Macronutrient and carbon supply, uptake and cycling across the Antarctic Peninsi shelf during summer

The West Antarctic Peninsula shelf is a region of high seasonal primary production which supports a large and productive food web, where macronutrients and inorganic carbon are sourced primarily from intrusions of warm saline Circumpolar Deep Water. We examined the cross-shelf modification of this water mass during mid-summer 2015 to understand the supply of nutrients and carbon to the productive surface ocean, and their subsequent uptake and cycling. We show that nitrate, phosphate, silicic acid and inorganic carbon are progressively enriched in subsurface waters across the shelf, contrary to cross-shelf reductions in heat, salinity and density. We use nutrient stoichiometric and isotopic approaches to invoke remineralization of organic matter, including nitrification below the euphotic surface layer, and dissolution of biogenic silica in deeper waters and potentially shelf sediment porewaters, as the primary drivers of cross-shelf enrichments. Regenerated nitrate and phosphate account for a significant proportion of the total pools of these nutrients in the upper ocean, with implications for the seasonal carbon sink. Understanding nutrient and carbon dynamics in this region now will inform predictions of future biogeochemical changes in the context of substantial variability and ongoing changes in the physical environment

Autoantibodies to truncated GAD(96-585) antigen stratify risk of early insulin requirement in adult-onset diabetes

We investigated whether characterisation of full-length (f-)GADA responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA positive participants diagnosed with type 2 diabetes, we assessed associations of truncated (t-)GADA positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA positive without early insulin in comparison to f-GADA positive type 2 diabetes requiring insulin within 5 years, and type 1 diabetes (75% vs. 91% and 95% respectively, p<0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher type 1 diabetes genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, p=0.003), lower C-peptide (1156 pmol/L vs. 4289 pmol/L, p=1x10-7), and increased IA-2A positivity (23% vs. 6%, p=0.03). In survival analysis, t-GADA positivity was associated with early insulin requirement compared with those only positive for f-GADA, independently from age of diagnosis, f-GADA titre and duration of diabetes [adjusted HR 5.7 (95% CI 1.4, 23.5), p=0.017]. The testing of t-GADA in f-GADA positive individuals with type 2 diabetes identifies those who have genetic and clinical characteristics comparable to type 1 diabetes and stratifies those at higher risk of early insulin requirement

Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas

Colorectal tumours from MYH polyposis patients display an excess of somatic G : C right arrow T : A transversions in the adenomatous polyposis coli gene. Here, we identify k-ras mutations in nine out of 54 (16.7%) MYH polyposis tumours. Their presence was associated with increased dysplasia and tubulovillous morphology (P=0.005). G : C right arrow T : A transversions in k-ras were significantly more frequent in MYH polyposis adenomas than in sporadic or familial adenomatous polyposis-associated tumours (Pless than or equal to0.002), and all resulted in a glycine-to-cysteine substitution at codon 12

Higher Serum Immunoglobulin G3 Levels May Predict the Development of Multiple Sclerosis in Individuals With Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1-4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein-Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of "upstream" to "downstream" IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS.ST, AJ, and MF-P are recipients of the Multiple Sclerosis Society of Western Australia (MSWA) Postdoctoral Research Fellowship. RL is a recipient of a National Health and Medical Research Council Senior Research Fellowship. This work is funded by a National Health and Medical Research Council Project Grant (ID 1067209)

The association between air pollution and type 2 diabetes in a large cross-sectional study in Leicester: The CHAMPIONS Study

Background: Observational evidence suggests there is an association between air pollution and type 2 diabetes; however, there is high risk of bias. Objective: To investigate the association between air pollution and type 2 diabetes, while reducing bias due to exposure assessment, outcome assessment, and confounder assessment. Methods: Data were collected from 10,443 participants in three diabetes screening studies in Leicestershire, UK. Exposure assessment included standard, prevailing estimates of outdoor nitrogen dioxide and particulate matter concentrations in a 1 × 1 km area at the participant's home postcode. Three-year exposure was investigated in the primary analysis and one-year exposure in a sensitivity analysis. Outcome assessment included the oral glucose tolerance test for type 2 diabetes. Confounder assessment included demographic factors (age, sex, ethnicity, smoking, area social deprivation, urban or rural location), lifestyle factors (body mass index and physical activity), and neighbourhood green space. Results: Nitrogen dioxide and particulate matter concentrations were associated with type 2 diabetes in unadjusted models. There was no statistically significant association between nitrogen dioxide concentration and type 2 diabetes after adjustment for demographic factors (odds: 1.08; 95% CI: 0.91, 1.29). The odds of type 2 diabetes was 1.10 (95% CI: 0.92, 1.32) after further adjustment for lifestyle factors and 0.91 (95% CI: 0.72, 1.16) after yet further adjustment for neighbourhood green space. The associations between particulate matter concentrations and type 2 diabetes were also explained away by demographic factors. There was no evidence of exposure definition bias. Conclusions: Demographic factors seemed to explain the association between air pollution and type 2 diabetes in this cross-sectional study. High-quality longitudinal studies are needed to improve our understanding of the association

Impact of sea-ice melt on dimethyl sulfide (sulfoniopropionate) inventories in surface waters of Marguerite Bay, West Antarctic Peninsula

The Southern Ocean is a hotspot of the climate-relevant organic sulfur compound dimethyl sulfide (DMS). Spatial and temporal variability in DMS concentration is higher than in any other oceanic region, especially in the marginal ice zone. During a one-week expedition across the continental shelf of the West Antarctic Peninsula (WAP), from the shelf break into Marguerite Bay, in January 2015, spatial heterogeneity of DMS and its precursor dimethyl sulfoniopropionate (DMSP) was studied and linked with environmental conditions, including sea-ice melt events. Concentrations of sulfur compounds, particulate organic carbon (POC) and chlorophyll a in the surface waters varied by a factor of 5–6 over the entire transect. DMS and DMSP concentrations were an order of magnitude higher than currently inferred in climatologies for the WAP region. Particulate DMSP concentrations were correlated most strongly with POC and the abundance of haptophyte algae within the phytoplankton community, which, in turn, was linked with sea-ice melt. The strong sea-ice signal in the distribution of DMS(P) implies that DMS(P) production is likely to decrease with ongoing reductions in sea-ice cover along the WAP. This has implications for feedback processes on the region's climate system

Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment

Child Mortality in Rural Malawi: HIV Closes the Survival Gap between the Socio-Economic Strata

BACKGROUND: As HIV-related deaths increase in a population the usual association between low socioeconomic status and child mortality may change, particularly as death rates from other causes decline. METHODS/PRINCIPAL FINDINGS: As part of a demographic surveillance system in northern Malawi in 2002-6, covering a population of 32,000, information was collected on socio-economic status of the households. Deaths were classified as HIV/AIDS-related or not by verbal autopsy. Poisson regression models were used to assess the association of socio-economic indicators with all-cause mortality, AIDS-mortality and non-AIDS mortality among children. There were 195 deaths in infants, 109 in children aged 1-4 years, and 38 in children aged 5-15. All-cause child mortality in infants and 1-4 year olds was similar in households with higher and lower socio-economic status. In infants 13% of deaths were attributed to AIDS, and there were no clear trends with socio-economic status for AIDS or non-AIDS causes. For 1-4 year olds 27% of deaths were attributed to AIDS. AIDS mortality was higher among those with better built houses, and lowest in those with income from farming and fishing, whereas non-AIDS mortality was higher in those with worse built houses, lowest in those with income from employment, and decreased with increasing household assets. CONCLUSIONS/SIGNIFICANCE: In this population, since HIV infection among adults was initially more common among the less poor, childhood mortality patterns have changed. The usual gap in survival between the poor and the less poor has been lost, but because the less poor have been disproportionately affected by HIV, rather than because of relative improvement in the survival of the poorest