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  • 1
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    Prolyl hydroxylation of RPS23 by OGFOD1 [Biochemistry] (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-03-19
    Description: 2-Oxoglutarate (2OG) and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1) is predicted to be a conserved 2OG oxygenase, the catalytic domain of which is related to hypoxia-inducible factor prolyl hydroxylases. OGFOD1 homologs in yeast are implicated in diverse cellular functions ranging from oxygen-dependent regulation of sterol response genes (Ofd1, Schizosaccharomyces pombe)...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-08-19
    Description: Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frezza, Christian -- Zheng, Liang -- Folger, Ori -- Rajagopalan, Kartik N -- MacKenzie, Elaine D -- Jerby, Livnat -- Micaroni, Massimo -- Chaneton, Barbara -- Adam, Julie -- Hedley, Ann -- Kalna, Gabriela -- Tomlinson, Ian P M -- Pollard, Patrick J -- Watson, Dave G -- Deberardinis, Ralph J -- Shlomi, Tomer -- Ruppin, Eytan -- Gottlieb, Eyal -- 090532/Wellcome Trust/United Kingdom -- DK072565-05/DK/NIDDK NIH HHS/ -- WT091112MA/Wellcome Trust/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2011 Aug 17;477(7363):225-8. doi: 10.1038/nature10363.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21849978" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bilirubin/metabolism ; Cell Line ; Cells, Cultured ; Citric Acid Cycle ; Computer Simulation ; Fumarate Hydratase/deficiency/*genetics/*metabolism ; Fumarates/metabolism ; Genes, Lethal/*genetics ; *Genes, Tumor Suppressor ; Glutamine/metabolism ; Heme/metabolism ; Heme Oxygenase (Decyclizing)/antagonists & inhibitors/*genetics/*metabolism ; Kidney Neoplasms/drug therapy/enzymology/genetics/metabolism ; Leiomyomatosis/congenital/drug therapy/enzymology/genetics/metabolism ; Mice ; Mitochondria/metabolism ; Mutation/*genetics ; NAD/metabolism ; Neoplastic Syndromes, Hereditary ; Skin Neoplasms ; Uterine Neoplasms
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Cancer. Puzzling patterns of predisposition (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pollard, Patrick J -- Ratcliffe, Peter J -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):192-4. doi: 10.1126/science.1173362.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK. pjr@well.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359573" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Arginine/genetics ; Brain Neoplasms/*genetics/metabolism ; Citric Acid Cycle ; Dinucleoside Phosphates/genetics ; Fumarate Hydratase/genetics/metabolism ; *Genes, Tumor Suppressor ; *Genetic Predisposition to Disease ; Glioblastoma/*genetics/metabolism ; Glutamates/metabolism ; Humans ; Hydroxylation ; Hypoxia-Inducible Factor 1/*metabolism ; Isocitrate Dehydrogenase/*genetics/metabolism ; Mutation ; NADP/metabolism ; *Oncogenes ; Succinate Dehydrogenase/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
    Electronic Resource
    Electronic Resource
    Origin of CO2-rich fluid inclusions in synorogenic veins from the Eastern Mount Isa Fold Belt, NW Queensland, and their implications for mineralization (1999)
    Springer
    Mineralium deposita 34 (1999), S. 395-404 
    Details
    ISSN: 1432-1866
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Synorogenic veins from the Proterozoic Eastern Mount Isa Fold Belt contain three different types of fluid inclusions: CO2-rich, aqueous two-phase and rare multiphase. Inclusions of CO2 without a visible H2O phase are particularly common. The close association of CO2-rich inclusions with aqueous two-phase, and possibly multiphase inclusions suggests that phase separation of low- to -moderate salinity CO2-rich hydrothermal fluids led to the selective entrapment of the CO2. Microthermometric results indicate that CO2-rich inclusions homogenize between –15.5 and +29.9 °C which corresponds to densities of 0.99 to 0.60 g.cm−3. The homogenization temperatures of the associated aqueous two-phase inclusions are 127–397 °C, with salinities of 0.5 to 18.1 wt.% NaCl equivalent. The rarely observed multiphase inclusions homogenize between 250 and 350 °C, and have salinities ranging from 34.6 to 41.5 wt.% NaCl equivalent. Evidence used to support the presence of fluid immiscibility in this study is mainly derived from observations of coexisting H2O-rich and CO2-rich inclusions in groups and along the same trail. In addition, these two presumably unmixed fluids are also found on adjacent fractures where monophase CO2-rich inclusions are closely related to H2O-rich inclusions. Similar CO2-rich inclusions are widespread in mineral deposits in this region, which are simply metal-enriched synorogenic veins. Therefore, we argue that fluid immiscibility caused volatile species such as CO2 and H2S to be lost from liquid, thus triggering ore deposition by increasing the fluid pH and decreasing the availability of complexing ligands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001260050212
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  • 5
    Electronic Resource
    Electronic Resource
    Contrasting evolution of fluorine- and boron-rich tin systems (1987)
    Springer
    Mineralium deposita 22 (1987), S. 315-321 
    Details
    ISSN: 1432-1866
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Individual Sn provinces or regions within provinces are sometimes enriched in fluorine or boron, giving rise to fluorine-rich and boron-rich environments. The structural styles of mineralisation within these environments are similar except that hydrothermal intrusive breccia pipes are more common in boron-rich environments and apogranite/massive greisen systems are more common in fluorine-rich environments. The increased solubility of H2O in B-bearing magmas compared to F-bearing magmas may play a role in the structural evolution of the mineralising systems. The greater mechanical energy produced during crystallisation of B-rich magmas provides a mechanism for breccia pipe and stockwork formation, while the more passive crystallisation of F-rich magmas often results in the formation of disseminated mineralisation. The partitioning of boron toward the aqueous fluid phase and the enhanced solubility of silica in the fluid phase frequently results in tourmalinisation and silicification of the wall-rocks in B-rich environments. In contrast, feldspathic and sericitic alterations usually predominate in F-rich environments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00204525
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  • 6
    Electronic Resource
    Electronic Resource
    Textural evidence for quartz and feldspar dissolution as a mechanism of formation for Maggs Pipe, Zaaiplaats tin mine, South Africa (1989)
    Springer
    Mineralium deposita 24 (1989), S. 210-218 
    Details
    ISSN: 1432-1866
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Shallowly plunging and branching pipe systems in Lease and Bobbejaankop Granite at the Zaaiplaats mine are host to major tin mineralization. Detailed textural study of Maggs Pipe indicates that dissolution of the granite was a major process in the formation of open space which provided permeability for the passage of hydrothermal fluids, and sites for the precipitation of ore and gangue minerals. The pipe formation process initiates with the dissolution of granite quartz and subsequently extends to feldspar dissolution, particularly in the central portion of Maggs Pipe. Spaces created by mineral dissolution are filled by hydrothermal phases and the relict feldspar matrix becomes progressively more altered toward the centre of the pipe. The distribution of alteration and infill minerals defines a zoning pattern which, from the outer margin to the central core, includes calcite-quartz, chlorite (± cassiterite, albite, fluorite) and synchisite-calcite zones. It is postulated that quartz and feldspar dissolution resulted from interaction between the granite and hydrothermal fluids containing alkali-chloride, -fluoride or -carbonate complexes which had separated from the granite magma during crystallization. Preliminary observations on several other pipes at Zaaiplaats indicate that quartz and feldspar dissolution was a major procress in forming the pipe systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00206444
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  • 7
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    OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-02-18
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas (2014)
    Oxford University Press
    Details
    Publication Date: 2014-04-05
    Description: Malignant pheochromocytoma (PCC) and paraganglioma (PGL) are mostly caused by germline mutations of SDHB , encoding a subunit of succinate dehydrogenase. Using whole-exome sequencing, we recently identified a mutation in the FH gene encoding fumarate hydratase, in a PCC with an ‘SDH-like’ molecular phenotype. Here, we investigated the role of FH in PCC/PGL predisposition, by screening for germline FH mutations in a large international cohort of patients. We screened 598 patients with PCC/PGL without mutations in known PCC/PGL susceptibility genes. We searched for FH germline mutations and large deletions, by direct sequencing and multiplex ligation-dependent probe amplification methods. Global alterations in DNA methylation and protein succination were assessed by immunohistochemical staining for 5-hydroxymethylcytosine (5-hmC) and S-(2-succinyl) cysteine (2SC), respectively. We identified five pathogenic germline FH mutations (four missense and one splice mutation) in five patients. Somatic inactivation of the second allele, resulting in a loss of fumarate hydratase activity, was demonstrated in tumors with FH mutations. Low tumor levels of 5-hmC, resembling those in SDHB- deficient tumors, and positive 2SC staining were detected in tumors with FH mutations. Clinically, metastatic phenotype ( P = 0.007) and multiple tumors ( P = 0.02) were significantly more frequent in patients with FH mutations than those without such mutations. This study reveals a new role for FH in susceptibility to malignant and/or multiple PCC/PGL. Remarkably, FH-deficient PCC/PGLs display the same pattern of epigenetic deregulation as SDHB -mutated malignant PCC/PGL. Therefore, we propose that mutation screening for FH should be included in PCC/PGL genetic testing, at least for tumors with malignant behavior.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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    GRADE DISTRIBUTION OF THE GIANT OK TEDI Cu-Au DEPOSIT, PAPUA NEW GUINEA--A DISCUSSION (2014)
    Society of Economic Geologists (SEG)
    Details
    Publication Date: 2014-05-16
    Print ISSN: 0361-0128
    Topics: Geosciences
    Published by Society of Economic Geologists (SEG)
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  • 10
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    PARAGENESIS AND RE-OS MOLYBDENITE AGE OF THE CAMBRIAN AK-SUG PORPHYRY CU-AU-MO DEPOSIT, TYVA REPUBLIC, RUSSIAN FEDERATION (2017)
    Society of Economic Geologists (SEG)
    Details
    Publication Date: 2017-04-04
    Description: The Ak-Sug porphyry Cu-Au-Mo deposit is situated within the Altai Sayan region that forms part of the Tuva-Mongol arc of the Central Asian orogenic belt. The Ak-Sug intrusive complex is made up of a series of nested intrusions, including diorite, feldspar porphyry, quartz-feldspar porphyry, tonalite I, and tonalite II. Cu-Au-Mo mineralization occurs mainly within quartz-carbonate ± K-feldspar sulfide veins and later sericite-sulfide veins and alteration. In the northern zone, sulfide zoning consists of a central bornite core flanked by chalcopyrite and pyrite-chalcopyrite zones, with a pyrite zone on the hanging-wall side. Re-Os molybdenite dating of an early-stage quartz-carbonate ± K-feldspar sulfide vein and a late-stage molybdenite-only vein gives ages of 517.3 ± 3 and 517.4 ± 3 Ma, respectively. This indicates an Early Cambrian age for mineralization at Ak-Sug, making it one of the oldest porphyry copper deposits in the Central Asian orogenic belt. Published whole-rock geochemical data indicate that intrusive rocks at Ak-Sug and other Cambrian to Early Ordovician intrusive complexes in the Tuva-Mongol arc evolved by hornblende ± titanite fractionation due to high magmatic water contents, leading to adakite-like compositions with high Sr/Y and flat to listric-shaped rare earth element patterns that characterize many fertile arc magmas.
    Print ISSN: 0361-0128
    Topics: Geosciences
    Published by Society of Economic Geologists (SEG)
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