Transient climate simulations with the HadGEM1 climate model: Causes of past warming and future climate change

The ability of climate models to simulate large-scale temperature changes during the twentieth century when they include both anthropogenic and natural forcings and their inability to account for warming over the last 50 yr when they exclude increasing greenhouse gas concentrations has been used as evidence for an anthropogenic influence on global warming. One criticism of the models used in many of these studies is that they exclude some forcings of potential importance, notably from fossil fuel black carbon, biomass smoke, and land use changes. Herein transient simulations with a new model, the Hadley Centre Global Environmental Model version 1 (HadGEM1), are described, which include these forcings in addition to other anthropogenic and natural forcings, and a fully interactive treatment of atmospheric sulfur and its effects on clouds. These new simulations support previous work by showing that there was a significant anthropogenic influence on near-surface temperature change over the last century. They demonstrate that black carbon and land use changes are relatively unimportant for explaining global mean near-surface temperature changes. The pattern of warming in the troposphere and cooling in the stratosphere that has been observed in radiosonde data since 1958 can only be reproduced when the model includes anthropogenic forcings

Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.

BACKGROUND: The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1). RESULTS: We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. CONCLUSION: We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Analysis of polymorphisms in 16 genes in type 1 diabetes that have been associated with other immune-mediated diseases.

BACKGROUND: The identification of the HLA class II, insulin (INS), CTLA-4 and PTPN22 genes as determinants of type 1 diabetes (T1D) susceptibility indicates that fine tuning of the immune system is centrally involved in disease development. Some genes have been shown to affect several immune-mediated diseases. Therefore, we tested the hypothesis that alleles of susceptibility genes previously associated with other immune-mediated diseases might perturb immune homeostasis, and hence also associate with predisposition to T1D. METHODS: We resequenced and genotyped tag single nucleotide polymorphisms (SNPs) from two genes, CRP and FCER1B, and genotyped 27 disease-associated polymorphisms from thirteen gene regions, namely FCRL3, CFH, SLC9A3R1, PADI4, RUNX1, SPINK5, IL1RN, IL1RA, CARD15, IBD5-locus (including SLC22A4), LAG3, ADAM33 and NFKB1. These genes have been associated previously with susceptibility to a range of immune-mediated diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Graves' disease (GD), psoriasis, psoriatic arthritis (PA), atopy, asthma, Crohn disease and multiple sclerosis (MS). Our T1D collections are divided into three sample subsets, consisting of set 1 families (up to 754 families), set 2 families (up to 743 families), and a case-control collection (ranging from 1,500 to 4,400 cases and 1,500 to 4,600 controls). Each SNP was genotyped in one or more of these subsets. Our study typically had approximately 80% statistical power for a minor allele frequency (MAF) >5% and odds ratios (OR) of 1.5 with the type 1 error rate, alpha = 0.05. RESULTS: We found no evidence of association with T1D at most of the loci studied 0.02 <P < 1.0. Only a SNP in ADAM33, rs2787094, was any evidence of association obtained, P = 0.0004 in set 1 families (relative risk (RR) = 0.78), but further support was not observed in the 4,326 cases and 4,610 controls, P = 0.57 (OR = 1.02). CONCLUSION: Polymorphisms in a variety of genes previously associated with immune-mediated disease susceptibility and/or having effects on gene function and the immune system, are unlikely to be affecting T1D susceptibility in a major way, even though some of the genes tested encode proteins of immune pathways that are believed to be central to the development of T1D. We cannot, however, rule out effect sizes smaller than OR 1.5

Discovery, linkage disequilibrium and association analyses of polymorphisms of the immune complement inhibitor, decay-accelerating factor gene (DAF/CD55) in type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells. Decay accelerating factor (DAF, CD55), a glycosylphosphatidylinositol-anchored membrane protein, is a candidate for autoimmune disease susceptibility based on its role in restricting complement activation and evidence that DAF expression modulates the phenotype of mice models for autoimmune disease. In this study, we adopt a linkage disequilibrium (LD) mapping approach to test for an association between the DAF gene and T1D. RESULTS: Initially, we used HapMap II genotype data to examine LD across the DAF region. Additional resequencing was required, identifying 16 novel polymorphisms. Combining both datasets, a LD mapping approach was adopted to test for association with T1D. Seven tag SNPs were selected and genotyped in case-control (3,523 cases and 3,817 controls) and family (725 families) collections. CONCLUSION: We obtained no evidence of association between T1D and the DAF region in two independent collections. In addition, we assessed the impact of using only HapMap II genotypes for the selection of tag SNPs and, based on this study, found that HapMap II genotypes may require additional SNP discovery for comprehensive LD mapping of some genes in common disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

An objective tropical Atlantic sea surface temperature gradient index for studies of south Amazon dry-season climate variability and change

Future changes in meridional sea surface temperature (SST) gradients in the tropical Atlantic could influence Amazon dry-season precipitation by shifting the patterns of moisture convergence and vertical motion. Unlike for the El Niño-Southern Oscillation, there are no standard indices for quantifying this gradient. Here we describe a method for identifying the SST gradient that is most closely associated with June–August precipitation over the south Amazon. We use an ensemble of atmospheric general circulation model (AGCM) integrations forced by observed SST from 1949 to 2005. A large number of tropical Atlantic SST gradient indices are generated randomly and temporal correlations are examined between these indices and June–August precipitation averaged over the Amazon Basin south of the equator. The indices correlating most strongly with June–August southern Amazon precipitation form a cluster of near-meridional orientation centred near the equator. The location of the southern component of the gradient is particularly well defined in a region off the Brazilian tropical coast, consistent with known physical mechanisms. The chosen index appears to capture much of the Atlantic SST influence on simulated southern Amazon dry-season precipitation, and is significantly correlated with observed southern Amazon precipitation

IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production

Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report “allelic heterogeneity” at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels

Increased importance of methane reduction for a 1.5 degree target

To understand the importance of methane on the levels of carbon emission reductions required to achieve temperature goals, a processed-based approach is necessary rather than reliance on the Transient Climate Response to Emissions. We show that plausible levels of methane (CH4) mitigation can make a substantial difference to the feasibility of achieving the Paris climate targets through increasing the allowable carbon emissions. This benefit is enhanced by the indirect effects of CH4 on ozone (O3). Here the differing effects of CH4 and CO2 on land carbon storage, including the effects of surface O3, lead to an additional increase in the allowable carbon emissions with CH4 mitigation. We find a simple robust relationship between the change in the 2100 CH4 concentration and the extra allowable cumulative carbon emissions between now and 2100 (0.27 ± 0.05 GtC per ppb CH4). This relationship is independent of modelled climate sensitivity and precise temperature target, although later mitigation of CH4 reduces its value and thus methane reduction effectiveness. Up to 12% of this increase in allowable emissions is due to the effect of surface ozone. We conclude early mitigation of CH4 emissions would significantly increase the feasibility of stabilising global warming below 1.5C, alongside having co-benefits for human and ecosystem health

Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.

BACKGROUND: One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3 (orthologous to Vav3 in Idd18). RESULTS: Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls. CONCLUSION: None of the candidate regions showed evidence of association with type 1 diabetes (P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Three red suns in the sky: A transiting, terrestrial planet in a triple M-dwarf system at 6.9 pc

We present the discovery from Transiting Exoplanet Survey Satellite (TESS) data of LTT 1445Ab. At a distance of 6.9 pc, it is the second nearest transiting exoplanet system found to date, and the closest one known for which the primary is an M dwarf. The host stellar system consists of three mid-to-late M dwarfs in a hierarchical configuration, which are blended in one TESS pixel. We use MEarth data and results from the Science Processing Operations Center data validation report to determine that the planet transits the primary star in the system. The planet has a radius of ${1.38}_{-0.12}^{+0.13}$ ${R}_{\oplus }$, an orbital period of ${5.35882}_{-0.00031}^{+0.00030}$ days, and an equilibrium temperature of ${433}_{-27}^{+28}$ K. With radial velocities from the High Accuracy Radial Velocity Planet Searcher, we place a 3σ upper mass limit of 8.4 ${M}_{\oplus }$ on the planet. LTT 1445Ab provides one of the best opportunities to date for the spectroscopic study of the atmosphere of a terrestrial world. We also present a detailed characterization of the host stellar system. We use high-resolution spectroscopy and imaging to rule out the presence of any other close stellar or brown dwarf companions. Nineteen years of photometric monitoring of A and BC indicate a moderate amount of variability, in agreement with that observed in the TESS light-curve data. We derive a preliminary astrometric orbit for the BC pair that reveals an edge-on and eccentric configuration. The presence of a transiting planet in this system hints that the entire system may be co-planar, implying that the system may have formed from the early fragmentation of an individual protostellar core.Accepted manuscrip