Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time – an intra-subject analysis

Abstract Background Our previous work described the neural processes of motor response inhibition during a stop signal task (SST). Employing the race model, we computed the stop signal reaction time (SSRT) to index individuals' ability in inhibitory control. The pre-supplementary motor area (preSMA), which shows greater activity in individuals with short as compared to those with long SSRT, plays a role in mediating response inhibition. In contrast, the right inferior prefrontal cortex (rIFC) showed greater activity during stop success as compared to stop error. Here we further pursued this functional differentiation of preSMA and rIFC on the basis of an intra-subject approach. Results Of 65 subjects who participated in four sessions of the SST, we identified 30 individuals who showed a difference in SSRT but were identical in other aspects of stop signal performance between the first ("early") and last two ("late") sessions. By comparing regional brain activation between the two sessions, we confirmed greater preSMA but not rIFC activity during short as compared to long SSRT session within individuals. Furthermore, putamen, anterior cerebellum and middle/posterior cingulate cortex also showed greater activity in association with short SSRT. Conclusion These results are consistent with a role of medial prefrontal cortex in controlled action and inferior frontal cortex in orienting attention. We discussed these findings with respect to the process of attentional monitoring and inhibitory motor control during stop signal inhibition.</p

Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex

<p>Abstract</p> <p>Background</p> <p>To study the organization and interaction with the fusion domain (or fusion peptide, FP) of the transmembrane domain (TMD) of influenza virus envelope glycoprotein for its role in membrane fusion which is also essential in the cellular trafficking of biomolecules and sperm-egg fusion.</p> <p>Results</p> <p>The fluorescence and gel electrophoresis experiments revealed a tight self-assembly of TMD in the model membrane. A weak but non-random interaction between TMD and FP in the membrane was found. In the complex, the central TMD oligomer was packed by FP in an antiparallel fashion. FP insertion into the membrane was altered by binding to TMD. An infrared study exhibited an enhanced membrane perturbation by the complex formation. A model was built to illustrate the role of TMD in the late stages of influenza virus-mediated membrane fusion reaction.</p> <p>Conclusion</p> <p>The TMD oligomer anchors the fusion protein in the membrane with minimal destabilization to the membrane. Upon associating with FP, the complex exerts a synergistic effect on the membrane perturbation. This effect is likely to contribute to the complete membrane fusion during the late phase of fusion protein-induced fusion cascade. The results presented in the work characterize the nature of the interaction of TMD with the membrane and TMD in a complex with FP in the steps leading to pore initiation and dilation during virus-induced fusion. Our data and proposed fusion model highlight the key role of TMD-FP interaction and have implications on the fusion reaction mediated by other type I viral fusion proteins. Understanding the molecular mechanism of membrane fusion may assist in the design of anti-viral drugs.</p

Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing

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Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex

<p>Abstract</p> <p>Background</p> <p>To study the organization and interaction with the fusion domain (or fusion peptide, FP) of the transmembrane domain (TMD) of influenza virus envelope glycoprotein for its role in membrane fusion which is also essential in the cellular trafficking of biomolecules and sperm-egg fusion.</p> <p>Results</p> <p>The fluorescence and gel electrophoresis experiments revealed a tight self-assembly of TMD in the model membrane. A weak but non-random interaction between TMD and FP in the membrane was found. In the complex, the central TMD oligomer was packed by FP in an antiparallel fashion. FP insertion into the membrane was altered by binding to TMD. An infrared study exhibited an enhanced membrane perturbation by the complex formation. A model was built to illustrate the role of TMD in the late stages of influenza virus-mediated membrane fusion reaction.</p> <p>Conclusion</p> <p>The TMD oligomer anchors the fusion protein in the membrane with minimal destabilization to the membrane. Upon associating with FP, the complex exerts a synergistic effect on the membrane perturbation. This effect is likely to contribute to the complete membrane fusion during the late phase of fusion protein-induced fusion cascade. The results presented in the work characterize the nature of the interaction of TMD with the membrane and TMD in a complex with FP in the steps leading to pore initiation and dilation during virus-induced fusion. Our data and proposed fusion model highlight the key role of TMD-FP interaction and have implications on the fusion reaction mediated by other type I viral fusion proteins. Understanding the molecular mechanism of membrane fusion may assist in the design of anti-viral drugs.</p

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor

Engaging Undergraduates in Science Research: Not Just About Faculty Willingness.

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty members' likelihood of engaging undergraduates in their research project(s). Using data from the Higher Education Research Institute's 2007-2008 Faculty Survey, we employ hierarchical generalized linear modeling to analyze data from 4,832 science, technology, engineering, and mathematics (STEM) faculty across 194 institutions to examine how organizational citizenship behavior theory and social exchange theory relate to mentoring students in research. Key findings show that faculty who work in the life sciences and those who receive government funding for their research are more likely to involve undergraduates in their research project(s). In addition, faculty at liberal arts or historically Black colleges are significantly more likely to involve undergraduate students in research. Implications for advancing undergraduate research opportunities are discussed

Evaluation of dog owners' perceptions concerning radiation therapy

<p>Abstract</p> <p>Background</p> <p>External radiation therapy (RT) has been available for small animals in Sweden since 2006. This study was designed to obtain information on owner experiences and perceptions related to RT of cancer in their dogs. Another survey was used to determine the attitudes about use of RT in a group of Swedish veterinarians. Their responses were analyzed and compared to their level of knowledge of oncology and RT.</p> <p>Methods</p> <p>Owners of all dogs (n = 23) who had undergone RT for malignancy at Jönköping Small Animal Hospital between March 2006 to September 2007 were interviewed. A questionnaire was given to a selected group of veterinarians.</p> <p>Results</p> <p>All 23 owners responded. All owners thought that their dog did well during RT and most that their dog was also fine during the following phase when acute RT-related skin reactions occur and heal. Three owners stated that their dog had pain that negatively impacted quality of life because of radiation dermatitis. Five owners reported that RT positively impacted quality of life of the dog during the first weeks after RT because palliation was achieved. The owners were not disturbed by the efforts required of them. All but one owner (22 of 23) stated that they would make the same decision about RT again if a similar situation occurred. The most important factor for this decision was the chance to delay occurrence of tumour-related discomfort. The chance for cure was of less importance but still essential, followed by expected side effects. Time commitments, travel, number of treatments required and financial cost; all had low impact. The veterinarian survey showed that less background knowledge of small animal oncology/RT was associated with more negative expectations of RT for small animals.</p> <p>Conclusion</p> <p>The results show that for these owners, RT was a worthwhile treatment modality and that the discomfort for the dog was manageable and acceptable relative to the benefits. Improved continuing education about small animal RT in Sweden will likely result in increased evidence-based and positive treatment recommendations concerning RT by veterinarians.</p