Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study ...the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.
Current urban and district energy management systems lack a common semantic referential for effectively interrelating intelligent sensing, data models and energy models with visualization, analysis ...and decision support tools. This paper describes the structure, as well as the rationale that led to this structure, of an ontology that captures the real-world concepts of a district energy system, such as a district heating and cooling system. This ontology (called ee-district ontology) is intended to support knowledge provision that can play the role of an intermediate layer between high-level energy management software applications and local monitoring and control software components. In order to achieve that goal, the authors propose to encapsulate queries to the ontology in a scalable web service, which will facilitate the development of interfaces for third-party applications. Considering the size of the ee-district ontology once populated with data from a specific district case study, this could prove to be a repetitive and time-consuming task for the software developer. This paper therefore assesses the feasibility of ontology-driven automation of web service development that is to be a core element in the deployment of heterogeneous district-wide energy management software.
•The authors developed a methodology for the development of an ontology capturing the concepts of a district energy system.•An ontology of district energy systems has been implemented in OWL and instantiated for three real-world districts•The ontology supports district energy management software tools with regard to semantic knowledge and interoperability.•The ontology is hosted by a semantic repository and is linked via a web service generated using metaprogramming principles.
Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social ...difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.
The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The ...number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown.
This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs.
We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia.
Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI.
These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.
Background Although the prevalence of mental illness and behaviour problems is lower in adults with Down syndrome (DS) than in other populations with intellectual disabilities, they do present ...emotional and relational problems, as well as social integration difficulties. However, studies reporting on specific competences known to be central in developing appropriate social relationships (e.g. social reasoning, emotion processing, theory of mind) remain rare in the adult DS population and the mechanisms underlying these people's emotional and relational difficulties are unclear.
Method The present study investigated the ability to understand the appropriateness of others' social behaviour in 34 adults with DS, using the Social Resolution Task (SRT). Their results were compared with those of 34 typically developing (TD) children matched for gender and receptive vocabulary. The relationships among the SRT experimental task, cognitive competences (receptive and productive vocabulary, non‐verbal reasoning, inhibition, selective attention) and a caregiver‐rated measure of socio‐emotional behaviour were examined in the DS group.
Results The DS participants' global SRT scores did not differ from those of the controls. However, analyses of the SRT subscores revealed that the DS group identified significantly fewer inappropriate situations than the control group. Nevertheless, when they correctly identified the behaviour as inappropriate, they were as well as the controls to explain the rules underlying their responses. Regression analyses showed that receptive vocabulary and selective attention and a specific dimension of the socio‐emotional profile (social relating skills) constituted the best predictors of the DS adults' performance on the SRT.
Conclusions The main findings show that the DS participants demonstrate relatively good social reasoning skills in comparison with TD children matched for verbal age. However, the two groups present distinctions in their response patterns, and the influence of cognitive variables on success on the SRT also appears different. While selective attention skills are found to be significant predictors for both groups, the influence of receptive vocabulary level is much stronger in the DS group. The implications of particular cognitive and socio‐emotional factors for success on the SRT in this group are considered in more detail.
The present study proposed to test the applicability of a new emotional Stroop-like paradigm among 49 adults with Down syndrome (DS), matched with typically developing children on gender and ...receptive vocabulary. Stimuli with neutral and emotional content were presented in two identical computerized tasks. This experimental design allowed comparisons of inhibition performance according to the nature of the material. Main results showed that the DS group processed the emotional material more poorly than the control group in the inhibition condition, whereas all participants performed near or at ceiling in the control condition. Regarding the response latencies, both groups processed emotional material slower than the neutral material. The DS participants did not take more time to respond than their controls, but they presented a distinct response latency pattern during the task: while the control group kept their response times constant, the DS group showed an improvement during the task.
We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of ...bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism.
Individuals with Autism Spectrum Disorder (ASD) seem to have difficulties looking others in the eyes, but the substrate for this behavior is not well understood. The subcortical pathway, which ...consists of superior colliculus, pulvinar nucleus of the thalamus, and amygdala, enables rapid and automatic face processing. A specific component of this pathway - i.e., the amygdala - has been shown to be abnormally activated in paradigms where individuals had to specifically attend to the eye-region; however, a direct examination of the effect of manipulating the gaze to the eye-regions on all the components of the subcortical system altogether has never been performed. The subcortical system is particularly important as it shapes the functional specialization of the face-processing cortex during development. Using functional MRI, we investigated the effect of constraining gaze in the eye-region during dynamic emotional face perception in groups of participants with ASD and typical controls. We computed differences in activation in the subcortical face processing system (superior colliculus, pulvinar nucleus of the thalamus and amygdala) for the same stimuli seen freely or with the gaze constrained in the eye-region. Our results show that when constrained to look in the eyes, individuals with ASD show abnormally high activation in the subcortical system, which may be at the basis of their eye avoidance in daily life.
Numerous models have been developed to account for the complex properties of the random walks of biomolecules. However, when analysing experimental data, conditions are rarely met to ensure model ...identification. The dynamics may simultaneously be influenced by spatial and temporal heterogeneities of the environment, out-of-equilibrium fluxes and conformal changes of the tracked molecules. Recorded trajectories are often too short to reliably discern such multi-scale dynamics, which precludes unambiguous assessment of the type of random walk and its parameters. Furthermore, the motion of biomolecules may not be well described by a single, canonical random walk model. Here, we develop a two-step statistical testing scheme for comparing biomolecule dynamics observed in different experimental conditions without having to identify or make strong prior assumptions about the model generating the recorded random walks. We first train a graph neural network to perform simulation-based inference and thus learn a rich summary statistics vector describing individual trajectories. We then compare trajectories obtained in different biological conditions using a non-parametric maximum mean discrepancy (MMD) statistical test on their so-obtained summary statistics. This procedure allows us to characterise sets of random walks regardless of their generating models, without resorting to model-specific physical quantities or estimators. We first validate the relevance of our approach on numerically simulated trajectories. This demonstrates both the statistical power of the MMD test and the descriptive power of the learnt summary statistics compared to estimates of physical quantities. We then illustrate the ability of our framework to detect changes in α-synuclein dynamics at synapses in cultured cortical neurons, in response to membrane depolarisation, and show that detected differences are largely driven by increased protein mobility in the depolarised state, in agreement with previous findings. The method provides a means of interpreting the differences it detects in terms of single trajectory characteristics. Finally, we emphasise the interest of performing various comparisons to probe the heterogeneity of experimentally acquired datasets at different levels of granularity (e.g., biological replicates, fields of view, and organelles).
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