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

Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).

<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p

Evolution of predator dispersal in relation to spatio-temporal prey dynamics : how not to get stuck in the wrong place!

Peer reviewedPublisher PD

Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response

Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain that can persist for weeks, months, or even years. Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation of Rag1(−/−) mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type and Rag1(−/−) mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans

Quail Genomics: a knowledgebase for Northern bobwhite

<p>Abstract</p> <p>Background</p> <p>The Quail Genomics knowledgebase (<url>http://www.quailgenomics.info</url>) has been initiated to share and develop functional genomic data for Northern bobwhite (<it>Colinus virginianus</it>). This web-based platform has been designed to allow researchers to perform analysis and curate genomic information for this non-model species that has little supporting information in GenBank.</p> <p>Description</p> <p>A multi-tissue, normalized cDNA library generated for Northern bobwhite was sequenced using 454 Life Sciences next generation sequencing. The Quail Genomics knowledgebase represents the 478,142 raw ESTs generated from the sequencing effort in addition to assembled nucleotide and protein sequences including 21,980 unigenes annotated with meta-data. A normalized MySQL relational database was established to provide comprehensive search parameters where meta-data can be retrieved using functional and structural information annotation such as gene name, pathways and protein domain. Additionally, blast hit cutoff levels and microarray expression data are available for batch searches. A Gene Ontology (GO) browser from Amigo is locally hosted providing 8,825 unigenes that are putative orthologs to chicken genes. In an effort to address over abundance of Northern bobwhite unigenes (71,384) caused by non-overlapping contigs and singletons, we have built a pipeline that generates scaffolds/supercontigs by aligning partial sequence fragments against the indexed protein database of chicken to build longer sequences that can be visualized in a web browser. </p> <p>Conclusion</p> <p>Our effort provides a central repository for storage and a platform for functional interrogation of the Northern bobwhite sequences providing comprehensive GO annotations, meta-data and a scaffold building pipeline. The Quail Genomics knowledgebase will be integrated with Japanese quail (<it>Coturnix coturnix</it>) data in future builds and incorporate a broader platform for these avian species. </p

Post-supereruption recovery at Toba Caldera

Large calderas, or supervolcanoes, are sites of the most catastrophic and hazardous events on Earth, yet the temporal details of post-supereruption activity, or resurgence, remain largely unknown, limiting our ability to understand how supervolcanoes work and address their hazards. Toba Caldera, Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr, climactically erupting ~74 ka. Since the supereruption, Toba has been in a state of resurgence but its magmatic and uplift history has remained unclear. Here we reveal that new 14 C, zircon U-Th crystallization and (U-Th)/He ages show resurgence commenced at 69.7±4.5 ka and continued until at least ~2.7 ka, progressing westward across the caldera, as reflected by post-caldera effusive lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba, Sinabung, shows strong geochemical kinship with Toba, and zircons from recent eruption products suggest Toba's climactic magma reservoir extends beneath Sinabung and is being tapped during eruptions

Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets

Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected

Early Adolescent Depressive Symptoms: Prediction from Clique Isolation, Loneliness, and Perceived Social Acceptance

This study examined whether clique isolation predicted an increase in depressive symptoms and whether this association was mediated by loneliness and perceived social acceptance in 310 children followed from age 11–14 years. Clique isolation was identified through social network analysis, whereas depressive symptoms, loneliness, and perceived social acceptance were assessed using self ratings. While accounting for initial levels of depressive symptoms, peer rejection, and friendlessness at age 11 years, a high probability of being isolated from cliques from age 11 to 13 years predicted depressive symptoms at age 14 years. The link between clique isolation and depressive symptoms was mediated by loneliness, but not by perceived social acceptance. No sex differences were found in the associations between clique isolation and depressive symptoms. These results suggest that clique isolation is a social risk factor for the escalation of depressive symptoms in early adolescence. Implications for research and prevention are discussed