BACKGROUND:Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the "social brain," a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD. METHODS:As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits. RESULTS:We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders. CONCLUSIONS:Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition.
Contributors:Criswell, Katharine E, Gillis, J Andrew
The vertebral skeleton is a defining feature of vertebrate animals. However, the mode of vertebral segmentation varies considerably between major lineages. In tetrapods, adjacent somite halves recombine to form a single vertebra through the process of 'resegmentation'. In teleost fishes, there is considerable mixing between cells of the anterior and posterior somite halves, without clear resegmentation. To determine whether resegmentation is a tetrapod novelty, or an ancestral feature of jawed vertebrates, we tested the relationship between somites and vertebrae in a cartilaginous fish, the skate (Leucoraja erinacea). Using cell lineage tracing, we show that skate trunk vertebrae arise through tetrapod-like resegmentation, with anterior and posterior halves of each vertebra deriving from adjacent somites. We further show that tail vertebrae also arise through resegmentation, though with a duplication of the number of vertebrae per body segment. These findings resolve axial resegmentation as an ancestral feature of the jawed vertebrate body plan.
Contributors:Martinez, Jose, Sirri, Omar
This paper examines bakeries and checkpoints through their relationship to the state and connects considerations of affect with the burgeoning literature on infrastructure. Drawing on ethnographic fieldwork in Amman and Baghdad, we centre routine encounters at these sites, and argue that infrastructural engagements ignite energies, desires and sentiments that are deeply implicated in how the state plays out in everyday life. We zoom in on these ordinary affects and unpack the situated histories of rule in which they emerge. In Amman and Baghdad, stately affects work in and through infrastructure, doing so with regularity and intensity, and at specific times and places. The state effect transpires and thrives through these quotidian affective resonances, not just in the realm of ideas and imaginaries.
Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.
Contributors:Cadwallader, Lauren, Cronin, G, Hansen, D
In the second blog in our series marking the end of the Open Research Pilot (a two-year initiative involving University of Cambridge research groups, University Research Support, and Wellcome Trust’s Open Research Team), Dr Laurent Gatto tells us about his group’s involvement with the project. His particular Open interests during this time have been how to influence the research community in general towards greater openness.
All of the articles in this special issue show the necessity of having to combine different kinds of sources—texts with images, images with objects, and objects with absences—to build an integrated history of the material worlds of food in the early modern period. They also reflect newer approaches to materiality which are sensitive to the relationship between matter and the senses and consider the haptic, visual, olfactory, and even aural aspects of cooking and eating alongside taste. In turn, the tastes of collectors and the fragility and absence of source material also need to be taken into consideration in order to write a meaningful cultural and social history of food. Despite the ephemeral nature of eating and cooking, this special issue shows that the sources studied by historians of material culture of the early modern period are remarkably rich, and their analysis fruitful.