such modulations can be driven by changes in the surface exposure of volcanic arc terrains, changes in climate, ocean currents and geographic latitude due to plate tectonics, as well as topographic changes that can affect local rainfall, runoff and erosion.We acknowledge financial 302 support from NSF grant EAR-0519387, from WHOI’s Mary Sears Visitor Program, and thank the German DAAD for travel support for KF

    Expression of P. falciparum var Genes Involves Exchange of the Histone Variant H2A.Z at the Promoter

    Get PDF
    Plasmodium falciparum employs antigenic variation to evade the human immune response by switching the expression of different variant surface antigens encoded by the var gene family. Epigenetic mechanisms including histone modifications and sub-nuclear compartmentalization contribute to transcriptional regulation in the malaria parasite, in particular to control antigenic variation. Another mechanism of epigenetic control is the exchange of canonical histones with alternative variants to generate functionally specialized chromatin domains. Here we demonstrate that the alternative histone PfH2A.Z is associated with the epigenetic regulation of var genes. In many eukaryotic organisms the histone variant H2A.Z mediates an open chromatin structure at promoters and facilitates diverse levels of regulation, including transcriptional activation. Throughout the asexual, intraerythrocytic lifecycle of P. falciparum we found that the P. falciparum ortholog of H2A.Z (PfH2A.Z) colocalizes with histone modifications that are characteristic of transcriptionally-permissive euchromatin, but not with markers of heterochromatin. Consistent with this finding, antibodies to PfH2A.Z co-precipitate the permissive modification H3K4me3. By chromatin-immunoprecipitation we show that PfH2A.Z is enriched in nucleosomes around the transcription start site (TSS) in both transcriptionally active and silent stage-specific genes. In var genes, however, PfH2A.Z is enriched at the TSS only during active transcription in ring stage parasites. Thus, in contrast to other genes, temporal var gene regulation involves histone variant exchange at promoter nucleosomes. Sir2 histone deacetylases are important for var gene silencing and their yeast ortholog antagonises H2A.Z function in subtelomeric yeast genes. In immature P. falciparum parasites lacking Sir2A or Sir2B high var transcription levels correlate with enrichment of PfH2A.Z at the TSS. As Sir2A knock out parasites mature the var genes are silenced, but PfH2A.Z remains enriched at the TSS of var genes; in contrast, PfH2A.Z is lost from the TSS of de-repressed var genes in mature Sir2B knock out parasites. This result indicates that PfH2A.Z occupancy at the active var promoter is antagonized by PfSir2A during the intraerythrocytic life cycle. We conclude that PfH2A.Z contributes to the nucleosome architecture at promoters and is regulated dynamically in active var genes

    Rhenium-osmium isotope and elemental behaviour during subduction of oceanic crust and the implications for mantle recycling

    No full text
    This study presents major-, trace-element, and rhenium-osmium (Re-Os) isotope and elemental data for basalts and gabbros from the Zermatt-Saas ophiolite, metamorphosed to eclogite-facies conditions during the Alpine orogeny. Igneous crystallisation of the gabbros occurred at 163.5 +/- 1.8 Ma and both gabbro and basalt were subject to 'peak' pressure-temperature (P-T) conditions of > 2.0 GPa and similar to 600 degrees C at about 40.6 +/- 2.6 Ma. Despite such extreme P-T conditions, Re-Os isotope and abundance data for gabbroic rocks suggest that there has been no significant loss of either of these elements during eclogite-facies metamorphism. Indeed, Re-187-Os-187 isotope data for both unaltered gabbros and gabbroic eclogites lie on the same best-fit line corresponding to an errorchron age of 160 +/- 6 Ma, indistinguishable from the age of igneous crystallisation. In contrast, metamorphosed basalts do not yield age information; rather most possess Re-187/Os-188 ratios that cannot account for the measured Os-187/Os-188 ratios, given the time since igneous crystallisation. Taken with their low Re contents these data indicate that the basalts have experienced significant Re loss (similar to 50-60%), probably during high-pressure metamorphism. Barium, Rb and K are depleted in both gabbroic and basaltic eclogites. In contrast, there is no evident depletion of U in either lithology. Many ocean-island basalts (OIB) possess radiogenic Os and Pb isotope compositions that have been attributed to the presence of recycled oceanic crust in the mantle source. Published Re-Os data for high-P metabasaltic rocks alone (consistent with this study) have been taken to suggest that excessive amounts of oceanic crust are required to generate such signatures. However, this study shows that gabbro may exert a strong influence on the composition of recycled oceanic crust. Using both gabbro and basalt (i.e. a complete section of oceanic crust) calculations suggest that the presence of >= 40% of 2 Ga oceanic crust can generate the radiogenic Os compositions seen in some OIB. Furthermore, lower U/Pb ratios in gabbro (compared to basalt) serve to limit the (PbPb)-Pb-206-Pb-204 ratios generated, while having a minimal effect on Os ratios. These results suggest that the incorporation of gabbro into recycling models provides a means of producing a range of OIB compositions having lower (and variable) Pb-206/Ph-204 ratios, but still preserving Os-187/Os-188 compositions comparable to HIMU-type OIB
    • …
    corecore