Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network (GAIN) initiative of the US Foundation for the National Institutes of Health, we conducted a genomewide association study of 435,291 SNPs genotyped in 1,738 MDD cases and 1,802 controls selected to be at low liability for MDD. Eleven of the top 200 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and plays an important role in monoaminergic neurotransmission in the brain) with p-values of 7.7×10−7 for rs2715148 and 1.2×10−6 for rs2522833. We undertook replication of SNPs in this region in 5 independent samples (6,079 MDD independent cases and 5,893 controls) but no SNP exceeded the replication significance threshold when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the original sample with the sample of greatest similarity yielded p=6.4×10−8 for the non-synonymous SNP rs2522833 that gives rise to a serine to alanine substitution near a C2 calcium-binding-domain of the PCLO protein. With the integrated replication effort, we present a specific hypothesis for further studies.

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On 12 May, 2008, a devastating earthquake registering 8.0 on the Richter scale occurred in Sichuan Province, China, taking tens of thousands of lives and destroying the homes of millions of people. Many of the deceased were children, particular children less than five years old who were more vulnerable to such a huge disaster than the adult. In order to obtain information specifically relevant to further researches and future preventive measures, potential risk factors associated with earthquake-related child mortality need to be identified. We used four geographical detectors (risk detector, factor detector, ecological detector, and interaction detector) based on spatial variation analysis of some potential factors to assess their effects on the under-five mortality. It was found that three factors are responsible for child mortality: earthquake intensity, collapsed house, and slope. The study, despite some limitations, has important implications for both researchers and policy makers.

Missing genotype data arise in association studies when the single-nucleotide polymorphisms (SNPs) on the genotyping platform are not assayed successfully, when the SNPs of interest are not on the platform, or when total sequence variation is determined only on a small fraction of individuals. We present a simple and flexible likelihood framework to study SNP-disease associations with such missing genotype data. Our likelihood makes full use of all available data in case-control studies and reference panels (e.g., the HapMap), and it properly accounts for the biased nature of the case-control sampling as well as the uncertainty in inferring unknown variants. The corresponding maximum-likelihood estimators for genetic effects and gene-environment interactions are unbiased and statistically efficient. We developed fast and stable numerical algorithms to calculate the maximum-likelihood estimators and their variances, and we implemented these algorithms in a freely available computer program. Simulation studies demonstrated that the new approach is more powerful than existing methods while providing accurate control of the type I error. An application to a case-control study on rheumatoid arthritis revealed several loci that deserve further investigations.

The native structure of potato spindle tuber viroid (PSTVd) contains a series of short double helices and small internal loops that are organized into five structural domains. Nucleotides within the pathogenicity domain are known to play a critical role in modulating PSTVd symptom expression, and it has been suggested that disruption of a comparatively unstable "premelting region" within the pathogenicity domain may be required for disease induction. We have used a combination of quantitative bioassays, temperature gradient gel electrophoresis of circularized RNA transcripts, and thermodynamic calculations to compare the biological and structural properties of 12 representative PSTVd sequence variants. Certain mutations appeared to act indirectly, downregulating pathogenicity by suppressing the rate of PSTVd replication/accumulation. The effects of other mutations appeared to be more direct, but there was no consistent correlation between symptom severity and melting temperature. Taking into account the three-dimensional shape of RNA helices, comparison of the optimal secondary structures for these variants point to major differences in the geometry of their pathogenicity domains; i.e., variants producing intermediate symptoms possess a linear arrangement of three consecutive helices, whereas for variants producing mild or severe symptoms this domain is bent in opposing directions. Such alterations in RNA structure together with concomitant alterations in RNA-protein interaction(s) may be the primary cause of viroid pathogenicity.

Hydrogen evolution reaction (HER) was intensified to produce bubbles as dynamic templates for the preparation of foamed porous copper (FPCu) in acidic cupric electrolyte. The macroscopic morphologies of FPCu, including pore size distribution and pore density, were determined by the bubble diameter. Bubble assemble behavior was the most important in overall process of gas evolution. Growth of hydrogen bubbles caused coalescence of bubbles and resulted in size increment of the templates. Furthermore, bubble behavior was in tight relation with residence time and current density. Results showed that the morphologies were dependent on deposition time and current density. Small pores in FPCu were attributed to the un-coalesced bubbles and large pores were ascribed to the coalesced bubbles. The embedding and nesting of small holes by the large ones contributed to the formation of hierarchical porous framework. A “stack up layers” model was proposed to illuminate the morphological transformation of FPCu from two-dimensional structure to 3-dimensional framework. Understanding of this model facilitated the preparation of macroporous copper with favorable morphologies.

BackgroundSchistosomiasis japonica still remains of public health and economic significance in China, especially in the lake and marshland areas along the Yangtze River Basin, where the control of transmission has proven difficult. In the study, we investigated spatio-temporal variations of S. japonicum infection risk in Anhui Province and assessed the associations of the disease with key environmental factors with the aim of understanding the mechanism of the disease and seeking clues to effective and sustainable schistosomiasis control.Methodology/Principal FindingsInfection data of schistosomiasis from annual conventional surveys were obtained at the village level in Anhui Province, China, from 2000 to 2010 and used in combination with environmental data. The spatio-temporal kriging model was used to assess how these environmental factors affected the spatio-temporal pattern of schistosomiasis risk. Our results suggested that seasonal variation of the normalized difference vegetation index (NDVI), seasonal variation of land surface temperature at daytime (LSTD), and distance to the Yangtze River were negatively significantly associated with risk of schistosomiasis. Predictive maps showed that schistosomiasis prevalence remained at a low level and schistosomiasis risk mainly evolved along the Yangtze River. Schistosomiasis risk also followed a focal spatial pattern, fluctuating temporally with a peak (the largest spatial extent) in 2005 and then contracting gradually but with a scattered distribution until 2010.ConclusionThe fitted spatio-temporal kriging model can capture variations of schistosomiasis risk over space and time. Combined with techniques of geographic information system (GIS) and remote sensing (RS), this approach facilitates and enriches risk modeling of schistosomiasis, which in turn helps to identify prior areas for effective and sustainable control of schistosomiasis in Anhui Province and perhaps elsewhere in China.

The preparation, by a freeze-thaw method, of new graphite/isobutylene-isoprene rubber (IIR) sorbents for oil and organic liquid is described. Graphite was expected to improve the adsorption properties. The cryogels were prepared by solution crosslinking IIR rubber in the presence of graphite in benzene at various temperatures, using sulfur monochloride as the crosslinker, and characterized by SEM and contact angle measurements. The dried cryogels, with interconnected macropores were sponge-like soft materials, with excellent buoyancy and hydrophobicity. They also showed excellent sorption characteristics, with the best sample exhibiting maximum sorption capacities of 17.8 g g(-1) for crude oil, 21.6 g g(-1) for diesel oil, and 23.4 g g(-1) for lubricating oil, respectively. The samples also showed excellent sorption capability for organic liquids, absorbing up to around twenty times their own mass. After rapid and effective desorption, taking just 3-5 h, the cryogels were recovered. They could also be reused more than 30 times by simply centrifuging to remove the sorbed liquid. These characteristics mean that the cryogels prepared in this study are promising materials for removal of large-scale oil or toxic organic spills.