An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A?C (1?3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 1?7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey's method employing the new reagent l-Na-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4? T cells decreased T cell secretion of IFN-?, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC50 values 11.8 and 21.0 µM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-? or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.
An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A?C (1?3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 1?7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey's method employing the new reagent l-Na-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4? T cells decreased T cell secretion of IFN-?, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC50 values 11.8 and 21.0 µM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-? or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.
A total of 1075 Russians from the Russian part of Karelia were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next generation sequencing methods. The haplotypic and allelic profiles as well as Hardy-Weinberg proportions of this population sample were evaluated. As the most frequent 6-locus haplotype, A*03:01?g?~?B*07:02?g?~?C*07:02?g?~?DRB1*15:01?g?~?DQB1*06:02?g?~?DPB1*04:01?g was identified with an estimated frequency of 3.5%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name "Russia Karelia" and the identifier AFN3430.
International reports have suggested that food allergies and food-induced anaphylaxis have increased in children. We investigated the incidence of emergency food reactions over a 10-year period.
This study retrospectively reviewed the medical records of children presenting to Umeå University hospital, Sweden, with an emergency food reaction from January 1, 2006 to December 31, 2015. Cases were identified using discharge codes for allergies and anaphylaxis. Anaphylaxis cases were included if they fulfilled the international criteria.
We found emergency food allergy reactions in 519 children (58% boys) from 2006-2015 at a median age of 1.3 years. One-third were hospitalised (32%) including 71/99 cases of anaphylaxis. Milk and eggs were the most commonly identified triggers. Emergency reactions to eggs increased during the study period with a Spearman rank correlation coefficient of 0.770 (p
Studies from several countries suggest that erecting fences on bridges more commonly used for suicide by jumping may be an effective way of reducing the risk of suicide by jumping from these bridges. Distribution of suicides by jumping off bridges has not yet been studied on a national level in any country. This study included all suicides by jumping from high places registered in the Norwegian Cause of Death Registry (COD) in the period 1999-2010 (n = 319). Combining data from the COD registry and information from police records, 71 cases of suicide by jumping off a bridge were identified involving 36 bridges. This form of suicide constituted approximately 1% of all suicides in Norway in the period 1999-2010. Almost half of these suicides were registered at only 6 bridges. Three Norwegian bridges were secured during the observation period of this study. Two bridges had barriers installed on the full length of the bridge with 11 suicides registered before barriers were installed, and none after. On the 1 bridge that was only partially secured, no change in numbers of suicides was observed after barriers were installed. One-third of jumps from bridges occurred over land. We found that although suicide by jumping off bridges was a relatively rare event, there is a potential for saving lives by installing physical barriers on bridges that are more commonly used for suicide by jumping.
Climate change effects on marine ecosystems include impacts on primary production, ocean temperature, species distributions and abundance at local to global scales. These changes will significantly alter marine ecosystem structure and function with associated socio-economic impacts on ecosystem services, marine fisheries, and fishery-dependent societies. Yet how these changes may play out among ocean basins over the 21st century remains unclear, with most projections coming from single ecosystem models that do not adequately capture the range of model uncertainty. We address this by using six marine ecosystem models within the Fisheries and Marine Ecosystem Model Intercomparison Project (Fish-MIP) to analyze responses of marine animal biomass in all major ocean basins to contrasting climate change scenarios. Under a high emissions scenario (RCP8.5), total marine animal biomass declined by an ensemble mean of 15-30% (±12-17%) in the North and South Atlantic and Pacific, and the Indian Ocean by 2100, whereas polar ocean basins experienced a 20-80% (±35-200%) increase. Uncertainty and model disagreement were greatest in the Arctic and smallest in the South Pacific Ocean. Projected changes were reduced under a low (RCP2.6) emissions scenario. Under RCP2.6 and RCP8.5, biomass projections were highly correlated with changes in net primary production and negatively correlated with projected sea surface temperature increases across all ocean basins except the polar oceans. Ecosystem structure was projected to shift as animal biomass concentrated in different size-classes across ocean basins and emissions scenarios. We highlight that climate change mitigation measures could moderate the impacts on marine animal biomass by reducing biomass declines in the Pacific, Atlantic, and Indian Ocean basins. The range of individual model projections emphasizes the importance of using an ensemble approach in assessing uncertainty of future change. This article is protected by copyright. All rights reserved.
Permafrost carbon feedback (PCF) modeling has focused on gradual thaw of near-surface permafrost leading to enhanced carbon dioxide and methane emissions that accelerate global climate warming. These state-of-the-art land models have yet to incorporate deeper, abrupt thaw in the PCF. Here we use model data, supported by field observations, radiocarbon dating, and remote sensing, to show that methane and carbon dioxide emissions from abrupt thaw beneath thermokarst lakes will more than double radiative forcing from circumpolar permafrost-soil carbon fluxes this century. Abrupt thaw lake emissions are similar under moderate and high representative concentration pathways (RCP4.5 and RCP8.5), but their relative contribution to the PCF is much larger under the moderate warming scenario. Abrupt thaw accelerates mobilization of deeply frozen, ancient carbon, increasing 14C-depleted permafrost soil carbon emissions by ~125-190% compared to gradual thaw alone. These findings demonstrate the need to incorporate abrupt thaw processes in earth system models for more comprehensive projection of the PCF this century.
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Cites: Philos Trans A Math Phys Eng Sci. 2015 Nov 13;373(2054):null PMID 26438276
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Cites: Nature. 2018 Jan 31;554(7690):92-96 PMID 29388952
Cites: Nat Commun. 2016 Oct 11;7:13043 PMID 27725633
Permafrost carbon feedback (PCF) modeling has focused on gradual thaw of near-surface permafrost leading to enhanced carbon dioxide and methane emissions that accelerate global climate warming. These state-of-the-art land models have yet to incorporate deeper, abrupt thaw in the PCF. Here we use model data, supported by field observations, radiocarbon dating, and remote sensing, to show that methane and carbon dioxide emissions from abrupt thaw beneath thermokarst lakes will more than double radiative forcing from circumpolar permafrost-soil carbon fluxes this century. Abrupt thaw lake emissions are similar under moderate and high representative concentration pathways (RCP4.5 and RCP8.5), but their relative contribution to the PCF is much larger under the moderate warming scenario. Abrupt thaw accelerates mobilization of deeply frozen, ancient carbon, increasing 14C-depleted permafrost soil carbon emissions by ~125-190% compared to gradual thaw alone. These findings demonstrate the need to incorporate abrupt thaw processes in earth system models for more comprehensive projection of the PCF this century.
