Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.     

Avian tumor virus interactions with chicken fibroblast plasma membranes

A method is described which will rapidly measure the binding of avian tumor viruses (ATV) to plasma membrane receptors. With this procedure it may be shown that Rous sarcoma virus pseudotypes bind to protease-labile, heat-stable structures on the surface of chicken embryo fibroblast (CEF) plasma membranes. The binding sites for ATV subgroups A and B appear distinct, and membranes from genetically resistant CEF bind as well those of sensitive CEF.     

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair.     

Does forest fragmentation cause an increase in forest temperature?

Forest fragmentation is considered by many to be a primary cause of the current biodiversity crisis. The underlying mechanisms are poorly known, but a potentially important one is associated with altered thermal conditions within the remaining forest patches, especially at forest edges. Yet, large uncertainty remains about the effect of fragmentation on forest temperature, as it is unclear whether temperature decreases from forest edge to forest interior, and whether this local gradient scales up to an effect of fragmentation (landscape attribute) on temperature. We calculated the effect size (correlation coefficient) of distance from forest edge on air temperature, and tested for differences among forest types surrounded by different matrices using meta-analysis techniques. We found a negative edge-interior temperature gradient, but correlation coefficients were highly variable, and significant only for temperate and tropical forests surrounded by a highly contrasting open matrix. Nevertheless, it is unclear if these local-scale changes in temperature can be scaled up to an effect of fragmentation on temperature. Although it may be valid when considering “fragmentation” as forest loss only, the landscape-scale inference is not so clear when we consider the second aspect of fragmentation, where a given amount of forest is divided into a large number of small patches (fragmentation per se). Therefore, care is needed when assuming that fragmentation changes forest temperature, as thermal changes at forest edges depend on forest type and matrix composition, and it is still uncertain if this local gradient can be scaled up to the landscape.     

"Part and Parcel of Being a Woman": Female Urinary Incontinence and Constructions of Control

This article draws on extensive interviews with middle-aged Australian women experiencing urinary incontinence. Our discussion derives from the difficulties women face in seeking advice on the management of incontinence, as a consequence of their perception that the condition is an inevitability, a "normal" part of being female. Women do not, on the whole, support a single cause for incontinence but, rather, explain its incidence in terms of personal history, which may include childbearing and parturition, menopause and aging, and early socialization. In addition, women link their own continence problems with perceived personal failings (e.g., lack of exercise, being overweight) and, hence, see the condition as a symbol of their lack of moral worth. Following this, women's understandings of the relationship of incontinence to their social membership extend far beyond the difficulties of disguising their physical problems.     

Down syndrome: interaction between culture, demography, and biology in determining the prevalence of a genetic trait

The incidence of Down syndrome (DS) at conception is highly dependent upon the maternal age distribution and age-specific pregnancy rates. Live-birth prevalence of DS reflects these factors and fetal deaths. Since the introduction of prenatal diagnosis in the early 1970s, the role of fetal deaths in the equation has increased. Between 1920 and the early 1980s, DS live-birth prevalence decreased in many populations due to declining fertility rates, particularly among older women. In the late-1970s the trend reversed, as the median age of populations and birth rates among older women steadily increased. This paper illustrates these interactions using data we have analyzed for New York State (NYS) and comparative data obtained from the literature. Between 1983 and 1997 DS live-birth prevalence in NYS remained stable at about 9.9 per 10,000 live births. The number of prenatal tests performed increased by 158%, and the number of DS fetuses detected prenatally more than quadrupled. Fertility rates of women aged 35-49 continued to increase. The proportion of DS cases born to these older mothers increased from 23% in 1985 to 43% in 1997. We estimated that without prenatal diagnosis, DS live-birth prevalence would have been 17.0 per 10,000 live births by 1995. Cultural factors influence demographic trends, birthing technologies, physician practices, and women's decision-making regarding prenatal screening and diagnosis for DS.     

Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity

Prenatal cytomegalovirus infection may cause pregnancy complications such as intrauterine growth restriction and birth defects. How virus from the mother traverses the placenta is unknown. PCR analysis of biopsy specimens of the maternal-fetal interface revealed that DNA sequences from cytomegalovirus were commonly found with those of herpes simplex viruses and pathogenic bacteria. Cytomegalovirus DNA and infected cell proteins were found more often in the decidua than in the placenta, suggesting that the uterus functions as a reservoir for infection. In women with low neutralizing titers, cytomegalovirus replicated in diverse decidual cells and placental trophoblasts and capillaries. In women with intermediate to high neutralizing titers, decidual infection was suppressed and the placenta was spared. Overall, cytomegalovirus virions and maternal immunoglobulin G were detected in syncytiotrophoblasts, villus core macrophages, and dendritic cells. These results suggest that the outcome of cytomegalovirus infection depends on the presence of other pathogens and coordinated immune responses to viral replication at the maternal-fetal interface.