Genomic and in-situ Transcriptomic Characterization of the Candidate Phylum NPL-UPL2 From Highly Alkaline Highly Reducing Serpentinized Groundwater

Serpentinization is a process whereby water interacts with reduced mantle rock called peridotite to produce a new suite of minerals (e.g., serpentine), a highly alkaline fluid, and hydrogen. In previous reports, we identified abundance of microbes of the candidate phylum NPL-UPA2 in a serpentinization site called The Cedars. Here, we report the first metagenome assembled genome (MAG) of the candidate phylum as well as the in-situ gene expression. The MAG of the phylum NPL-UPA2, named Unc8, is only about 1 Mbp and its biosynthetic properties suggest it should be capable of independent growth. In keeping with the highly reducing niche of Unc8, its genome encodes none of the known oxidative stress response genes including superoxide dismutases. With regard to energy metabolism, the MAG of Unc8 encodes all enzymes for Wood-Ljungdahl acetogenesis pathway, a ferredoxin:NAD+ oxidoreductase (Rnf) and electron carriers for flavin-based electron bifurcation (Etf, Hdr). Furthermore, the transcriptome of Unc8 in the waters of The Cedars showed enhanced levels of gene expression in the key enzymes of the Wood-Ljungdahl pathway [e.g., Carbon monoxide dehydrogenase /Acetyl-CoA synthase complex (CODH/ACS), Rnf, Acetyl-CoA synthetase (Acd)], which indicated that the Unc8 is an acetogen. However, the MAG of Unc8 encoded no well-known hydrogenase genes, suggesting that the energy metabolism of Unc8 might be focused on CO as the carbon and energy sources for the acetate formation. Given that CO could be supplied via abiotic reaction associated with deep subsurface serpentinization, while available CO2 would be at extremely low concentrations in this high pH environment, CO-associated metabolism could provide advantageous approach. The CODH/ACS in Unc8 is a Bacteria/Archaea hybrid type of six-subunit complex and the electron carriers, Etf and Hdr, showed the highest similarity to those in Archaea, suggesting that archaeal methanogenic energy metabolism was incorporated into the bacterial acetogenesis in NPL-UPA2. Given that serpentinization systems are viewed as potential habitats for early life, and that acetogenesis via the Wood-Ljungdahl pathway is proposed as an energy metabolism of Last Universal Common Ancestor, a phylogenetically distinct acetogen from an early earth analog site may provide important insights in primordial lithotrophs and their habitat

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Contains reports on two research projects.Center for Advanced Television StudiesDARPA/U.S. Navy - Office of Naval Research (Contract MDA-972-88-K-0008)DARPA/U.S. Navy - Office of Naval Research (Contract N00014-85-K-0213

Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study

We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged ,18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P 5 .035). For children with verified FHL (family history/genetically verified, n 5 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n 5 53) was significantly lower (52%; 95% CI, 38-65) (P 5 .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival.Fil: Bergsten, Elisabet. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Horne, AnnaCarin. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Hed Myrberg, Ida. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Aricó, Maurizio. Children Hospital Giovanni XXIII; ItaliaFil: Astigarraga, Itziar. Universidad del País Vasco; EspañaFil: Ishii, Eiichi. Ehime University; JapónFil: Janka, Gritta. Universitat Hamburg; AlemaniaFil: Ladisch, Stephan. Children’s National Medical Center; Estados UnidosFil: Lehmberg, Kai. Universitat Hamburg; AlemaniaFil: McClain, Kenneth L.. Baylor College of Medicine; Estados UnidosFil: Minkov, Milen. Universidad de Viena; AustriaFil: Nanduri, Vasanta. Watford General Hospital; Reino UnidoFil: Rosso, Diego. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sieni, Elena. Universitaria A. Meyer Children Hospital; ItaliaFil: Winiarski, Jacek. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Henter, Jan Inge. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

Functionally Stable and Phylogenetically Diverse Microbial Enrichments from Microbial Fuel Cells during Wastewater Treatment

Microbial fuel cells (MFCs) are devices that exploit microorganisms as biocatalysts to recover energy from organic matter in the form of electricity. One of the goals of MFC research is to develop the technology for cost-effective wastewater treatment. However, before practical MFC applications are implemented it is important to gain fundamental knowledge about long-term system performance, reproducibility, and the formation and maintenance of functionally-stable microbial communities. Here we report findings from a MFC operated for over 300 days using only primary clarifier effluent collected from a municipal wastewater treatment plant as the microbial resource and substrate. The system was operated in a repeat-batch mode, where the reactor solution was replaced once every two weeks with new primary effluent that consisted of different microbial and chemical compositions with every batch exchange. The turbidity of the primary clarifier effluent solution notably decreased, and 97% of biological oxygen demand (BOD) was removed after an 8–13 day residence time for each batch cycle. On average, the limiting current density was 1000 mA/m2, the maximum power density was 13 mW/m2, and coulombic efficiency was 25%. Interestingly, the electrochemical performance and BOD removal rates were very reproducible throughout MFC operation regardless of the sample variability associated with each wastewater exchange. While MFC performance was very reproducible, the phylogenetic analyses of anode-associated electricity-generating biofilms showed that the microbial populations temporally fluctuated and maintained a high biodiversity throughout the year-long experiment. These results suggest that MFC communities are both self-selecting and self-optimizing, thereby able to develop and maintain functional stability regardless of fluctuations in carbon source(s) and regular introduction of microbial competitors. These results contribute significantly toward the practical application of MFC systems for long-term wastewater treatment as well as demonstrating MFC technology as a useful device to enrich for functionally stable microbial populations

Bioelectrochemical Stimulation of Electromethanogenesis at a Seawater-Based Subsurface Aquifer in a Natural Gas Field

In subsurface anoxic environments, microbial communities generally produce methane as an end-product to consume organic compounds. This metabolic function is a source of biogenic methane in coastal natural gas aquifers, submarine mud volcanoes, and methane hydrates. Within the methanogenic communities, hydrogenotrophic methanogens, and syntrophic bacteria are converting volatile fatty acids to methane syntrophically via interspecies hydrogen transfer. Recently, direct interspecies electron transfer (DIET) between fermentative/syntrophic bacteria and electrotrophic methanogens has been proposed as an effective interspecies metabolite transfer process to enhance methane production. In this study, in order to stimulate the DIET-associated methanogenic process at deep biosphere-aquifer systems in a natural gas field, we operated a bioelectrochemical system (BES) to apply voltage between an anode and a cathode. Two single-chamber BESs were filled with seawater-based formation water collected from an onshore natural gas well, repeatedly amended with acetate, and operated with 600 mV between electrodes for 21 months, resulting in a successful conversion of acetate to methane via electrical current consumption. One reactor yielded a stable current of ~200 mA/m2 with a coulombic efficiency (CE) of >90%; however, the other reactor, which had been incidentally disconnected for 3 days, showed less electromethanogenic activity with a CE of only ~10%. The 16S rRNA gene-based community analyses showed that two methanogenic archaeal families, Methanocalculaceae and Methanobacteriaceae, were abundant in cathode biofilms that were mainly covered by single-cell-layered biofilm, implicating them as key players in the electromethanogenesis. In contrast, family Methanosaetaceae was abundant at both electrodes and the electrolyte suspension only in the reactor with less electromethanogenesis, suggesting this family was not involved in electromethanogenesis and became abundant only after the no-electron-flow event. The anodes were covered by thick biofilms with filamentous networks, with the family Desulfuromonadaceae dominating in the early stage of the operation. The family Geobacteraceae (mainly genus Geoalkalibacter) became dominant during the longer-term operation, suggesting that these families were correlated with electrode-respiring reactions. These results indicate that the BES reactors with voltage application effectively activated a subsurface DIET-related methanogenic microbiome in the natural gas field, and specific electrogenic bacteria and electromethanogenic archaea were identified within the anode and/or cathode biofilms

Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism.

Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.We thank Kaori Yoshida, Keiko Uchiyama, Satomi Kawai, Naomi Hatanaka, Yoko Sawaguchi, Runa Washio, Takako Ichihashi, Nanako Koike, Keiko Uchiyama, Masaaki Nameta (Niigata University), Kaori Igarashi, Kaori Saitoh, Keiko Endo, Hiroko Maki, Ayano Ueno, Maki Ohishi, Sanae Yamanaka, Noriko Kagata (Keio University) for their excellent technical assistance, C. Ronald Kahn (Joslin Diabetes Center and Harvard Medical School) for providing the BAT cell line, Evan Rosen (Harvard Medical School) for providing us Ucp-Cre mice, Kosuke Morikawa (Kyoto University), Tomitake Tsukihara (University of Hyogo) and Shinya Yoshikawa (University of Hyogo) for their professional opinions and suggestions. Tis work was supported by a Grant-in-Aid for Scientifc Research (A) (20H00533) from MEXT, AMED under Grant Numbers JP20ek0210114, and AMED-CREST under Grant Number JP20gm1110012, and Moonshot Research and Development Program (21zf0127003s0201), MEXT Supported Program for the Strategic Research Foundation at Private Universities Japan, Private University Research Branding Project, and Leading Initiative for Excellent Young Researchers, and grants from the Takeda Medical Research Foundation, the Vehicle Racing Commemorative Foundation, Ono Medical Research Foundation, and the Suzuken Memorial Foundation (to T.M.). Support was also provided by a Grants-in-Aid for Young Scientists (Start-up) (26893080), and grants from the Uehara Memorial Foundation, Kowa Life Science Foundation, Manpei Suzuki Diabetes Foundation, SENSHIN Medical Research Foundation, ONO Medical Research Foundation, Tsukada Grant for Niigata University Medical Research, Te Nakajima Foundation, SUZUKEN memorial foundation, HOKUTO Corporation, Mochida Memorial Foundation for Medical & Pharmaceutical Research, Grants-in-Aid for Encouragement of Young Scientists (A) (16H06244), Daiichi Sankyo Foundation of Life Science, AMED Project for Elucidating and Controlling Mechanisms of Aging and Longevity under Grant Number JP17gm5010002, JP18gm5010002, JP19gm5010002, JP20gm5010002, JP21gm5010002, Astellas Foundation for Research on Metabolic Disorders, Research grant from Naito Foundation, Te Japan Geriatrics Society (to I.S.); by a Grant-in-Aid for Scientifc Research (C) (19K08974), Yujin Memorial Grant, Sakakibara Memorial Research Grant from Te Japan Research Promotion Society for Cardiovascular Diseases, TERUMO Life Science Foundation, Kanae Foundation (to Y.Y.), JST ERATO (JPMJER1902), AMED-CREST (JP20gm1010009), the Takeda Science Foundation, the Food Science Institute Foundation (to S.F.), and by a grant from Bourbon (to T.M., I.S. and Y.Y.).S

Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV

The effects of the final state interaction phenomenon known as colour reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~ 189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to affect observables based on charged particles in hadronic decays of W+W-. Measurements of inclusive charged particle multiplicities, and of their angular distribution with respect to the four jet axes of the events, are used to test models of colour reconnection. The data are found to exclude extreme scenarios of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other models, both with and without colour reconnection effects. In the context of the SK-I model, the best agreement with data is obtained for a reconnection probability of 37%. Assuming no colour reconnection, the charged particle multiplicity in hadronically decaying W bosons is measured to be (nqqch) = 19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2

The hadronic structure function of the photon F_2^gamma is measured as a function of Bjorken x and of the factorisation scale Q^2 using data taken by the OPAL detector at LEP. Previous OPAL measurements of the x dependence of F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted by QCD, the data show positive scaling violations in F_2^gamma. Several parameterisations of F_2^gamma are in agreement with the measurements whereas the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001, Ascona, Switzerlan

Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure