Interleukin-10 Mediated Autoregulation of Murine B-1 B-Cells and Its Role in Borrelia hermsii Infection

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-κB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10−/− mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B-1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity

First evidence for a massive extinction event affecting bees close to the K-T boundary

Bees and eudicot plants both arose in the mid-late Cretaceous, and their co-evolutionary relationships have often been assumed as an important element in the rise of flowering plants. Given the near-complete dependence of bees on eudicots we would expect that major extinction events affecting the latter would have also impacted bees. However, given the very patchy distribution of bees in the fossil record, identifying any such extinctions using fossils is very problematic. Here we use molecular phylogenetic analyses to show that one bee group, the Xylocopinae, originated in the mid-Cretaceous, coinciding with the early radiation of the eudicots. Lineage through time analyses for this bee subfamily show very early diversification, followed by a long period of seemingly no radiation and then followed by rapid diversification in each of the four constituent tribes. These patterns are consistent with both a long-fuse model of radiation and a massive extinction event close to the K-T boundary. We argue that massive extinction is much more plausible than a long fuse, given the historical biogeography of these bees and the diversity of ecological niches that they occupy. Our results suggest that events near the K-T boundary would have disrupted many plant-bee relationships, with major consequences for the subsequent evolution of eudicots and their pollinators.Sandra M. Rehan, Remko Leys, Michael P. Schwar

Shared and Disorder-Specific Event-Related Brain Oscillatory Markers of Attentional Dysfunction in ADHD and Bipolar Disorder.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) often present with overlapping symptoms and cognitive impairments, such as increased fluctuations in attentional performance measured by increased reaction-time variability (RTV). We previously provided initial evidence of shared and distinct event-related potential (ERP) impairments in ADHD and BD in a direct electrophysiological comparison, but no study to date has compared neural mechanisms underlying attentional impairments with finer-grained brain oscillatory markers. Here, we aimed to compare the neural underpinnings of impaired attentional processes in ADHD and BD, by examining event-related brain oscillations during a reaction-time task under slow-unrewarded baseline and fast-incentive conditions. We measured cognitive performance, ERPs and brain-oscillatory modulations of power and phase variability in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. Compared to controls, both ADHD and BD groups showed increased RTV in the baseline condition and increased RTV, theta phase variability and lower contingent negative variation in the fast-incentive condition. Unlike controls, neither clinical group showed an improvement from the slow-unrewarded baseline to the fast-incentive condition in attentional P3 amplitude or alpha power suppression. Most impairments did not differ between the disorders, as only an adjustment in beta suppression between conditions (lower in the ADHD group) distinguished between the clinical groups. These findings suggest shared impairments in women with ADHD and BD in cognitive and neural variability, preparatory activity and inability to adjust attention allocation and activation. These overlapping impairments may represent shared neurobiological mechanisms of attentional dysfunction in ADHD and BD, and potentially underlie common symptoms in both disorders.We thank all who made this research possible: The National Adult ADHD Clinic at the South London and Maudsley Hospital, Dr Helen Costello, Prof Sophia Frangou, Prof Anne Farmer, Jessica Deadman, Hannah Collyer, Sarah-Jane Gregori, and all participants who contributed their time to the study. Dr Giorgia Michelini was supported by a 1+3 PhD studentship awarded by the MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London (G9817803). This project was supported by an Economic and Social Research Council studentship to Dr Viryanaga Kitsune (ES/100971X/1). Dr Giorgia Michelini and Prof Philip Asherson are supported by generous grants from the National Institute for Health Research Biomedical Research Centre for Mental Health at King’s College London, Institute of Psychiatry, Psychology and Neuroscience and South London and Maudsley National Health Service (NHS) Foundation Trust. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Empirical investigation of the temporal relations between speech and facial expressions of emotion

Lien vers l'article original : http://link.springer.com/article/10.1007/s12193-010-0050-4Behavior models implemented within Embodied Conversational Agents (ECAs) require nonverbal communication to be tightly coordinated with speech. In this paper we present an empirical study seeking to explore the influence of the temporal coordination between speech and facial expressions of emotions on the perception of these emotions by users (measuring their performance in this task, the perceived realism of behavior, and user preferences).We generated five different conditions of temporal coordination between facial expression and speech: facial expression displayed before a speech utterance, at the beginning of the utterance, throughout, at the end of, or following the utterance. 23 subjects participated in the experiment and saw these 5 conditions applied to the display of 6 emotions (fear, joy, anger, disgust, surprise and sadness). Subjects recognized emotions most efficiently when facial expressions were displayed at the end of the spoken sentence. However, the combination users viewed as most realistic, preferred over others, was the display of the facial expression throughout speech utterance. We review existing literature to position our work and discuss the relationship between realism and communication performance. We also provide animation guidelines and draw some avenues for future work

Protect-me: a parallel-group, triple blinded, placebo-controlled randomised clinical trial protocol assessing antenatal maternal melatonin supplementation for fetal neuroprotection in early-onset fetal growth restriction

INTRODUCTION: Fetal growth restriction (FGR) is a serious pregnancy complication, associated with increased rates of perinatal death and morbidity among survivors. Most commonly FGR results from placental insufficiency, where the placenta fails to deliver the oxygen and nutrients required for normal fetal growth. This leads to fetal oxidative stress, resulting in organ damage through lipid peroxidation. The early developing brain is particularly susceptible, such that FGR is associated with poorer neurodevelopment, witnessed as cognitive and behavioural dysfunction, and cerebral palsy. Promisingly, melatonin, a lipid soluble antioxidant is neuroprotective in animal models of FGR. We present a protocol outlining a randomised, placebo-controlled trial to explore whether antenatal maternal melatonin supplementation in pregnancies with severe, early-onset FGR can improve neurodevelopment among survivors at 2 years of age. METHODS AND ANALYSES: We will recruit 336 women with a singleton pregnancy complicated by FGR between 23+0 and 31+6 weeks gestation. Participants will be randomised, stratified by gestational age, to either 30 mg melatonin per day or a visually identical placebo, continued until birth. Measures of maternal and fetal health will be collected until birth. Timing of birth will be determined by the treating clinical team in discussion with the woman. Neonatal and infant neurodevelopmental assessments will be undertaken, consisting of brain MRI at term corrected age, general movements assessment at term and 3 months' corrected age, and Bayley Scales of Infant & Toddler Development-III and Infant Toddler Social Emotional Assessment at 2.5 years corrected age. Analyses will be on intention to treat. The primary outcome is a difference of 5 points in the cognitive domain of the Bayley-III. Secondary outcomes address maternal and fetal safety. ETHICS AND DISSEMINATION: This trial has Monash Health Human Research and Ethics committee approval (17-0000-583A). Findings will be disseminated through peer-reviewed publications, conference presentations and to participants. TRIAL REGISTRATION NUMBER: ACTRN12617001515381; Pre-results