Observational learning of atypical biological kinematics in autism

Observing and voluntarily imitating the biological kinematics displayed by a model underpins the acquisition of new motor skills via sensorimotor processes linking perception with action. Differences in voluntary imitation in autism could be related to sensorimotor processing activity during action-observation of biological motion, as well as how sensorimotor integration processing occurs across imitation attempts. Using an observational practice protocol, which minimized the active contribution of the peripheral sensorimotor system, we examined the contribution of sensorimotor processing during action-observation. The data showed that autistic participants imitated both the temporal duration and atypical kinematic profile of the observed movement with a similar level of accuracy as neurotypical participants. These findings suggest the lower-level perception-action processes responsible for encoding biological kinematics during the action-observation phase of imitation are operational in autism. As there was no task-specific engagement of the peripheral sensorimotor system during observational practice, imitation difficulties in autism are most likely underpinned by sensorimotor integration issues related to the processing of efferent and (re)afferent sensorimotor information during trial-to-trial motor execution

Ranking metabolite sets by their activity levels

Related metabolites can be grouped into sets in many ways, e.g., by their participation in series of chemical reactions (forming metabolic pathways), or based on fragmentation spectral similarities or shared chemical substructures. Understanding how such metabolite sets change in relation to experimental factors can be incredibly useful in the interpretation and understanding of complex metabolomics data sets. However, many of the available tools that are used to perform this analysis are not entirely suitable for the analysis of untargeted metabolomics measurements. Here, we present PALS (Pathway Activity Level Scoring), a Python library, command line tool, and Web application that performs the ranking of significantly changing metabolite sets over different experimental conditions. The main algorithm in PALS is based on the pathway level analysis of gene expression (PLAGE) factorisation method and is denoted as mPLAGE (PLAGE for metabolomics). As an example of an application, PALS is used to analyse metabolites grouped as metabolic pathways and by shared tandem mass spectrometry fragmentation patterns. A comparison of mPLAGE with two other commonly used methods (overrepresentation analysis (ORA) and gene set enrichment analysis (GSEA)) is also given and reveals that mPLAGE is more robust to missing features and noisy data than the alternatives. As further examples, PALS is also applied to human African trypanosomiasis, Rhamnaceae, and American Gut Project data. In addition, normalisation can have a significant impact on pathway analysis results, and PALS offers a framework to further investigate this. PALS is freely available from our project Web site

Associations between paratuberculosis ELISA results and test-day records of cows enrolled in the Irish Johne's Disease Control Program

peer-reviewedThe effect of the Mycobacterium avium ssp. paratuberculosis (MAP) ELISA status on test-day milk performance of cows from Irish herds enrolled in the pilot national voluntary Johne's disease control program during 2013 to 2015 was estimated. A data set comprising 92,854 cows and 592,623 complete test-day records distributed across 1,700 herds was used in this study. The resulting ELISA outcome (negative, inconclusive, and positive) of each cow within each year of the program was used to allocate the cow into different scenarios representing the MAP status. At MAPscenario1, all cows testing ELISA nonnegative (i.e., inconclusive and positive) were assigned a MAP-positive status; at MAPscenario2 only cows testing ELISA-positive were assigned a MAP-positive status; at MAPscenario3 only cows testing ELISA nonnegative (inconclusive or positive) and gathered exclusively from herds where at least 2 further ELISA nonnegative (inconclusive or positive) cows were found were assigned a MAP-positive status; at MAPscenario4 only cows testing ELISA-positive that were gathered exclusively from herds where at least 2 further ELISA-positive cows were found were assigned a MAP-positive status. Milk outputs based on test-day records were standardized for fat and protein contents (SMY) and the effect of MAP ELISA status on the SMY was estimated by a linear mixed effects model structure. The SMY mean difference recorded at test day between cows with a MAP-positive status and those with a MAP-negative status within MAPscenario1 was estimated at −0.182 kg/test day; the mean difference was −0.297 kg/test day for MAPscenario2; for MAPscenario3 mean difference between MAP-positive status and MAP test-negative cows was −0.209 kg/test day, and for MAPscenario4, the difference was −0.326 kg/test day.This study was carried out as part of the ICONMAP (Improved Control of Mycobacterium avium ssp. paratuberculosis) multidisciplinary research program, funded by the Research Stimulus Fund 2011, administered by the Irish Department of Agriculture, Food and the Marine

Monolayer and Bilayer Perfluoropentacene on Cu(111)

Perfluoropentacene (PFP), an n-type organic semiconductor, is deposited at monolayer and bilayer coverages on Cu(111). Scanning tunneling microscopy at various bias voltages is used to investigate the geometric and electronic structures of the layer. The appearances of the first layer and second layer differ, likely due to perturbation of the first layer electronic structure by the substrate. This has been previously observed for pentacene (Pn), the isostructural p-type organic semiconductor. The PFP film has a unit cell of (4, −3,3 4) relative to the substrate, which is larger than that of Pn/Cu(111), representing a half-integer increment in each direction

Reward System Dysfunction as a Neural Substrate of Symptom Expression Across the General Population and Patients With Schizophrenia

Dysfunctional patterns of activation in brain reward networks have been suggested as a core element in the pathophysiology of schizophrenia. However, it remains unclear whether this dysfunction is specific to schizophrenia or can be continuously observed across persons with different levels of nonclinical and clinical symptom expression. Therefore, we sought to investigate whether the pattern of reward system dysfunction is consistent with a dimensional or categorical model of psychosis-like symptom expression. 23 patients with schizophrenia and 37 healthy control participants with varying levels of psychosis-like symptoms, separated into 3 groups of low, medium, and high symptom expression underwent event-related functional magnetic resonance imaging while performing a Cued Reinforcement Reaction Time task. We observed lower activation in the ventral striatum during the expectation of high vs no reward to be associated with higher symptom expression across all participants. No significant difference between patients with schizophrenia and healthy participants with high symptom expression was found. However, connectivity between the ventral striatum and the medial orbitofrontal cortex was specifically reduced in patients with schizophrenia. Dysfunctional local activation of the ventral striatum depends less on diagnostic category than on the degree of symptom expression, therefore showing a pattern consistent with a psychosis continuum. In contrast, aberrant connectivity in the reward system is specific to patients with schizophrenia, thereby supporting a categorical view. Thus, the results of the present study provide evidence for both continuous and discontinuous neural substrates of symptom expression across patients with schizophrenia and the general populatio

Pneumocystis pneumonia, a COVID-19 mimic, reminds us of the importance of HIV testing in COVID-19

While clinical environments are highly focused on COVID-19, reports of missed or delayed treatment for conditions that imitate COVID-19, such as pneumonia caused by the fungus Pneumocystis jirovecii, are emerging. Given the uncertain spectrum of COVID-19 presentations and variable sensitivity of laboratory tests for SARS-CoV-2, there is a risk that, without a high index of suspicion, alternative aetiologies may be overlooked while pursuing a diagnosis of COVID-19. The British HIV Association has been calling for the inclusion of HIV testing in all patients admitted to hospital with suspected COVID-19. In this article we reflect on the importance of including HIV testing to prevent avoidable morbidity and mortality in our patients.Publisher PDFPeer reviewe

Impaired Cross-Talk between Mesolimbic Food Reward Processing and Metabolic Signaling Predicts Body Mass Index

The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum in participants with a broad BMI spectrum. The study differentiated between general (i.e. monetary) and food related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m²) over a normal (20 to 25 kg/m²) and overweight (25 to 30 kg/m²) BMI, to class I (30 to 35 kg/m² ) and class II (35 to 40 kg/m²) obesity. A total of 24 participants underwent functional magnetic resonance imaging whilst performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn snack points or money coins which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the ventral striatum, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime). This relation was found to be mediated by impaired hormonal satiety signaling, i.e. increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling

Genomic RNA folding mediates assembly of human parechovirus

Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets.Peer reviewe