80 research outputs found

    An analysis of human cytomegalovirus gene family function

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    Human cytomegalovirus (HCMV) is a β-herpesvirus that causes complications in immuno-compromised individuals and is the leading infectious cause of birth defects. The HCMV genome contains 15 gene families, which contain between 2 to 14 members. One of these, the US12 gene family, consists of a sequential cluster of 10 genes (US12 to US21) that are highly conserved in clinical isolates. This family has roles in tropism and immune evasion and was recently found to regulate the cell surface expression of a wide array of immune ligands. This included the regulation of ligands for the natural killer (NK) cell activating receptors NKG2D and NKp30 (MICA and B7-H6 respectively), which were targeted by US18 and US20. To complement these mechanistic studies, a C-terminal V5 epitope tag was added to each US12 family gene within the HCMV Merlin genome. A large proportion of the US12 family were shown to be degraded within the cell, possibly within lysosomes, which suggests that they may interact with their targets proteins in order to redirect them for degradation. Expression of US12 family members was detectable by immunoblotting during an infection time-course, with many US12 family members expressed during the Tp3 temporal class of HCMV gene expression. Three members of the family were also demonstrated to be N-glycosylated during HCMV infection. The US12 family appear to have associations with the virion assembly compartment, and correspondingly, 7 US12 family members are found within the virion. Furthermore, the majority of the US12 family also show co-localisation with endoplasmic reticulum-derived membranes. These data build on our previous functional characterisation to give insights into the workings of this important HCMV gene family

    Immunogenicity and Protective Capacity of Sugar ABC Transporter Substrate-Binding Protein against Streptococcus suis Serotype 2, 7 and 9 Infection in Mice

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    Background: Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis

    Distinct and Overlapping Brain Areas Engaged during Value-Based, Mathematical, and Emotional Decision Processing.

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    When comparing between the values of different choices, human beings can rely on either more cognitive processes, such as using mathematical computation, or more affective processes, such as using emotion. However, the neural correlates of how these two types of processes operate during value-based decision-making remain unclear. In this study, we investigated the extent to which neural regions engaged during value-based decision-making overlap with those engaged during mathematical and emotional processing in a within-subject manner. In a functional magnetic resonance imaging experiment, participants viewed stimuli that always consisted of numbers and emotional faces that depicted two choices. Across tasks, participants decided between the two choices based on the expected value of the numbers, a mathematical result of the numbers, or the emotional face stimuli. We found that all three tasks commonly involved various cortical areas including frontal, parietal, motor, somatosensory, and visual regions. Critically, the mathematical task shared common areas with the value but not emotion task in bilateral striatum. Although the emotion task overlapped with the value task in parietal, motor, and sensory areas, the mathematical task also evoked responses in other areas within these same cortical structures. Minimal areas were uniquely engaged for the value task apart from the other two tasks. The emotion task elicited a more expansive area of neural activity whereas value and mathematical task responses were in more focal regions. Whole-brain spatial correlation analysis showed that valuative processing engaged functional brain responses more similarly to mathematical processing than emotional processing. While decisions on expected value entail both mathematical and emotional processing regions, mathematical processes have a more prominent contribution particularly in subcortical processes

    Creative and Stylistic Devices Employed by Children During a Storybook Narrative Task: A Cross-Cultural Study

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    Purpose: The purpose of this study was to analyze the effects of culture on the creative and stylistic features children employ when producing narratives based on wordless picture books. Method: Participants included 60 first- and second-grade African American, Latino American, and Caucasian children. A subset of narratives based on wordless picture books collected as part of a larger study was coded and analyzed for the following creative and stylistic conventions: organizational style (topic centered, linear, cyclical), dialogue (direct, indirect), reference to character relationships (nature, naming, conduct), embellishment (fantasy, suspense, conflict), and paralinguistic devices (expressive sounds, exclamatory utterances). Results: Many similarities and differences between ethnic groups were found. No significant differences were found between ethnic groups in organizational style or use of paralinguistic devices. African American children included more fantasy in their stories, Latino children named their characters more often, and Caucasian children made more references to the nature of character relationships. Conclusion: Even within the context of a highly structured narrative task based on wordless picture books, culture influences children’s production of narratives. Enhanced understanding of narrative structure, creativity, and style is necessary to provide ecologically valid narrative assessment and intervention for children from diverse cultural backgrounds

    BOLD Correlates of Trial-by-Trial Reaction Time Variability in Gray and White Matter: A Multi-Study fMRI Analysis

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    Reaction time (RT) is one of the most widely used measures of performance in experimental psychology, yet relatively few fMRI studies have included trial-by-trial differences in RT as a predictor variable in their analyses. Using a multi-study approach, we investigated whether there are brain regions that show a general relationship between trial-by-trial RT variability and activation across a range of cognitive tasks.The relation between trial-by-trial differences in RT and brain activation was modeled in five different fMRI datasets spanning a range of experimental tasks and stimulus modalities. Three main findings were identified. First, in a widely distributed set of gray and white matter regions, activation was delayed on trials with long RTs relative to short RTs, suggesting delayed initiation of underlying physiological processes. Second, in lateral and medial frontal regions, activation showed a "time-on-task" effect, increasing linearly as a function of RT. Finally, RT variability reliably modulated the BOLD signal not only in gray matter but also in diffuse regions of white matter.The results highlight the importance of modeling trial-by-trial RT in fMRI analyses and raise the possibility that RT variability may provide a powerful probe for investigating the previously elusive white matter BOLD signal

    What Women Want

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    Physical attractiveness has been shown to impact perceptions of stranger’s “sensitivity, kindness, intelligence, poise, and sociability,” (Bukley, 1983). Additionally, men who are perceived as more masculine are generally rated as more physically attractive (Urbaniak & Kilmann, 2006). Existing research supports that, across cultures, females find men perceived as having high status potential as more physically attractive (Elliot et al., 2010). The purpose of the current study was to analyze the effect of stereotyping on females’ perceptions of males. Female participants rated images of the same male model dressed in several current societal stereotypes (hipster, prep, cowboy, mountain man, and control). Each participant received one picture, which they rated on a series of characteristics including trustworthiness, overall likeability, and potential for success. Fifty female psychology students participated in the study as partial fulfillment of a course requirement. It was expected that the style of dress would significantly impact participant perceptions of the male model on attractiveness and all tested characteristics. Results are discussed in terms of first impressions and mate selection
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