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  • 1
    Electronic Resource
    Electronic Resource
    In vitro evidence for dose-dependent cytotoxicity as the predominant effect of low dose Ara-C on human leukemic and normal marrow cells (1989)
    Springer
    Cancer chemotherapy and pharmacology 23 (1989), S. 87-94 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine whether cytosine arabinoside (Ara-C) has a differentiating effect in vitro, marrow cells from nine patients with acute non-lymphocytic leukemia or myelodysplastic syndrome and eight non-leukemic controls were exposed to drug concentrations comparable to those achieved in vivo with low-dose Ara-C therapy. In soft agar cultures, the predominant effect of Ara-C at concentrations between 10-8 M and 10-6 M was cytotoxicity with a dose-dependent decrement in Colony Forming Unit of the granulocyte and monocyte lineage (CFUg/m) at 14 days. Growth in liquid cultures containing Giant Cell Tumor(GCT)-conditioned media without Ara-C resulted in a significant increment in the recovery of mature cells at day 10 from the non-leukemic cultures (P=0.03), while only a minor increase was found in the leukemic cultures (P=0.09). All liquid cultures exposed to ≽10-9 M Ara-C showed a marked reduction in the immature proliferating cell pool, with a concomitant increase in the percentage of mature non-dividing cells at 10 days. However, the absolute number of differentiated cells recovered remained constant or decreased in all non-leukemic and eight of nine leukemic cultures, compared with cultures without Ara-C. Enhanced recovery of differentiated cells was also never observed in any culture exposed to the relatively non-toxic 10-9 M Ara-C. These in vitro findings support clinical observations suggesting that cytotoxicity rather than differentiation is the major mechanism involved in the therapeutic effect of low-dose Ara-C in acute leukemia and myelodysplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273523
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  • 2
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    Mariprofundus ferrooxydans PV-1 the First Genome of a Marine Fe(II) Oxidizing Zetaproteobacterium (2011)
    Public Library of Science
    Details
    Publication Date: 2022-05-25
    Description: © The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e25386, doi:10.1371/journal.pone.0025386.
    Description: Mariprofundus ferrooxydans PV-1 has provided the first genome of the recently discovered Zetaproteobacteria subdivision. Genome analysis reveals a complete TCA cycle, the ability to fix CO2, carbon-storage proteins and a sugar phosphotransferase system (PTS). The latter could facilitate the transport of carbohydrates across the cell membrane and possibly aid in stalk formation, a matrix composed of exopolymers and/or exopolysaccharides, which is used to store oxidized iron minerals outside the cell. Two-component signal transduction system genes, including histidine kinases, GGDEF domain genes, and response regulators containing CheY-like receivers, are abundant and widely distributed across the genome. Most of these are located in close proximity to genes required for cell division, phosphate uptake and transport, exopolymer and heavy metal secretion, flagellar biosynthesis and pilus assembly suggesting that these functions are highly regulated. Similar to many other motile, microaerophilic bacteria, genes encoding aerotaxis as well as antioxidant functionality (e.g., superoxide dismutases and peroxidases) are predicted to sense and respond to oxygen gradients, as would be required to maintain cellular redox balance in the specialized habitat where M. ferrooxydans resides. Comparative genomics with other Fe(II) oxidizing bacteria residing in freshwater and marine environments revealed similar content, synteny, and amino acid similarity of coding sequences potentially involved in Fe(II) oxidation, signal transduction and response regulation, oxygen sensation and detoxification, and heavy metal resistance. This study has provided novel insights into the molecular nature of Zetaproteobacteria.
    Description: Funding has been provided by the NSF Microbial Observatories Program (KJE, DE), NSF’s Science and Technology Program, by the Gordon and Betty Moore Foundation (KJE), the College of Letters, Arts, and Sciences at the University of Southern California (KJE), and by the NASA Astrobiology Institute (KJE, DE). Advanced Light Source analyses at the Lawrence Berkeley National Lab are supported by the Office of Science, Basic Energy Sciences, Division of Materials Science of the United States Department of Energy (DE-AC02-05CH11231).
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 3
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    Characterization of cytochrome 579, an unusual cytochrome isolated from an iron-oxidizing microbial community (2009)
    American Society for Microbiology
    Details
    Publication Date: 2022-05-25
    Description: Author Posting. © American Society for Microbiology, 2008. This article is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 74 (2008): 4454-4462, doi:10.1128/AEM.02799-07.
    Description: A novel, soluble cytochrome with an unusual visible spectral signature at 579 nm (Cyt579) has been characterized after isolation from several different microbial biofilms collected in an extremely acidic ecosystem. Previous proteogenomic studies of an Fe(II)-oxidizing community indicated that this abundant red cytochrome could be extracted from the biofilms with dilute sulfuric acid. Here, we found that the Fe(II)-dependent reduction of Cyt579 was thermodynamically favorable at a pH of 〉3, raising the possibility that Cyt579 acts as an accessory protein for electron transfer. The results of transmission electron microscopy of immunogold-labeled biofilm indicated that Cyt579 is localized near the bacterial cell surface, consistent with periplasmic localization. The results of further protein analysis of Cyt579, using preparative chromatofocusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed three forms of the protein that correspond to different N-terminal truncations of the amino acid sequence. The results of intact-protein analysis corroborated the posttranslational modifications of these forms and identified a genomically uncharacterized Cyt579 variant. Homology modeling was used to predict the overall cytochrome structure and heme binding site; the positions of nine amino acid substitutions found in three Cyt579 variants all map to the surface of the protein and away from the heme group. Based on this detailed characterization of Cyt579, we propose that Cyt579 acts as an electron transfer protein, shuttling electrons derived from Fe(II) oxidation to support critical metabolic functions in the acidophilic microbial community.
    Description: Funding was provided by the U.S. Department of Energy, Office of Science, from the Genomics: GTL Program, grant DE-FG02-05ER64134, to J.F.B., R.L.H., and M.P.T. Work at LLNL was performed under the auspices of the U.S. Department of Energy under contract DE-AC52-07NA27344.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 4
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    Ultra-diffuse hydrothermal venting supports Fe-oxidizing bacteria and massive umber deposition at 5000 m off Hawaii (2012)
    Nature Publishing Group
    Details
    Publication Date: 2022-05-25
    Description: © International Society for Microbial Ecology, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 5 (2011): 1748–1758, doi:10.1038/ismej.2011.48.
    Description: A novel hydrothermal field has been discovered at the base of Lōihi Seamount, Hawaii, at 5000 mbsl. Geochemical analyses demonstrate that ‘FeMO Deep’, while only 0.2 °C above ambient seawater temperature, derives from a distal, ultra-diffuse hydrothermal source. FeMO Deep is expressed as regional seafloor seepage of gelatinous iron- and silica-rich deposits, pooling between and over basalt pillows, in places over a meter thick. The system is capped by mm to cm thick hydrothermally derived iron-oxyhydroxide- and manganese-oxide-layered crusts. We use molecular analyses (16S rDNA-based) of extant communities combined with fluorescent in situ hybridizations to demonstrate that FeMO Deep deposits contain living iron-oxidizing Zetaproteobacteria related to the recently isolated strain Mariprofundus ferroxydans. Bioenergetic calculations, based on in-situ electrochemical measurements and cell counts, indicate that reactions between iron and oxygen are important in supporting chemosynthesis in the mats, which we infer forms a trophic base of the mat ecosystem. We suggest that the biogenic FeMO Deep hydrothermal deposit represents a modern analog for one class of geological iron deposits known as ‘umbers’ (for example, Troodos ophilolites, Cyprus) because of striking similarities in size, setting and internal structures.
    Description: Funding has been provided by the NSF Microbial Observatories Program (KJE, DE, BT, HS and CM), by the Gordon and Betty Moore Foundation (KJE), the College of Letters, Arts, and Sciences at the University of Southern California (KJE) and by the NASA Astrobiology Institute (KJE, DE).
    Keywords: Geomicrobiology ; Deep biosphere ; Hydrothermal ; Iron bacteria ; Iron oxidation
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/vnd.ms-excel
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  • 5
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    A novel lineage of proteobacteria involved in formation of marine Fe-oxidizing microbial mat communities (2011)
    Public Library of Science
    Details
    Publication Date: 2022-05-26
    Description: © The Authors, 2007. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 2 (2007): e667, doi:10.1371/journal.pone.0000667.
    Description: For decades it has been recognized that neutrophilic Fe-oxidizing bacteria (FeOB) are associated with hydrothermal venting of Fe(II)-rich fluids associated with seamounts in the world's oceans. The evidence was based almost entirely on the mineralogical remains of the microbes, which themselves had neither been brought into culture or been assigned to a specific phylogenetic clade. We have used both cultivation and cultivation-independent techniques to study Fe-rich microbial mats associated with hydrothermal venting at Loihi Seamount, a submarine volcano. Using gradient enrichment techniques, two iron-oxidizing bacteria, strains PV-1 and JV-1, were isolated. Chemolithotrophic growth was observed under microaerobic conditions; Fe(II) and Fe0 were the only energy sources that supported growth. Both strains produced filamentous stalk-like structures composed of multiple nanometer sized fibrils of Fe-oxyhydroxide. These were consistent with mineralogical structures found in the iron mats. Phylogenetic analysis of the small subunit (SSU) rRNA gene demonstrated that strains PV-1 and JV-1 were identical and formed a monophyletic group deeply rooted within the Proteobacteria. The most similar sequence (85.3% similarity) from a cultivated isolate came from Methylophaga marina. Phylogenetic analysis of the RecA and GyrB protein sequences confirmed that these strains are distantly related to other members of the Proteobacteria. A cultivation-independent analysis of the SSU rRNA gene by terminal-restriction fragment (T-RF) profiling showed that this phylotype was most common in a variety of microbial mats collected at different times and locations at Loihi. On the basis of phylogenetic and physiological data, it is proposed that isolate PV-1T ( = 1ATCC BAA-1019: JCM 14766) represents the type strain of a novel species in a new genus, Mariprofundus ferrooxydans gen. nov., sp. nov. Furthermore, the strain is the first cultured representative of a new candidatus class of the Proteobacteria that is widely distributed in deep-sea environments, Candidatus ζ (zeta)-Proteobacteria cl. nov.
    Description: Funding was provided to DE and CLM by the National Science Foundation (0348330) and to DE through the NASA Astobiology Institute.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 6
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    Hydrothermal vents as a kinetically stable source of iron-sulphide-bearing nanoparticles to the ocean (2011)
    Nature Publishing Group
    In:  Nature Geoscience, 4 (6). pp. 367-371.
    Details
    Publication Date: 2016-04-27
    Description: Hydrothermal vents emit sulphur and metals to the ocean1. Particular attention has been paid to hydrothermal fluxes of iron2–4, a limiting micronutrient of marine primary production5. Vent-derived ironwas previously thought to rapidly oxidize and precipitate around vents6. However, organic matter can bind to and stabilize dissolved and particulate iron in hydrothermal plumes7–9, facilitating its dispersion into the open ocean10. Here, we report measurements of the chemical speciation of sulphide and iron in high-temperature fluids emanating from vents in the East Pacific Rise and the Eastern Lau Spreading Center. We show that pyrite nanoparticles—composed of iron and sulphur—account for up to 10% of the filterable iron (less than 200nm in size) in these fluids. We suggest that these particles form before the discharge of the vent fluid. We estimate that pyrite nanoparticles sink more slowly than larger plume particles, and are more resistant to oxidation than dissolved Fe(II) and FeS.We suggest that the discharge of iron in the form of pyrite nanoparticles increases the probability that vent-derived iron will be transported over long distances in the deep ocean.
    Type: Article , PeerReviewed
    Format: text
    DOI: 10.1038/ngeo1148
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    OceanRep: Article in a Scientific Journal - peer-reviewed
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