Exome sequencing of Finnish isolates enhances rare-variant association power.

Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power

Horizontal Gene Transfer of a ColV Plasmid Has Resulted in a Dominant Avian Clonal Type of Salmonella enterica Serovar Kentucky

Salmonella enterica continues to be a significant cause of foodborne gastrointestinal illness in humans. A wide variety of Salmonella serovars have been isolated from production birds and from retail poultry meat. Recently, though, S. enterica subsp. enterica serovar Kentucky has emerged as one of the prominent Salmonella serovars isolated from broiler chickens. Recent work suggests that its emergence apparently coincides with its acquisition of a ColV virulence plasmid. In the present study, we examined 902 Salmonella isolates belonging to 59 different serovars for the presence of this plasmid. Of the serovars examined, the ColV plasmid was found only among isolates belonging to the serovars Kentucky (72.9%), Typhimurium (15.0%) and Heidelberg (1.7%). We demonstrated that a single PFGE clonal type of S. Kentucky harbors this plasmid, and acquisition of this plasmid by S. Kentucky significantly increased its ability to colonize the chicken cecum and cause extraintestinal disease. Comparison of the completed sequences of three ColV plasmids from S. Kentucky isolated from different geographical locales, timepoints and sources revealed a nearly identical genetic structure with few single nucleotide changes or insertions/deletions. Overall, it appears that the ColV plasmid was recently acquired by a single clonal type S. Kentucky and confers to its host enhanced colonization and fitness capabilities. Thus, the potential for horizontal gene transfer of virulence and fitness factors to Salmonella from other enteric bacteria exists in poultry, representing a potential human health hazard

Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands: the MOYA and ZWAMPS flights

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ13CCH4 isotopic signatures were in the range −55 to −49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely −60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ13CCH4 signatures were measured over the Amazonian wetlands of NE Bolivia (around −59‰) and the overall δ13CCH4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was −59 ± 2‰. These results were more negative than expected. For African cattle, δ13CCH4 values were around −60 to −50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ13CCH4 values were around −28‰. By contrast, African C4 tropical grass fire δ13CCH4 values were −16 to −12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ13CCH4 around −37 to −36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ13CCH4 values predicted by global atmospheric models are highly sensitive to the δ13CCH4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.Natural Environment Research Council (NERC): NE/S00159X/1; NE/N016238/1; NE/P019641/

Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands: the MOYA and ZWAMPS flights.

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ13CCH4 isotopic signatures were in the range -55 to -49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely -60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ13CCH4 signatures were measured over the Amazonian wetlands of NE Bolivia (around -59‰) and the overall δ13CCH4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was -59 ± 2‰. These results were more negative than expected. For African cattle, δ13CCH4 values were around -60 to -50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ13CCH4 values were around -28‰. By contrast, African C4 tropical grass fire δ13CCH4 values were -16 to -12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ13CCH4 around -37 to -36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ13CCH4 values predicted by global atmospheric models are highly sensitive to the δ13CCH4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'

Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands : The MOYA and ZWAMPS flights

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ 13 C CH 4 isotopic signatures were in the range -55 to -49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely -60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ 13 C CH 4 signatures were measured over the Amazonian wetlands of NE Bolivia (around -59‰) and the overall δ 13 C CH 4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was -59 ± 2‰. These results were more negative than expected. For African cattle, δ 13 C CH 4 values were around -60 to -50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3: C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ 13 C CH 4 values were around -28‰. By contrast, African C4 tropical grass fire δ 13 C CH 4 values were -16 to -12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ 13 C CH 4 around -37 to -36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ 13 C CH 4 values predicted by global atmospheric models are highly sensitive to the δ 13 C CH 4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'

Global Molecular Epidemiology of the O15:K52:H1 Extraintestinal Pathogenic Escherichia coli Clonal Group: Evidence of Distribution beyond Europe

Escherichia coli O15:K52:H1 is a significant extraintestinal pathogen in Europe (G. Prats et al., J. Clin. Microbiol. 38:201-209, 2000). To search for evidence of this clonal group outside of Europe, 75 non-European E. coli isolates of serogroup O15 were compared with five members of the O15:K52:H1 clonal group from Barcelona, Spain, according to genomic background, virulence genotypes, and antimicrobial resistance profiles. Amplification phylotyping showed that 16 (21%) of the 75 non-European O15 isolates corresponded with the O15:K52:H1 clonal group. The 16 non-European O15:K52:H1 clonal group members represented diverse geographic locales. They were isolated almost exclusively from humans with extraintestinal infections and accounted for 50% of all O15 isolates from five human clinical collections studied. Most non-European clonal group members exhibited a consensus virulence factor profile that included the F16 or F7-2 papA alleles (P fimbrial structural subunit), papG allele II (P fimbrial adhesin), iha (putative adhesin siderophore), and iutA (aerobactin receptor). This resembles the virulence profiles of (i) European representatives of the O15:K52:H1 clonal group and (ii) phylogenetically related “clonal group A,” a recently recognized significant contributor to trimethoprim-sulfamethoxazole resistance in the United States (A. R. Manges et al., N. Engl. J. Med. 345:1007-1013, 2001). Antimicrobial resistance profiles were variable, and resistance was inconsistently transferred by conjugation. These findings indicate that the O15:K52:H1 clonal group is broadly distributed beyond Europe, exhibits previously unrecognized phenotypic and genotypic diversity, and contributes significantly to extraintestinal infections in humans

Oxidative stress in pancreatic alpha and beta cells as a selection criterion for biocompatible biomaterials

The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets