Single molecule studies of protein unfolding in highly saline solutions

Life on earth has been found thriving in a number of extreme environments, including those of high salinity, high and low temperatures and pH, and high pressure. Organisms which live in the presence of large quantities of salt are known as halophilic (meaning salt-loving), such as in the Dead Sea. Proteins are fundamental components of all living organisms. They are large, complex molecules that carry out many processes within a cell. Halophilic proteins are of great interest due to their ability to remain soluble, flexible and functional under highly saline conditions. Intriguingly, these proteins are unstable in a low saline environment, suggesting a delicate balance between the intermolecular interactions of the protein, salt and solvent. How have halophilic proteins adapted to survive in highly saline environments? To probe the effect of salt on the mechanical stability of a protein, a combination of molecular biology and single molecule force spectroscopy (SMFS) was used. Protein engineering was utilised to create chimeric polyprotein constructs including a obligate halophilic and a mesophilic protein. SMFS experiments have been carried out using these polyprotein constructs in 0.5 M and 2 M KCl. The studies suggest that an increase in the hydrophobic interactions of a mesophilic protein cause an increase in its mechanical stability. The results also indicate that an obligate halophilic protein does not have an increased mechanical stability in the increased salt concentration. Further studies in combination with molecular dynamics simulations have the potential to gain atomistic information on the mechanical unfolding behaviour of a halophilic protein

A gene × gene interaction between DRD2 and DRD4 is associated with conduct disorder and antisocial behavior in males

<p>Abstract</p> <p>Background</p> <p>Antisocial behaviors are complex polygenic phenotypes that are due to a multifactorial arrangement of genetic polymorphisms. Little empirical research, however, has been undertaken that examines gene × gene interactions in the etiology of conduct disorder and antisocial behavior. This study examined whether adolescent conduct disorder and adult antisocial behavior were related to the dopamine D2 receptor polymorphism (DRD2) and the dopamine D4 receptor polymorphism (DRD4).</p> <p>Methods</p> <p>A sample of 872 male participants from the National Longitudinal Study of Adolescent Health (Add Health) completed self-report questionnaires that tapped adolescent conduct disorder and adult antisocial behavior. DNA was genotyped for DRD2 and DRD4.</p> <p>Results</p> <p>Multivariate regression analysis revealed that neither DRD2 nor DRD4 had significant independent effects on conduct disorder or antisocial behavior. However, DRD2 interacted with DRD4 to predict variation in adolescent conduct disorder and in adult antisocial behavior.</p> <p>Conclusion</p> <p>The results suggest that a gene × gene interaction between DRD2 and DRD4 is associated with the development of conduct disorder and adult antisocial behavior in males.</p

A brave new world for an old world pest: Helicoverpa armigera (Lepidoptera: Noctuidae) in Brazil

The highly polyphagous Old World cotton bollworm Helicoverpa armigera is a quarantine agricultural pest for the American continents. Historically H. armigera is thought to have colonised the American continents around 1.5 to 2 million years ago, leading to the current H. zea populations on the American continents. The relatively recent species divergence history is evident in mating compatibility between H. zea and H. armigera under laboratory conditions. Despite periodic interceptions of H. armigera into North America, this pest species is not believed to have successfully established significant populations on either continent. In this study, we provide molecular evidence via mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) and cytochrome b (Cyt b) partial gene sequences for the successful recent incursion of H. armigera into the New World, with individuals being detected at two sites (Primavera do Leste, Pedra Preta) within the State of Mato Grosso in Brazil. The mtDNA COI and Cyt b haplotypes detected in the Brazilian H. armigera individuals are common throughout the Old World, thus precluding identification of the founder populations. Combining the two partial mtDNA gene sequences showed that at least two matrilines are present in Brazil, while the inclusion of three nuclear DNA Exon-Primed Intron-Crossing (EPIC) markers identified a further two possible matrilines in our samples. The economic, biosecurity, resistance management, ecological and evolutionary implications of this incursion are discussed in relation to the current agricultural practices in the Americas

A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype

<p>Abstract</p> <p>Background</p> <p>The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p> <p>Results</p> <p>To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it>tau-lacZ </it>reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it>reeler</it>. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it>Emx2 </it>gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p> <p>Conclusions</p> <p>These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it>Emx2 </it>mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p> <p>See Commentary: <url>http://www.biomedcentral.com/1741-7007/9/1</url></p

The Grizzly, October 28, 2010

Junot Diaz Speaks to Ursinus Campus • Berman Celebrates 20th Anniversary with Open House • Active Minds Talks About Mental Illness • Ursinus Music Department Active on Campus • UC Homecoming 2010 • Senior Explores Middle East • Students Celebrate Writing • Internship Spotlight: Jason Ward • Finally, Ursinus Creates an Arena for Race Relations • Once Upon a Potty • Letter to the Editor • Hey UC, Give Me a [Fall] Break • Bears Travel in Packs During Cross Country Season • Women\u27s Rugby Takes on Scranton This Saturdayhttps://digitalcommons.ursinus.edu/grizzlynews/1822/thumbnail.jp

Predictors of Community Therapists\u27 Use of Therapy Techniques in a Large Public Mental Health System

Importance Few studies have examined the effects of individual and organizational characteristics on the use of evidence-based practices in mental health care. Improved understanding of these factors could guide future implementation efforts to ensure effective adoption, implementation, and sustainment of evidence-based practices. Objective To estimate the relative contribution of individual and organizational factors on therapist self-reported use of cognitive-behavioral, family, and psychodynamic therapy techniques within the context of a large-scale effort to increase use of evidence-based practices in an urban public mental health system serving youth and families. Design, Setting, and Participants In this observational, cross-sectional study of 23 organizations, data were collected from March 1 through July 25, 2013. We used purposive sampling to recruit the 29 largest child-serving agencies, which together serve approximately 80% of youth receiving publically funded mental health care. The final sample included 19 agencies with 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators. Main Outcomes and Measures Therapist self-reported use of cognitive-behavioral, family, and psychodynamic therapy techniques, as measured by the Therapist Procedures Checklist–Family Revised. Results Individual factors accounted for the following percentages of the overall variation: cognitive-behavioral therapy techniques, 16%; family therapy techniques, 7%; and psychodynamic therapy techniques, 20%. Organizational factors accounted for the following percentages of the overall variation: cognitive-behavioral therapy techniques, 23%; family therapy techniques, 19%; and psychodynamic therapy techniques, 7%. Older therapists and therapists with more open attitudes were more likely to endorse use of cognitive-behavioral therapy techniques, as were those in organizations that had spent fewer years participating in evidence-based practice initiatives, had more resistant cultures, and had more functional climates. Women were more likely to endorse use of family therapy techniques, as were those in organizations employing more fee-for-service staff and with more stressful climates. Therapists with more divergent attitudes and less knowledge about evidence-based practices were more likely to use psychodynamic therapy techniques. Conclusions and Relevance This study suggests that individual and organizational factors are important in explaining therapist behavior and use of evidence-based practices, but the relative importance varies by therapeutic technique