Low Temperature Hydrogen Production and Habitability of a Hyperalkaline Serpentinite Aquifer in the Samail Ophiolite

Continental serpentinizing systems, such as the Samail Ophiolite in Oman, are excellent locations to study low-temperature water/rock reactions leading hydrogen production. Hydrogen is a strong electron donor that, along with electron acceptors such as CO2 or SO42-, can sustain microbial life. I performed experimental and analytical work with partially serpentinized peridotite from Oman to determine that Fe(II)-bearing brucite is a key reactive mineral leading to hydrogen production. At 100&deg;C and fluid compositions similar to those found in shallow serpentinizing aquifers, we experimentally observed the destabilization of Fe(II)-brucite to produce hydrogen and Fe(III)-bearing magnetite. These reactions occur quickly over a period of several months. H2 production is associated with CO2 reduction into low weight molecular acids, and perhaps solid carbonaceous material. This experimental work was paired with a field study of drill cuttings obtained from subsurface rocks in contact with serpentinizing fluids rich in H2 and CH4 at depths ranging from 17m to 262m. Mineralogical and geochemical analysis of drill cuttings showed a similar trend of decreased brucite abundance and increased magnetite formation as the rock became more altered near the surface. CH4 sampled from subsurface fluids has &delta;13C values as positive as +3&permil;. Although these &delta;13C values would traditionally be interpreted as abiotic, we believe it is possible microbial activity may contribute to the CH4 isotope values because of the presence of methanogens and methanotrophs in the subsurface fluids, as determined by 16S rRNA analysis. Thus, we isolated Methanobacterium was from the same subsurface fluids in Oman to investigate the carbon isotope fractionation factors associated with methanogenesis at high pH, probing if microbiology could be responsible for the unique isotope values found in the fluids. Carbon isotope fractionation during methanogenesis by Methanobacterium under conditions of carbon-limitation at pH ~9 is suppressed, leading to &delta;13CCH4&nbsp;values as high as -28&permil;. Such &delta;13CCH4 values may be mistakenly interpreted as abiotic based on current classifications of &ldquo;biotic&rdquo; versus &ldquo;abiotic&rdquo; methane isotopic signatures. Thus, we need to carefully evaluate the carbon cycling pathways operating in serpentinizing systems and not automatically assume abiotic or biotic origins for CH4 until the system is well characterized.</p

Low Temperature Hydrogen Production and Habitability of a Hyperalkaline Serpentinite Aquifer in the Samail Ophiolite

Continental serpentinizing systems, such as the Samail Ophiolite in Oman, are excellent locations to study low-temperature water/rock reactions leading hydrogen production. Hydrogen is a strong electron donor that, along with electron acceptors such as CO2 or SO42-, can sustain microbial life. I performed experimental and analytical work with partially serpentinized peridotite from Oman to determine that Fe(II)-bearing brucite is a key reactive mineral leading to hydrogen production. At 100°C and fluid compositions similar to those found in shallow serpentinizing aquifers, we experimentally observed the destabilization of Fe(II)-brucite to produce hydrogen and Fe(III)-bearing magnetite. These reactions occur quickly over a period of several months. H2 production is associated with CO2 reduction into low weight molecular acids, and perhaps solid carbonaceous material. This experimental work was paired with a field study of drill cuttings obtained from subsurface rocks in contact with serpentinizing fluids rich in H2 and CH4 at depths ranging from 17m to 262m. Mineralogical and geochemical analysis of drill cuttings showed a similar trend of decreased brucite abundance and increased magnetite formation as the rock became more altered near the surface. CH4 sampled from subsurface fluids has δ13C values as positive as +3‰. Although these δ13C values would traditionally be interpreted as abiotic, we believe it is possible microbial activity may contribute to the CH4 isotope values because of the presence of methanogens and methanotrophs in the subsurface fluids, as determined by 16S rRNA analysis. Thus, we isolated Methanobacterium was from the same subsurface fluids in Oman to investigate the carbon isotope fractionation factors associated with methanogenesis at high pH, probing if microbiology could be responsible for the unique isotope values found in the fluids. Carbon isotope fractionation during methanogenesis by Methanobacterium under conditions of carbon-limitation at pH ~9 is suppressed, leading to δ13CCH4 values as high as -28‰. Such δ13CCH4 values may be mistakenly interpreted as abiotic based on current classifications of “biotic” versus “abiotic” methane isotopic signatures. Thus, we need to carefully evaluate the carbon cycling pathways operating in serpentinizing systems and not automatically assume abiotic or biotic origins for CH4 until the system is well characterized

Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment