Common variants in WFS1 confer risk of type 2 diabetes

We studied genes involved in pancreatic beta cell function and survival, identifying associations between SNPs in WFS1 and diabetes risk in UK populations that we replicated in an Ashkenazi population and in additional UK studies. In a pooled analysis comprising 9,533 cases and 11,389 controls, SNPs in WFS1 were strongly associated with diabetes risk. Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes.     

A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia

We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 x 10(-10)), 2q37.1 (rs13397985, SP140; P = 5.40 x 10(-10)), 6p25.3 (rs872071, IRF4; P = 1.91 x 10(-20)), 11q24.1 (rs735665; P = 3.78 x 10(-12)), 15q23 (rs7176508; P = 4.54 x 10(-12)) and 19q13.32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.     

Translation factors promote the formation of two states of the closed-loop mRNP

Efficient translation initiation and optimal stability of most eukaryotic messenger RNAs depends on the formation of a closed-loop structure and the resulting synergistic interplay between the 5' m(7)G cap and the 3' poly(A) tail. Evidence of eIF4G and Pab1 interaction supports the notion of a closed-loop mRNP, but the mechanistic events that lead to its formation and maintenance are still unknown. Here we use toeprinting and polysome profiling assays to delineate ribosome positioning at initiator AUG codons and ribosome-mRNA association, respectively, and find that two distinct stable (resistant to cap analogue) closed-loop structures are formed during initiation in yeast cell-free extracts. The integrity of both forms requires the mRNA cap and poly(A) tail, as well as eIF4E, eIF4G, Pab1 and eIF3, and is dependent on the length of both the mRNA and the poly(A) tail. Formation of the first structure requires the 48S ribosomal complex, whereas the second requires an 80S ribosome and the termination factors eRF3/Sup35 and eRF1/Sup45. The involvement of the termination factors is independent of a termination event.     

Long‐Run and Cyclical Dynamics in the US Stock Market

This paper uses fractional integration to examine the long‐run dynamics and cyclical structure of US inflation, real risk‐free rate, real stock returns, equity premium and price/dividend ratio, annually from 1871 to 2000. It implements a procedure which allows consideration of unit roots with possibly fractional orders of integration both at zero (long‐run) and cyclical frequencies. When focusing exclusively on the former, the estimated order of integration varies considerably, and non‐stationarity is found only for the price/dividend ratio. When the cyclical component is also taken into account, the series appear to be stationary but to exhibit long memory with respect to both components in almost all cases. The exception is the price/dividend ratio, whose order of integration is higher than 0.5 but smaller than 1 for the long‐run frequency, and is between 0 and 0.5 for the cyclical component. Also, mean reversion occurs in all cases. Finally, six different criteria are applied to compare the forecasting performance of the fractional (at both zero and cyclical frequencies) models with others based on fractional and integer differentiation only at the zero frequency. The results, based on a 15‐year horizon, show that the former outperforms the others in a number of cases. Copyright © 2013 John Wiley & Sons, Ltd.     

Evidence for only minor contributions from bacteria to sedimentary organic carbon

Because their molecular signatures are often prominent in extracts of sediments, bacteria are thought to be important contributors to petroleum source beds. It has been shown recently, however, that abundances of biomarkers do not always reflect relative contributions to sedimentary organic carbon (Corg). The contribution of photosynthetic green sulphur bacteria to sediments can be assessed effectively because the diagenetic products of distinctive carotenoids from these organisms occur widely and their biomass is isotopically labelled, being enriched in 13C. We show here that, although sediments and oils from the Western Canada and Williston basins contain prominent biomarkers of photosynthetic bacteria, the absence of 13C enrichment in the total Corg requires that the bacterial contribution is in fact minimal. Although the importance of bacterial reworking of sedimentary debris cannot be doubted, we argue that our findings, when considered in conjunction with those from other settings, suggest that bacterial biomass may commonly represent only a minor component of total Corg in carbonaceous rocks.     

Thermal ecology and activity patterns of the short-horned lizard ( Phrynosoma douglassi ) and the sagebrush lizard ( Sceloporus graciosus ) in southeastern Idaho

A mark - recapture study of the short - horned lizard ( Phrynosoma douglassi ) and the sagebrush lizard ( Sceloporus graciosus ) was performed from 1976 to 1977 in southeastern Idaho. Both species had mean cloacal temperatures of approximately 33 C. However, P. douglassi had more variable cloacal temperatures, particularly during morning and evening periods. This was caused by differences in sleeping sites chosen by the two species. Adults of both species were active from mid - April through late August, with peak activity in June. Juvenile P. douglassi displayed a seasonal activity pattern similar to that of adults. Juvenile S. graciosus were most active later in the year (August), when adults were disappearing. In both species, young - of - the - year appeared in early to mid - August. Adult and juvenile P. douglassi were active during all daylight hours and displayed no activity peaks, whereas young - of - the - year displayed a bimodal activity pattern. Adult and juvenile S. graciosus were active over all daylight hours but had peak activity between 1200 and 1500 h. Ants ( Pogonomyrmex ) were the lizard's principle prey. However, only young - of - the - year P. douglassi had activity patterns that paralleled that of ants on their mounds.         

Assessing time series models for forecasting international migration: Lessons from the United Kingdom

Migration is one of the most unpredictable demographic processes. The aim of this article is to provide a blueprint for assessing various possible forecasting approaches in order to help safeguard producers and users of official migration statistics against misguided forecasts. To achieve that, we first evaluate the various existing approaches to modelling and forecasting of international migration flows. Subsequently, we present an empirical comparison of ex post performance of various forecasting methods, applied to international migration to and from the United Kingdom. The overarching goal is to assess the uncertainty of forecasts produced by using different forecasting methods, both in terms of their errors (biases) and calibration of uncertainty. The empirical assessment, comparing the results of various forecasting models against past migration estimates, confirms the intuition about weak predictability of migration, but also highlights varying levels of forecast errors for different migration streams. There is no single forecasting approach that would be well suited for different flows. We therefore recommend adopting a tailored approach to forecasts, and applying a risk management framework to their results, taking into account the levels of uncertainty of the individual flows, as well as the differences in their potential societal impact.     

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.