Protein Kinase Cε Is Required for Macrophage Activation and Defense Against Bacterial Infection

To assess directly the role of protein kinase C (PKC)ε in the immune system, we generated mice that carried a homozygous disruption of the PKCε locus. PKCε−/− animals appeared normal and were generally healthy, although female mice frequently developed a bacterial infection of the uterus. Macrophages from PKCε−/− animals demonstrated a severely attenuated response to lipopolysaccharide (LPS) and interferon (IFN)γ, characterized by a dramatic reduction in the generation of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Further analysis revealed that LPS-stimulated macrophages from PKCε−/− mice were deficient in the induction of nitric oxide synthase (NOS)-2, demonstrating a decrease in the activation of IκB kinase, a reduction in IκB degradation, and a decrease in nuclear factor (NF)κB nuclear translocation. After intravenous administration of Gram-negative or Gram-positive bacteria, PKCε−/− mice demonstrated a significantly decreased period of survival. This study provides direct evidence that PKCε is critically involved at an early stage of LPS-mediated signaling in activated macrophages. Furthermore, we demonstrate that in the absence of PKCε, host defense against bacterial infection is severely compromised, resulting in an increased incidence of mortality

It’s not what you do, it’s the way that you do it: An experimental task delineates among passive, reactive and interactive styles of behaviour on social networking sites

Studies have produced vastly disparate findings when exploring relationships between social networking site (SNS) usage and psychosocial well-being. These inconsistencies might reflect a lack of consideration for how people use SNS; specifically, while meaningful interactions are suggested to foster positive feelings, the passive consumption of others’ feeds is proposed to have negative effects on users’ well-being. To facilitate the empirical evaluation of these claims, the present study developed a computerised task to measure styles of usage on a mock SNS platform. Administering this Social Network Site Behaviour Task (SNSBT) online to 526 individuals, we identified three dissociable usage styles that extend the active-passive dichotomy employed frequently in the literature: passive use (consuming content posted by others), reactive use (reacting to others’ content), and interactive use (interacting with others through content sharing). Furthermore, our data reveal that these usage styles differ on several measures of psychosocial variables employed frequently in the disparate literature: more interactive users reported greater feelings of social connectedness and social capital than passive or reactive users. Importantly, however, our results also reveal the multi-dimensional nature of usage styles, with online network size and time spent on SNS platforms serving as potentially confounding influences on some psychosocial measures. These findings not only advance our understanding of SNS behaviour by providing empirical support for theoretic propositions, but also demonstrate the utility of the SNSBT for experimental investigations into the psychosocial outcomes of different SNS usage styles

Initial evidence for the criterion-related and structural validity of the long versions of the direct and meta-perspectives of the Coach-Athlete Relationship Questionnaire

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.The aim of the present study was to develop and initially validate a longer version of the direct (Jowett & Ntoumanis, 2004) and meta-perspectives (Jowett, 2009a, 2009b) of the Coach-Athlete Relationship Questionnaire (CART-Q). In Study 1, instruments (e.g. questionnaires, scales, and inventories) that have been used to assess relationship quality in the broader psychological literature were examined and items potentially relevant to the coach-athlete relationship were identified. The content validity of the identified items was then assessed using expert panels. A final questionnaire was subsequently prepared and administered to 693 participants (310 coaches and 383 athletes). Confirmatory factor analysis was employed to assess the multidimensional nature of the questionnaire based on the 3Cs (i.e. closeness, commitment, and complementarity) model of the coach-athlete relationship. The findings indicated that the direct and meta-perspective items of the long versions of the CART-Q approached an adequate data fit. Moreover, evidence for the internal consistency and criterion validity of the new instruments was also obtained. In Study 2, the newly developed measure was administered to an independent sample of 251 individuals (145 athletes and 106 coaches). Further statistical support was gained for the factorial validity and reliability of the longer version of the CART-Q

Relationships between the race implicit association test and other measures of implicit and explicit social cognition

Background: The race-based Implicit Association Test (IAT) was proposed to measure individual differences in implicit racial bias subsumed within social cognition. In recent years, researchers have debated the theoretical tenets underpinning the IAT, questioning whether performance on this task: (1) measures implicit attitudes that operate automatically outside of conscious awareness; (2) reflects individual differences in social cognition; and (3) can predict social behavior. One way to better address these research questions is to assess whether the race-IAT correlates with other implicit processes that are subsumed within social cognition. Aims: The current study assessed whether the race-IAT was related to other commonly used individual difference measures of implicit (and explicit) social cognition. Experiment 1 assessed whether dissociable patterns of performance on the race-IAT were related to measures of implicit imitative tendencies, emotion recognition and perspective taking toward White task actors, as well as explicit measures of trait and state affective empathy and racial bias. Overcoming limitations of task conceptual correspondence, Experiment 2 assessed whether these latter tasks were sensitive in detecting racial biases by using both White and Black task actors and again examined their relationships with the race-IAT. Method: In two lab-based experiments, 226 and 237 participants completed the race-IAT followed by an extensive battery of social cognition measures. Results: Across both experiments, pro-White/anti-Black bias on the race-IAT was positively related to a pro-White bias on explicit measures of positive affective empathy. However, relationships between the race-IAT and implicit imitative tendencies, perspective taking, emotion recognition, and explicit trait and negative state affective empathy were statistically equivalent. Conclusion: The race-IAT was consistently related to explicit measures of positive state affective empathy but not to other individual difference measures of implicit social cognition. These findings are discussed with regards to the theoretical underpinnings of the race-IAT as an individual difference measure of implicit social cognition, as well as alternative explanations relating to the reliability of social cognition measures and the various combinations of general-purpose (social and non-social) executive processes that underpin performance on these tasks

Deep characterization of human γδ T cell subsets defines shared and lineage-specific traits

Under non-pathological conditions, human γδ T cells represent a small fraction of CD3+ T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human γδ T cell subsets, Vδ1 and Vδ2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. We hypothesized that differences at the gene, phenotypic, and functional level would provide evidence that γδ T cell subpopulations belong to distinct lineages. Comparisons between each subset and the identification of the molecular determinants that underpin their differences has been hampered by experimental challenges in obtaining sufficient numbers of purified cells. By utilizing a stringent FACS-based isolation method, we compared highly purified human Vδ1 and Vδ2 cells in terms of phenotype, gene expression profile, and functional responses. We found distinct genetic and phenotypic signatures that define functional differences in γδ T cell populations. Differences in TCR components, repertoire, and responses to calcium-dependent pathways suggest that Vδ1 and Vδ2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vδ1 and Vδ2 cells in early immune responses

Quality of life changes after lumbar decompression in patients with tandem spinal stenosis

Objective Tandem spinal stenosis (TSS) is a degenerative spinal condition characterized by spinal canal narrowing at 2 or more distinct spinal levels. It is an aging-related condition that is likely to increase as the population ages, but which remains poorly described in the literature. Here we sought to determine the impact of primary lumbar decompression on quality-of-life (QOL) outcomes in patients with symptomatic TSS. Patients and methods We retrospectively reviewed 803 patients with clinical and radiographic evidence of TSS treated between 2008 and 2014 with a minimum 2-year follow-up. The records of patients with clinical and radiographic evidence of concurrent cervical and lumbar stenosis were reviewed. Prospectively gathered QOL data, including the Pain Disability Questionnaire (PDQ), Patient Health Questionnaire-9 (PHQ-9), EuroQOL-5 Dimensions (EQ-5D), and Visual Analogue Scale (VAS) for low back pain, were assessed at the 6-month, 1-year, and 2-year follow-ups. Results Of 803 identified patients (mean age 66.2 years; 46.9% male), 19.6% underwent lumbar decompression only, 14.1% underwent cervical + lumbar decompression, and 66.4% underwent conservative management only. Baseline VAS scores were similar across all groups, but patients undergoing conservative management had better baseline QOL scores on all other measures. Both surgical cohorts experienced significant improvements in the VAS, PDQ, and EQ-5D at all time points; patients in the cervical + lumbar cohort also had significant improvement in the PHQ-9. Conservatively managed patients showed no significant improvement in QOL scores at any follow-up interval. Conclusion Lumbar decompression with or without cervical decompression improves low back pain and QOL outcomes in patients with TSS. The decision to prioritize lumbar decompression is therefore unlikely to adversely affect long-term quality-of-life improvements

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses

Heterogeneous yet stable V delta 2((+)) T-cell profiles define distinct cytotoxic effector potentials in healthy human individuals

The Wellcome Trust [096954/Z/11/Z]; and Bloodwise; grant award 14026 (formally Leukaemia & Lymphoma Research)