Neuregulin 1 and susceptibility to schizophrenia

To access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this pageThe cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia

The Artelon CMC spacer compared with tendon interposition arthroplasty: A randomized, controlled, multicenter study of 109 patients with osteoarthritis followed for 1 year

Background and purpose The Artelon CMC spacer is designed for surgical treatment of osteoarthritis (OA) in the carpometacarpal joint of the thumb (CMC-I). Good results using this degradable device were previously presented in a pilot study. We now present results from a larger randomized, controlled, multicenter study

Analysing the Large Decline in Coronary Heart Disease Mortality in the Icelandic Population Aged 25-74 between the Years 1981 and 2006

BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s. We examined how much of the decrease between 1981 and 2006 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors. METHODOLOGY: The previously validated IMPACT CHD mortality model was applied to the Icelandic population. The data sources were official statistics, national quality registers, published trials and meta-analyses, clinical audits and a series of national population surveys. PRINCIPAL FINDINGS: Between 1981 and 2006, CHD mortality rates in Iceland decreased by 80% in men and women aged 25 to 74 years, which resulted in 295 fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer incident MI cases per year, which is a major determinant of possible deaths from MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates: 54%-93%) of the mortality decrease was attributable to risk factor reductions: cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical inactivity 5% with adverse trends for diabetes (-5%), and obesity (-4%). Approximately 25% (lower and upper bound estimates: 8%-40%) of the mortality decrease was attributable to treatments in individuals: secondary prevention 8%; heart failure treatments 6%; acute coronary syndrome treatments 5%; revascularisation 3%; hypertension treatments 2%, and statins 0.5%. CONCLUSIONS: Almost three quarters of the large CHD mortality decrease in Iceland between 1981 and 2006 was attributable to reductions in major cardiovascular risk factors in the population. These findings emphasize the value of a comprehensive prevention strategy that promotes tobacco control and a healthier diet to reduce incidence of MI and highlights the potential importance of effective, evidence based medical treatments

Rapid solubility and mineral storage of CO2 in basalt

The long-term security of geologic carbon storage is critical to its success and public acceptance. Much of the security risk associated with geological carbon storage stems from its buoyancy. Gaseous and supercritical CO2 are less dense than formation waters, providing a driving force for it to escape back to the surface. This buoyancy can be eliminated by the dissolution of CO2 into water prior to, or during its injection into the subsurface. The dissolution makes it possible to inject into fractured rocks and further enhance mineral storage of CO2 especially if injected into silicate rocks rich in divalent metal cations such as basalts and ultra-mafic rocks. We have demonstrated the dissolution of CO2 into water during its injection into basalt leading to its geologic solubility storage in less than five minutes and potential geologic mineral storage within few years after injection [1–3]. The storage potential of CO2 within basaltic rocks is enormous. All the carbon released from burning of all fossil fuel on Earth, 5000 GtC, can theoretically be stored in basaltic rocks [4]

Target strength of skipjack tuna (Katsuwanus pelamis) associated with fish aggregating devices (FADs)

[EN] This paper presents measures of target strength (TS; dB re 1 m(2)) and models of TS vs. fork length (L; cm), i.e. TS = 20log(L) + b(20), for skip-jack tuna associated with fish aggregating devices (FADs) in the Central Pacific Ocean. Measurements were made using 38-, 120-, and 200-kHz split-beam echosounders on a purse-seine workboat during fishing operations. To mitigate potential bias due to unresolved targets, TS measurements were rejected if they were not simultaneously detected with multiple echosounder frequencies in approximately the same location. The filtered TS and concomitantly sampled L data were used to estimate b(20) = -76, -71, and -70.5 dB for 38, 120, and 200 kHz, respectively, using the method of least squares. For comparison, quasi-independent estimates of TS and b(20) were calculated from acoustic echo-integration and catch data representing entire aggregations around the FADs. The results differed by <= 1 dB for all three frequencies. The sensitivities of these results to variations in fish morphology and behaviour were explored using a simulation of TS for fish without swimbladders. The utility of the results on acoustic properties of skipjack tuna and next research steps to achieve selective fishing at FADs are discussed.We thank the following organizations and people for their support of this work: the governments of Kiribati, Tuvalu, and Tokelau which permitted this research in their EEZs; Albacora for allowing this work aboard F/V ALBATUN TRES; Fishing Master Euken Mujika; the captain and crew; the scientists and divers J. Filmalter and F. Forget are thanked for invaluable insight about fish behaviour, vertical stratification and non-target species composition at FADs; Hector Pena for providing instruction on the sonar setup and analysis; Yolanda Lacalle for the illustration in Figure 2; and Andres Uriarte for advice concerning transmission of statistical errors. The research reported in the present document was funded by the International Seafood Sustainability Foundation (ISSF) and conducted independently by the authors. The report and its results, professional opinions and conclusions are solely the work of the authors. This paper is contribution 843 from AZTI (Marine or Food Research).Boyra, G..; Moreno, G.; Sobradillo, B.; Pérez Arjona, I.; Sancristóbal, I.; Demer, D. (2018). Target strength of skipjack tuna (Katsuwanus pelamis) associated with fish aggregating devices (FADs). ICES Journal of Marine Science. 75(5):1790-1802. https://doi.org/10.1093/icesjms/fsy041S1790180275

Heterologous Expression and Maturation of an NADP-Dependent [NiFe]-Hydrogenase: A Key Enzyme in Biofuel Production

Hydrogen gas is a major biofuel and is metabolized by a wide range of microorganisms. Microbial hydrogen production is catalyzed by hydrogenase, an extremely complex, air-sensitive enzyme that utilizes a binuclear nickel-iron [NiFe] catalytic site. Production and engineering of recombinant [NiFe]-hydrogenases in a genetically-tractable organism, as with metalloprotein complexes in general, has met with limited success due to the elaborate maturation process that is required, primarily in the absence of oxygen, to assemble the catalytic center and functional enzyme. We report here the successful production in Escherichia coli of the recombinant form of a cytoplasmic, NADP-dependent hydrogenase from Pyrococcus furiosus, an anaerobic hyperthermophile. This was achieved using novel expression vectors for the co-expression of thirteen P. furiosus genes (four structural genes encoding the hydrogenase and nine encoding maturation proteins). Remarkably, the native E. coli maturation machinery will also generate a functional hydrogenase when provided with only the genes encoding the hydrogenase subunits and a single protease from P. furiosus. Another novel feature is that their expression was induced by anaerobic conditions, whereby E. coli was grown aerobically and production of recombinant hydrogenase was achieved by simply changing the gas feed from air to an inert gas (N2). The recombinant enzyme was purified and shown to be functionally similar to the native enzyme purified from P. furiosus. The methodology to generate this key hydrogen-producing enzyme has dramatic implications for the production of hydrogen and NADPH as vehicles for energy storage and transport, for engineering hydrogenase to optimize production and catalysis, as well as for the general production of complex, oxygen-sensitive metalloproteins

The chemistry and saturation states of subsurface fluids during the in situ mineralisation of CO2 and H2S at the CarbFix site in SW-Iceland

In situ carbonation of basaltic rocks could provide a long-term carbon storage solution, which is essential for the success and public acceptance of carbon storage. To demonstrate the viability of this carbon storage solution, 175 tonnes (t) of pure CO2 and 73 tonnes (t) of a 75% CO2-24% H2S-1% H2-gas mixture were sequentially injected into basaltic rocks at the CarbFix site at Hellisheidi, SW-Iceland from January to August 2012. This paper reports the chemistry and saturation states with respect to potential secondary minerals of sub-surface fluids sampled prior to, during, and after the injections. All gases were dissolved in water during their injection into permeable basalts located at 500–800 m depth with temperatures ranging from 20 to 50 °C. A pH decrease and dissolved inorganic carbon (DIC) increase was observed in the first monitoring well, HN-04, about two weeks after each injection began. At storage reservoir target depth, this diverted monitoring well is located ∼125 m downstream from the injection well. A significant increase in H2S concentration, however, was not observed after the second injection. Sampled fluids from the HN-04 well show a rapid increase in Ca, Mg, and Fe concentration during the injections with a gradual decline in the following months. Calculations indicate that the sampled fluids are saturated with respect to siderite about four weeks after the injections began, and these fluids attained calcite saturation about three months after each injection. Pyrite is supersaturated prior to and during the mixed gas injection and in the following months. In July 2013, the HN-04 fluid sampling pump broke down due to calcite precipitation, verifying the carbonation of the injected CO2. Mass balance calculations, based on the recovery of non-reactive tracers co-injected into the subsurface together with the acid-gases, confirm that more than 95% of the CO2 injected into the subsurface was mineralised within a year, and essentially all of the injected H2S was mineralised within four months of its injection. These results demonstrate the viability of the in situ mineralisation of these gases in basaltic rocks as a long-term and safe storage solution for CO2 and H2S

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease