One step ahead: Investigating the influence of prior knowledge on the perception of others’ actions

Historically, a dominant view has been that we understand others by directly matching their actions to our own motor system, emphasising the importance of bottom-up processes during social perception. However, more recent theories suggest that instead we actively anticipate others actions based upon intentions inferred outside of the motor system, from social cues such as language, eye gaze and object information. Across 13 experiments, the established representational momentum paradigm, as well as a cross-modal visuotactile paradigm were employed to test the hypothesis that people’s perceptual processes while observing the actions of others would be affected by such top-down cues about the actor’s intentions. We found, first, that people overestimate other people’s actions in the direction of motion. Importantly, these overestimations were directly influenced by social cues. Saying or hearing a word congruent with a subsequently observed action resulted in the action being perceived as further along its trajectory. Second, we found that people anticipate the tactile outcomes of other people’s actions with their own sensory tactile systems but that the mechanisms differed for bottom-up and top-down driven predictions. In a task in which people had to detect tactile stimulation while watching others, seeing impending hand-object contact increased the bias to perceive tactile stimulation, even when there was none, while impending contact that could not be seen but only inferred increased tactile sensitivity. These findings are discussed in the context of recent theories of top-down predictive processing during social perception and from the perspective of multisensory integration

Putting Your Money Where Your Mouth is: Examining Metacognition in ASD Using Post-decision Wagering

It has been argued that metacognition and mindreading rely on the same cognitive processes (Carruthers in The opacity of mind: an integrative theory of self-knowledge, Oxford University Press, Oxford, 2011). It is widely accepted that mindreading is diminished among individuals diagnosed with autism (Brunsdon and Happé in Autism 18(1):17–30, 2014), however, little is known about metacognition. This study examined metacognition in relation to mindreading and autism using post-decision wagering. Results from a student sample showed negative associations between autism traits and metacognitive accuracy, and metacognitive reaction times and mindreading. These findings were replicated in a general population sample, providing evidence of a reliable association between metacognition, mindreading and autism traits. However, adults diagnosed with autism showed equivalent levels of metacognitive accuracy to age- and IQ-matched comparison participants, albeit only with an overall increase in meta-level processing time

Interoception is Impaired in Children, But Not Adults, with Autism Spectrum Disorder

Interoception (the ability to sense what’s going on inside one’s body) is considered integral to many higher-order cognitive processes. Some have speculated that impaired interoception may underpin some features of ASD. Yet, in Experiment 1, we found no evidence of a between-group difference in either cardiac or respiratory interoceptive accuracy among 21 adults with ASD and 21 matched controls. Bayesian analyses suggested the data strongly supported the null hypothesis. In Experiment 2, we measured cardiac interoceptive accuracy in 21 children with ASD and 21 matched controls. Here interoceptve accuracy was significantly diminished in the ASD group and was associated with a moderate-to-large effect size. Results suggest early interoception difficulties are resolved or compensated for by adulthood in people with ASD

Interoceptive impairments do not lie at the heart of autism or alexithymia

Quattrocki and Friston (2014) argued that abnormalities in interoception—the process of representing one’s internal physiological states—could lie at the heart of autism, because of the critical role interoception plays in the ontogeny of social-affective processes. This proposal drew criticism from proponents of the alexithymia hypothesis, who argue that social-affective and underlying interoceptive impairments are not a feature of autism per se, but of alexithymia (a condition characterized by difficulties describing and identifying one’s own emotions), which commonly co-occurs with autism. Despite the importance of this debate for our understanding of autism spectrum disorder (ASD), and of the role of interoceptive impairments in psychopathology, more generally, direct empirical evidence is scarce and inconsistent. Experiment 1 examined in a sample of 137 neurotypical (NT) individuals the association among autistic traits, alexithymia, and interoceptive accuracy (IA) on a standard heartbeat-tracking measure of IA. In Experiment 2, IA was assessed in 46 adults with ASD (27 of whom had clinically significant alexithymia) and 48 NT adults. Experiment 1 confirmed strong associations between autistic traits and alexithymia, but yielded no evidence to suggest that either was associated with interoceptive difficulties. Similarly, Experiment 2 provided no evidence for interoceptive impairments in autistic adults, irrespective of any co-occurring alexithymia. Bayesian analyses consistently supported the null hypothesis. The observations pose a significant challenge to notions that interoceptive impairments constitute a core feature of either ASD or alexithymia, at least as far as the direct perception of interoceptive signals is concerned

Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis

Aberrant expansion of KRT5+ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+ cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+ cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5+ cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+ cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche

Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection.

The metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma were characterized using multiplatform metabolic phenotyping with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Quantitative measurements of lipoprotein subfractions, α-1-acid glycoprotein, glucose, and biogenic amines were made on samples from symptomatic coronavirus disease 19 (COVID-19) patients who had tested positive for the SARS-CoV-2 virus (n = 17) and from age- and gender-matched controls (n = 25). Data were analyzed using an orthogonal-projections to latent structures (OPLS) method and used to construct an exceptionally strong (AUROC = 1) hybrid NMR-MS model that enabled detailed metabolic discrimination between the groups and their biochemical relationships. Key discriminant metabolites included markers of inflammation including elevated α-1-acid glycoprotein and an increased kynurenine/tryptophan ratio. There was also an abnormal lipoprotein, glucose, and amino acid signature consistent with diabetes and coronary artery disease (low total and HDL Apolipoprotein A1, low HDL triglycerides, high LDL and VLDL triglycerides), plus multiple highly significant amino acid markers of liver dysfunction (including the elevated glutamine/glutamate and Fischer's ratios) that present themselves as part of a distinct SARS-CoV-2 infection pattern. A multivariate training-test set model was validated using independent samples from additional SARS-CoV-2 positive patients and controls. The predictive model showed a sensitivity of 100% for SARS-CoV-2 positivity. The breadth of the disturbed pathways indicates a systemic signature of SARS-CoV-2 positivity that includes elements of liver dysfunction, dyslipidemia, diabetes, and coronary heart disease risk that are consistent with recent reports that COVID-19 is a systemic disease affecting multiple organs and systems. Metabolights study reference: MTBLS2014

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Mechanistic evaluation of panretinal photocoagulation versus aflibercept in proliferative diabetic retinopathy: CLARITY substudy

Purpose: The purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy. Methods: This is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA). Results: The AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, −0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45). Conclusions: Intravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks

Transacylation and hydrolysis of the acyl glucuronides of ibuprofen and its α-methyl-substituted analogues investigated by ¹H NMR spectroscopy and computational chemistry: Implications for drug design.

Drugs and drug metabolites containing a carboxylic-acid moiety can undergo in vivo conjugation to form 1-β-O-acyl-glucuronides (1-β-O-AGs). In addition to hydrolysis, these conjugates can undergo spontaneous acyl migration, and anomerisation reactions, resulting in a range of positional isomers. Facile transacylation has been suggested as a mechanism contributing to the toxicity of acyl glucuronides, with the kinetics of these processes thought to be a factor. Previous 1H NMR spectroscopic and HPLC-MS studies have been conducted to measure the degradation rates of the 1-β-O-AGs of three nonsteroidal anti-inflammatory drugs (ibufenac, R-ibuprofen, S-ibuprofen) and a dimethyl-analogue (termed here as "bibuprofen"). These studies have also determined the relative contributions of hydrolysis and acyl migration in both buffered aqueous solution, and human plasma. Here, a detailed kinetic analysis is reported, providing the individual rate constants for the acyl migration and hydrolysis reactions observed in buffer for each of the 4 AGs, together with the overall degradation rate constants of the parent 1-β-O-AGs. Computational modelling of the reactants and transition states of the transacylation reaction using density functional theory indicated differences in the activation energies that reflected the influence of both substitution and stereochemistry on the rate of transacylation/hydrolysis