MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction

Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a -168A --> G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-gamma. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components.     

Changes in the distribution of marital age differences in England and Wales, 1963 to 1998

Assumptions about the 'typical' age gap between spouses underlie much social policy (e.g. the five-year difference in men's and women's state pension ages). In order to test the basis for these assumptions, detailed marriage registration statistics were obtained for 1963 and 1998, for England and Wales. Age differences between spouses were calculated and analysed by year, age at marriage and previous marital status. The median age gap hardly changed between 1963 and 1998 but this concealed considerable increase in the proportion of marriages where the man was younger than the woman or--to a lesser extent--where the man was six or more years older.     

Identification of ALK as a major familial neuroblastoma predisposition gene

Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.     

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).     

Perception and description of New World non-human primates in the travel literature of the fifteenth and sixteenth centuries: a critical review

The current work presents the results of a review of most of the European diaries and travel chronicles containing reports of New World non-human primates dating from the discovery of America in 1492 until the end of the sixteenth century. We report the integral texts translated into English of these literary sources, giving a critical interpretation from a historical and scientific point of view. We note the ways these primates were perceived and described, with attention to the most important characteristics that were highlighted by the first explorers. Ethnotaxonomy and vernacular names used to designate non-human primates are also provided. This new body of knowledge, based largely on empirical reports full of details and first-hand observations, emerged as the first nucleus in the natural history of Neotropical Primates.     

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).     

Arctic warming aloft is data set dependent

Arctic sea ice and snow on land have retreated polewards at an alarming pace in the past few decades. Such retreat locally amplifies surface warming through a positive feedback, which causes the Arctic surface to warm faster than the rest of the globe. In contrast, ice and snow retreat causes little warming in the atmosphere above when the stable winter atmosphere inhibits vertical heat exchange. We therefore find surprising the recent report by Graversen et al. in which they claim that recent Arctic atmospheric warming extends far deeper into the atmosphere than expected, and can even exceed the surface warming during the polar night. Using a different data set, we show that there is much less warming aloft in winter, consistent with the recent retreat of ice and snow, as well as recent changes in atmospheric heat transport.     

New proposals for the quantification of qualitative survey data

In this paper we propose and evaluate two new methods for the quantification of business surveys concerning the qualitative assessment of the state of the economy. The first is a nonparametric method based on the spectral envelope, originally proposed by Stoffer, Tyler and McDougall (Spectral analysis for categorical time series: scaling and the spectral envelope, Biometrika 80 : 611–622) to the multivariate time series of the counts in each response category. Secondly, we fit by maximum likelihood a cumulative logit unobserved components models featuring a common cycle. The conditional mean of the cycle, which can be evaluated by importance sampling, offers the required quantification. We assess the validity of the two methods by comparing the results with a standard quantification based on the balance of opinions and with a quantitative economic indicator. Copyright ? 2010 John Wiley & Sons, Ltd.