Effect of natural iron fertilization on carbon sequestration in the Southern Ocean

The availability of iron limits primary productivity and the associated uptake of carbon over large areas of the ocean. Iron thus plays an important role in the carbon cycle, and changes in its supply to the surface ocean may have had a significant effect on atmospheric carbon dioxide concentrations over glacial-interglacial cycles. To date, the role of iron in carbon cycling has largely been assessed using short-term iron-addition experiments. It is difficult, however, to reliably assess the magnitude of carbon export to the ocean interior using such methods, and the short observational periods preclude extrapolation of the results to longer timescales. Here we report observations of a phytoplankton bloom induced by natural iron fertilization--an approach that offers the opportunity to overcome some of the limitations of short-term experiments. We found that a large phytoplankton bloom over the Kerguelen plateau in the Southern Ocean was sustained by the supply of iron and major nutrients to surface waters from iron-rich deep water below. The efficiency of fertilization, defined as the ratio of the carbon export to the amount of iron supplied, was at least ten times higher than previous estimates from short-term blooms induced by iron-addition experiments. This result sheds new light on the effect of long-term fertilization by iron and macronutrients on carbon sequestration, suggesting that changes in iron supply from below--as invoked in some palaeoclimatic and future climate change scenarios--may have a more significant effect on atmospheric carbon dioxide concentrations than previously thought.     

Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).     

HLA-G in organ transplantation: towards clinical applications

HLA-G plays a particular role during pregnancy in which its expression at the feto–maternal barrier participates into the tolerance of the allogenic foetus. HLA-G has also been demonstrated to be expressed in some transplanted patients, suggesting that it regulates the allogenic response. In vitro data indicate that HLA-G modulates NK cells, T cells, and DC maturation through its interactions with various inhibitory receptors. In this paper, we will review the data reporting the HLA-G involvement of HLA-G in human organ transplantation, then factors that can modulate HLA-G, and finally the use of HLA-G as a therapeutic tool in organ transplantation.     

Toward interoperable bioscience data

To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.     

SUMO1-dependent modulation of SERCA2a in heart failure

The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical ATPase responsible for Ca(2+) re-uptake during excitation-contraction coupling. Impaired Ca(2+) uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO1 restitution by adeno-associated-virus-mediated gene delivery maintained the protein abundance of SERCA2a and markedly improved cardiac function in mice with heart failure. This effect was comparable to SERCA2A gene delivery. Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay. Transgene-mediated SUMO1 overexpression rescued cardiac dysfunction induced by pressure overload concomitantly with increased SERCA2a function. By contrast, downregulation of SUMO1 using small hairpin RNA (shRNA) accelerated pressure-overload-induced deterioration of cardiac function and was accompanied by decreased SERCA2a function. However, knockdown of SERCA2a resulted in severe contractile dysfunction both in vitro and in vivo, which was not rescued by overexpression of SUMO1. Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure.