Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial

Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Apoptotic Engulfment Pathway and Schizophrenia

Background: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. Methodology/Principal Findings: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. Conclusions/Significance: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease. © 2009 Chen et al

Underwater source localization in the presence of strong interference

The underwater localization of a broadband target in the presence of strong interference and noise has been widely investigated. A novel clutter suppression approach based on oblique projections is proposed, exploiting the prior information of the expected target response. The method uses a generalised likelihood ratio formulation to select the oblique projection best matching the measured data. The performance of the proposed method is verified through numerical examples and measured sonar data. The results indicate that the method provides good performance for time difference of arrival estimation and target localization under low signal to clutter ratio as compared to existing methods

Influence of Heat Treatments on Microstructure and Mechanical Properties of Ti–26Nb Alloy Elaborated In Situ by Laser Additive Manufacturing with Ti and Nb Mixed Powder

In the present work, a Ti–26Nb alloy was elaborated in situ by laser additive manufacturing (LAM) with Ti and Nb mixed powders. The alloys were annealed at temperatures ranging from 650 °C to 925 °C, and the effects of the annealing temperature on the microstructure and mechanical properties were investigated. It has been found that the microstructure of the as-deposited alloy obtained in the present conditions is characterized by columnar prior β grains with a relatively strong <001> fiber texture in the build direction. The as-deposited alloy exhibits extremely high strength, and its ultimate tensile strength and yield strength are about 799 MPa and 768 MPa, respectively. The annealing temperature has significant effects on the microstructure and mechanical properties of the alloys. Annealing treatment can promote the dissolution of unmelted Nb particles and eliminate the micro-segregation of Nb at the elliptical-shaped grain boundaries, while increasing the grain size of the alloy. With an increase in annealing temperature, the strength of the alloy decreases but the ductility increases. The alloy annealed at 850 °C exhibits a balance of strength and ductility

Key Technology for Liquid Spawn Production and Green and High-yield Cultivation of Pleurotus eryngii

[Objectives] Pleurotus eryngii is currently the second largest edible fungus variety cultivated in China, and it mainly adopts the bag cultivation mode. This study aims to effectively solve the problems of high cost of solid spawn, long spawn production cycle, low application level of green and high-yield cultivation technology and equipment, and unstable output and quality in the factory production process and to further promote industrial upgrading. [Methods] Since June, 2018, a series of research and technical optimizations had been carried out by a technical research team consisting of personnels from Vegetable Office of Guannan County, Institute of Edible Fungi of Shanghai Academy of Agricultural Sciences and Jiangsu Xiangru Biotechnology Co., Ltd., around the production of liquid spawn, introduction of excellent varieties of P. eryngii, medium pretreatment, autoclaving, clean room inoculation, digital cultivation, harvesting, packaging, etc. [Results] The key technology of industrial production, liquid spawn production and green and high-yield cultivation of P. eryngii are summarized. [Conclusions] The economic benefit of liquid spawn of P. eryngii is extremely considerable compared with liquid spawns such as branch spawn

Biodegradable ternary Zn–3Ge–0.5X (X=Cu, Mg, and Fe) alloys for orthopedic applications

Biodegradable zinc (Zn) and its alloys have great potential to be used for orthopedic applications due to their suitable degradation rate and good biocompatibility. However, pure Zn has insufficient mechanical properties, such as low strength and hardness, and poor plasticity, which limits its clinical applications. Here, we report on a new series of ternary Zn–3Ge–0.5X (X=Cu, Mg, and Fe) alloys aiming to achieve good corrosion resistance and biocompatibility, and enhanced mechanical properties via micro-alloying with copper (Cu), magnesium (Mg), and iron (Fe). Hot-rolling has also been applied to the new ternary alloys to further enhance their mechanical properties. Mechanical testing results indicate that both the strength and hardness of hot-rolled Zn–3Ge are significantly improved with micro-alloying of Cu, Mg, and Fe; of which the hot-rolled Zn–3Ge–0.5Mg exhibits the highest ultimate tensile strength of 253.4 MPa and yield strength of 208.5 MPa among all the alloys, 25.9% and 44.7% higher than those of the hot-rolled Zn–3Ge. The degradation rate of the as-cast alloys is lower than that of the hot-rolled alloys in Hanks’ solution for 1 month and the hot-rolled Zn–3Ge–0.5Mg alloy exhibits the highest degradation rate of 0.075 mm/y. CCK-8 assay using MG-63 cells indicates that the diluted extracts of Zn–3Ge–0.5X (X=Cu, Mg, and Fe) alloys with concentrations of 12.5% and 25% exhibit no or slight cytotoxicity, and the diluted extracts of Zn–3Ge–0.5Cu alloys show high cell viability of over 100%, showing the best cytocompatibility