A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

Reduction in young male suicide in Scotland

<p>Abstract</p> <p>Background</p> <p>Rates of suicide and undetermined death increased rapidly in Scotland in the 1980's and 1990's. The largest increases were in men, with a marked increase in rates in younger age groups. This was associated with an increase in hanging as a method of suicide. National suicide prevention work has identified young men as a priority group. Routinely collected national information suggested a decrease in suicide rates in younger men at the beginning of the 21^stcentury. This study tested whether this was a significant change in trend, and whether it was associated with any change in hanging rates in young men.</p> <p>Methods</p> <p>Joinpoint regression was used to estimate annual percentage changes in age-specific rates of suicide and undetermined intent death, and to identify times when the trends changed significantly. Rates of deaths by method in 15 – 29 year old males and females were also examined to assess whether there had been any significant changes in method use in this age group.</p> <p>Results</p> <p>There was a 42% reduction in rates in 15 – 29 year old men, from 42.5/100,000 in 2000 to 24.5/100,000 in 2004. A joinpoint analysis confirmed that this was a significant change. There was also a significant change in trend in hanging in men in this age group, with a reduction in rates after 2000. No other male age group showed a significant change in trend over the period 1980 – 2004. There was a smaller reduction in suicide rates in women in the 15 – 29 year old age group, with a reduction in hanging from 2002.</p> <p>Conclusion</p> <p>There has been a reduction in suicide rates in men aged 15 – 29 years, and this is associated with a significant reduction in deaths by hanging in this age group. It is not clear whether this is related to a change in method preference, or an overall reduction in suicidal behaviour, and review of self-harm data will be required to investigate this further.</p

A Genome-Wide Investigation of SNPs and CNVs in Schizophrenia

We report a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenia. We investigated SNPs using 871 patients and 863 controls, following up the top hits in four independent cohorts comprising 1,460 patients and 12,995 controls, all of European origin. We found no genome-wide significant associations, nor could we provide support for any previously reported candidate gene or genome-wide associations. We went on to examine CNVs using a subset of 1,013 cases and 1,084 controls of European ancestry, and a further set of 60 cases and 64 controls of African ancestry. We found that eight cases and zero controls carried deletions greater than 2 Mb, of which two, at 8p22 and 16p13.11-p12.4, are newly reported here. A further evaluation of 1,378 controls identified no deletions greater than 2 Mb, suggesting a high prior probability of disease involvement when such deletions are observed in cases. We also provide further evidence for some smaller, previously reported, schizophrenia-associated CNVs, such as those in NRXN1 and APBA2. We could not provide strong support for the hypothesis that schizophrenia patients have a significantly greater "load" of large (> 100 kb), rare CNVs, nor could we find common CNVs that associate with schizophrenia. Finally, we did not provide support for the suggestion that schizophrenia-associated CNVs may preferentially disrupt genes in neurodevelopmental pathways. Collectively, these analyses provide the first integrated study of SNPs and CNVs in schizophrenia and support the emerging view that rare deleterious variants may be more important in schizophrenia predisposition than common polymorphisms. While our analyses do not suggest that implicated CNVs impinge on particular key pathways, we do support the contribution of specific genomic regions in schizophrenia, presumably due to recurrent mutation. On balance, these data suggest that very few schizophrenia patients share identical genomic causation, potentially complicating efforts to personalize treatment regimens