Variations in DNA elucidate molecular networks that cause disease

Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage-enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl), lactamase beta (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors.     

A stability limit for the atmospheres of giant extrasolar planets

Recent observations of the planet HD209458b indicate that it is surrounded by an expanded atmosphere of atomic hydrogen that is escaping hydrodynamically. Theoretically, it has been shown that such escape is possible at least inside an orbit of 0.1 au (refs 4 and 5), and also that H3+ ions play a crucial role in cooling the upper atmosphere. Jupiter's atmosphere is stable, so somewhere between 5 and 0.1 au there must be a crossover between stability and instability. Here we show that there is a sharp breakdown in atmospheric stability between 0.14 and 0.16 au for a Jupiter-like planet orbiting a solar-type star. These results are in contrast to earlier modelling that implied much higher thermospheric temperatures and more significant evaporation farther from the star. (We use a three-dimensional, time-dependent coupled thermosphere-ionosphere model and properly include cooling by H3+ ions, allowing us to model globally the redistribution of heat and changes in molecular composition.) Between 0.2 and 0.16 au cooling by H3+ ions balances heating by the star, but inside 0.16 au molecular hydrogen dissociates thermally, suppressing the formation of H3+ and effectively shutting down that mode of cooling.     

Pulse gas alignment and AFM manipulation of single-wall carbon nanotube

In the fabrication process of nanoelectronic device arrays based on single-wall carbon nanotube （SWCNT）, oriented alignment of SWCNTs and property modification of metallic SWCNTs in the array are the key problems to be solved. Pulse gas alignment with substrate downward tilt is proposed to realize the controllable alignment of SWCNTs. Experimental results demonstrate that 84% SWCNTs are aligned in -15°- 15° angular to the pulse gas direction. A modified nanomanipulation technology based on atomic force microscope （AFM） is utilized to perform various kinds of SWCNT manipulation, such as SWCNT separation from the ＂Y＂ CNT, catalyst removal from the SWCNT end, continual nano buckles fabrication on SWCNT and even stretching to break, which provides a feasible way to modify the size, shape and the electrical property of SWCNTs.     

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.     

Age differences at marriage and divorce

This article explores the age difference of marrying and divorcing couples, calculated by subtracting the wife's age from the husband's. Age difference is of interest in the study of families and partnership behaviour. It is also important because of its link with broader socio-demographic changes, such as population ageing, delayed fertility and the provision of care. The main finding is that between 1963 and 2005, the distribution of age differences for all marriages is very similar in each year to the distribution of age differences for the subset of couples who married in that year, but have since divorced. While there is some evidence of small variations in the proportion of marriages that end in divorce by age difference, there does not seem to be evidence of a strong association.     

A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15

F cells measure the presence of fetal hemoglobin, a heritable quantitative trait in adults that accounts for substantial phenotypic diversity of sickle cell disease and beta thalassemia. We applied a genome-wide association mapping strategy to individuals with contrasting extreme trait values and mapped a new F cell quantitative trait locus to BCL11A, which encodes a zinc-finger protein, on chromosome 2p15. The 2p15 BCL11A quantitative trait locus accounts for 15.1% of the trait variance.     

Understanding recent trends in marriage

This article explores recent trends in marriage. Following consistent falls in marriage rates in the last quarter of the 20th century the early years of this century have seen some relatively large fluctuations in marriage numbers and rates. This article illustrates some of the recent trends in marriage. One innovation is that it presents marriage data by month, controlled for the effect of peak marriage days in the week. It also discusses a recent legislative change, affecting those subject to immigration control that wish to marry, which may be one of many factors affecting latest marriage trends. Readers should bear in mind that the 2005 data shown in the article are provisional.     

High mutation rates have driven extensive structural polymorphism among human Y chromosomes

Although much structural polymorphism in the human genome has been catalogued, the kinetics of underlying change remain largely unexplored. Because human Y chromosomes are clonally inherited, it has been possible to capture their detailed relationships in a robust, worldwide genealogical tree. Examination of structural variation across this tree opens avenues for investigating rates of underlying mutations. We selected one Y chromosome from each of 47 branches of this tree and searched for large-scale variation. Four chromosomal regions showed extensive variation resulting from numerous large-scale mutations. Within the tree encompassed by the studied chromosomes, the distal-Yq heterochromatin changed length > or = 12 times, the TSPY gene array changed length > or = 23 times, the 3.6-Mb IR3/IR3 region changed orientation > or = 12 times and the AZFc region was rearranged > or = 20 times. After determining the total time spanned by all branches of this tree (approximately 1.3 million years or 52,000 generations), we converted these mutation counts to lower bounds on rates: > or = 2.3 x 10(-4), > or = 4.4 x 10(-4), > or = 2.3 x 10(-4) and > or = 3.8 x 10(-4) large-scale mutations per father-to-son Y transmission, respectively. Thus, high mutation rates have driven extensive structural polymorphism among human Y chromosomes. At the same time, we found limited variation in the copy number of Y-linked genes, which raises the possibility of selective constraints.