Carbon and mineral transformations in seafloor serpentinization systems

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2018This thesis examines abiotic processes controlling the transformation and distribution of carbon compounds in seafloor hydrothermal systems hosted in ultramafic rock. These processes have a direct impact on carbon budgets in the oceanic lithosphere and on the sustenance of microorganisms inhabiting hydrothermal vent ecosystems. Where mantle peridotite interacts with carbon-bearing aqueous fluids in the subseafloor, dissolved inorganic carbon can precipitate as carbonate minerals or undergo reduction by H2(aq) to form reduced carbon species. In Chapters 2 and 3, I conduct laboratory experiments to assess the relative extents of carbonate formation and CO2 reduction during alteration of peridotite by CO2(aq)-rich fluids. Results from these experiments reveal that formation of carbonate minerals is favorable on laboratory timescales, even at high H2(aq) concentrations generated by serpentinization reactions. Although CO2(aq) attains rapid metastable equilibrium with formate, formation of thermodynamically stable CH4(aq) is kinetically limited on timescales relevant for active fluid circulation in the subseafloor. It has been proposed that CH4 and potentially longer-chain hydrocarbons may be sourced, instead, from fluid inclusions hosted in plutonic and mantle rocks. Chapter 4 analyzes CH4-rich fluid inclusions in olivine-rich basement rocks from the Von Damm hydrothermal field and the Zambales ophiolite to better understand the origin of abiotic hydrocarbons in ultramaficinfluenced hydrothermal systems. Comparisons of hydrocarbon abundances and stable isotopic compositions in fluid inclusions and associated vent fluids suggest that fluid inclusions may provide a significant contribution of abiotic hydrocarbons to both submarine and continental serpentinization systems.This thesis research was funded by the National Science foundation through grants OCE- 1427274 and OCE-1634032. Louise Von Damm generously contributed financial support for research conducted in Chapter 4

Abiotic methane synthesis and serpentinization in olivine-hosted fluid inclusions

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 116(36), (2019): 17666-17672. doi:10.1073/pnas.1907871116.The conditions of methane (CH4) formation in olivine-hosted secondary fluid inclusions and their prevalence in peridotite and gabbroic rocks from a wide range of geological settings were assessed using confocal Raman spectroscopy, optical and scanning electron microscopy, electron microprobe analysis, and thermodynamic modeling. Detailed examination of 160 samples from ultraslow- to fast-spreading midocean ridges, subduction zones, and ophiolites revealed that hydrogen (H2) and CH4 formation linked to serpentinization within olivine-hosted secondary fluid inclusions is a widespread process. Fluid inclusion contents are dominated by serpentine, brucite, and magnetite, as well as CH4(g) and H2(g) in varying proportions, consistent with serpentinization under strongly reducing, closed-system conditions. Thermodynamic constraints indicate that aqueous fluids entering the upper mantle or lower oceanic crust are trapped in olivine as secondary fluid inclusions at temperatures higher than ∼400 °C. When temperatures decrease below ∼340 °C, serpentinization of olivine lining the walls of the fluid inclusions leads to a near-quantitative consumption of trapped liquid H2O. The generation of molecular H2 through precipitation of Fe(III)-rich daughter minerals results in conditions that are conducive to the reduction of inorganic carbon and the formation of CH4. Once formed, CH4(g) and H2(g) can be stored over geological timescales until extracted by dissolution or fracturing of the olivine host. Fluid inclusions represent a widespread and significant source of abiotic CH4 and H2 in submarine and subaerial vent systems on Earth, and possibly elsewhere in the solar system.We are indebted to J. Eckert for his support with FE-EMPA; to K. Aquinho and E. Codillo for providing samples from Zambales; to K. Aquinho for Raman analysis of some of the samples from Zambales and Mt. Dent; to H. Dick for providing access to his thin section collection; to the curators of the IODP core repositories for providing access to Ocean Drilling Program (ODP) and Integrated Ocean Drilling Program (IODP) samples; and to the captains and crews of the many cruises without whom the collection of these samples would not have been possible. Reviews by Peter Kelemen and an anonymous referee greatly improved this manuscript. This study is supported with funds provided by the National Science Foundation (NSF-OCE Award 1634032 to F.K. and J.S.S.).2020-02-1

Cimiracemate A confers protection on arthritic neonatal rats via regulation of iNOS/NF-κB/TLR-4 pathway

Purpose: To investigate the protective effect of cimiracemate A on Freund’s adjuvant-induced rheumatoid arthritis (RA) in neonatal rats, and the underlying mechanism. Methods: Rheumatoid arthritis was induced in rat pups using Complete Freund’s adjuvant (100 µg/100 µL/body weight) which was intra-dermally injected at the tail region. After 21 days of establishment of RA, the rats were randomly assigned to four groups of ten rats each: control group, RA group, 5 mg/kg cimiracemate A group, and 10 mg/kg cimiracemate A group. Cimiracemate A was orally administered for 45 days. The effect of cimiracemate A on oxidative stress biomarkers, superoxide dismutase (SOD), malondialdehyde (MDA) and reduced glutathione (GSH) were determined using standard methods. Plasma levels of the inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE-2) and matrix metalloproteinase-3 (MMP-3) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the levels of protein expressions of iNOS, NF-κB and TLR-4. Results: The level of MDA significantly increased and the level of GSH significantly decreased in RA group relative to control group (p < 0.05) following treatment with cimiracemate A. SOD activity was significantly reduced in RA group, when compared with control group (p < 0.05). However, treatment with cimiracemate A significantly and dose-dependently reversed the altered levels of MDA and GSH and SOD activity, when compared with RA group (p < 0.05). Plasma levels of IL-1β, TNF-α, PGE-2 and MMP-3 were significantly higher in RA group than in control group, but were significantly and dosedependently reduced after treatment with cimiracemate A (p < 0.05). There were significant increases in the levels of expression of iNOS, NF-κB and TLR-4 proteins in the chondrocytes of RA group, relative to control group (p < 0.05). However, treatment with cimiracemate A significantly and dose-dependently down-regulated the expressions of these proteins, when compared with RA group (p < 0.05). Conclusion: The results of this study indicate that cimiracemate A confers some degree of protection on arthritic neonatal rats via a mechanism that involves regulation of iNOS/NF-κB/TLR-4 pathway

Mutation analysis of KRAS and BRAF genes in metastatic colorectal cancer: A first large scale study from Iran

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6 cases (n=336). Of KRAS mutation positive cases, 85.1 were in codon 12 and 14.9 were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable

Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event : a cohort study

There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events. To determine if there is an independent association between NAFLD and CVD events. In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up. The incidence of non-fatal CVD events in males with NAFLD was significantly higher ( = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models. No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard. [Abstract copyright: ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Signal transduction pathway mutations in gastrointestinal (GI) cancers : a systematic review and meta-analysis

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3–8%), 12% (95% CI: 8–18%), 17% (95% CI: 14–20%), and 20% (95% CI: 5–41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14–33%) and 20% (95% CI, 17–24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.

Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK Cancer Research UK ERC H2020 Wellcome Trus

Flexible Adsorbents at High Pressure: Observations and Correlation of ZIF-7 Stepped Sorption Isotherms for Nitrogen, Argon, and Other Gases

© 2020 American Chemical Society. Stepped adsorption isotherms with desorption hysteresis were measured for nitrogen, argon, ethane, carbon dioxide, and methane at pressures up to 17 MPa on zeolitic imidazolate framework-7 (ZIF-7) using a gravimetric sorption analyzer. Such stepped sorption isotherms have not been previously reported for nitrogen or argon on ZIF-7, and required the application of pressures as high as 15 MPa to trigger the ZIF-7 structural phase transition at temperatures around 360 K. The stepped hysteretic sorption isotherms measured for carbon dioxide, methane, and ethane were consistent with previous observations reported in the literature. To correlate these stepped hysteretic sorption isotherms, a semi-empirical model was developed by combining a three-parameter Langmuir equation to describe the Type I aspect of the isotherm, with a model designed to describe the temperature-dependent ZIF-7 structural phase transition. Excellent fits of the combined adsorption and desorption branches were achieved by adjusting nine parameters in the temperature-dependent model, with root-mean-square deviations within 2.5 % of the highest measured adsorption capacity. Each parameter of the new semi-empirical model has a physical basis, allowing them to be estimated or compared independently

Gate opening effect of zeolitic imidazolate framework ZIF-7 for adsorption of CH4 and CO2 from N2

We report adsorption isotherms of CO2 and CH4 on the zeolitic imidazolate framework ZIF-7 that exhibit gate opening features associated with a flexible framework structure. This phenomenon has been reported by others for CO2 and light alkanes (e.g. ethane, ethylene, propane), but our study presents for first time experimental data to show that CH4 can also induce a gate opening effect in ZIF-7. Uptakes of CO2, CH4 and N2 on ZIF-7 were measured by a gravimetric adsorption apparatus at temperatures of 303-323 K and pressures up to 4494 kPa. From the CH4 isotherm measured at 303 K the transition pressure for the gate opening in ZIF-7 was estimated as 1245 kPa and the free-energy change associated with the structural phase change was 5.70 kJ mol-1. At an adsorption temperature of 303 K the phase transition pressure for CO2 in ZIF-F was 78 kPa and the free energy change was 2.43 kJ mol-1. The gate opening behaviour observed in this study shows ZIF-7 may have a potential selectivity for CH4 from N2 of more than 10 from an equimolar CH4 + N2 mixture. The equilibrium selectivity of ZIF-7 at 303 K and pressures close to 100 kPa are predicted to be 24 for CO2 from CH4 and 101 for CO2 from N2