The female protective effect in autism spectrum disorder is not mediated by a single genetic locus

Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis. Methods: To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. Results: No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect. Conclusions: The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE.Intellectual and Developmental Disabilities Research Center at Washington University (NIH/NICHD) [P30 HD062171]; Simons Foundation (SFARI) [307705]; Canadian Institutes of Health Research; [R01 HD042541]SCI(E)[email protected]; [email protected]

Socially assistive robotics for post-stroke rehabilitation

BACKGROUND: Although there is a great deal of success in rehabilitative robotics applied to patient recovery post stroke, most of the research to date has dealt with providing physical assistance. However, new rehabilitation studies support the theory that not all therapy need be hands-on. We describe a new area, called socially assistive robotics, that focuses on non-contact patient/user assistance. We demonstrate the approach with an implemented and tested post-stroke recovery robot and discuss its potential for effectiveness. RESULTS: We describe a pilot study involving an autonomous assistive mobile robot that aids stroke patient rehabilitation by providing monitoring, encouragement, and reminders. The robot navigates autonomously, monitors the patient's arm activity, and helps the patient remember to follow a rehabilitation program. We also show preliminary results from a follow-up study that focused on the role of robot physical embodiment in a rehabilitation context. CONCLUSION: We outline and discuss future experimental designs and factors toward the development of effective socially assistive post-stroke rehabilitation robots

De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR= 1.6; 95% CI= 1.0-2.7; p= 0.03), are more common in female probands (p= 0.02), are enriched among genes encoding FMRP targets (p= 6× 10-9), and arise predominantly on the paternal chromosome (p< 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release

Can Machines Think? Interaction and Perspective Taking with Robots Investigated via fMRI

Krach S, Hegel F, Wrede B, Sagerer G, Binkofski F, Kircher T. Can Machines Think? Interaction and Perspective Taking with Robots Investigated via fMRI. PLoS ONE. 2008;3(7): e2597.Background When our PC goes on strike again we tend to curse it as if it were a human being. Why and under which circumstances do we attribute human-like properties to machines? Although humans increasingly interact directly with machines it remains unclear whether humans implicitly attribute intentions to them and, if so, whether such interactions resemble human-human interactions on a neural level. In social cognitive neuroscience the ability to attribute intentions and desires to others is being referred to as having a Theory of Mind (ToM). With the present study we investigated whether an increase of human-likeness of interaction partners modulates the participants' ToM associated cortical activity. Methodology/Principal Findings By means of functional magnetic resonance imaging (subjects n = 20) we investigated cortical activity modulation during highly interactive human-robot game. Increasing degrees of human-likeness for the game partner were introduced by means of a computer partner, a functional robot, an anthropomorphic robot and a human partner. The classical iterated prisoner's dilemma game was applied as experimental task which allowed for an implicit detection of ToM associated cortical activity. During the experiment participants always played against a random sequence unknowingly to them. Irrespective of the surmised interaction partners' responses participants indicated having experienced more fun and competition in the interaction with increasing human-like features of their partners. Parametric modulation of the functional imaging data revealed a highly significant linear increase of cortical activity in the medial frontal cortex as well as in the right temporo-parietal junction in correspondence with the increase of human-likeness of the interaction partner (computer<functional robot<anthropomorphic robot<human). Conclusions/Significance Both regions correlating with the degree of human-likeness, the medial frontal cortex and the right temporo-parietal junction, have been associated with Theory-of-Mind. The results demonstrate that the tendency to build a model of another's mind linearly increases with its perceived human-likeness. Moreover, the present data provides first evidence of a contribution of higher human cognitive functions such as ToM in direct interactions with artificial robots. Our results shed light on the long-lasting psychological and philosophical debate regarding human-machine interaction and the question of what makes humans being perceived as human

Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM

RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer’s disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor tyrosine-based activation motif (ITAM). SYK interacts with the Fc receptor by binding to doubly phosphorylated ITAM (p-ITAM) via its two tandem SH2 domains (SYK-tSH2). Interaction of the FCER1G p-ITAM with SYK-tSH2 enables SYK activation via phosphorylation. Since SYK activation is reported to exacerbate AD pathology, we hypothesized that disruption of this interaction would be beneficial for AD patients. Herein, we developed biochemical and biophysical assays to enable the discovery of small molecules that perturb the interaction between the FCER1G p-ITAM and SYKtSH2. We identified two distinct chemotypes using a high-throughput screen (HTS) and orthogonally assessed their binding. Both chemotypes covalently modify SYK-tSH2 and inhibit its interaction with FCER1G p-ITAM, however, these compounds lack selectivity and this limits their utility as chemical tools

M.J.: Encouraging physical therapy compliance with a hands-off mobile robot

This paper presents results toward our ongoing research program into hands-off assistive human-robot interaction [6]. Our work has focused on applications of socially assistive robotics in health care and education, where human supervision can be significantly augmented and complemented by intelligent machines. In this paper, we focus on the role of embodiment, empirically addressing the question: “In what ways can the robot’s physical embodiment be used effectively to positively influence human task-related behavior?” We hypothesized that users ’ personalities would correlate with their preferences of robot behavior expression. To test this hypothesis, we implemented an autonomous mobile robot aimed at the role of a monitoring and encouragement system for stroke patient rehabilitation. We performed a pilot study that indicates that the presence and behavior of the robot can influence how well people comply with their physical therapy. Categories and Subject Descriptors K.4.2 [Computers and Society]: social issues; J.4 [Socia

The female protective effect in autism spectrum disorder is not mediated by a single genetic locus

© 2015 Gockley et al.; licensee BioMed Central.Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part o

The female protective effect in autism spectrum disorder is not mediated by a single genetic locus

© 2015 Gockley et al.; licensee BioMed Central.Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part o

Robot-supported pointing interaction for intelligent environments

A natural interaction with appliances in smart environment is a highly desired form of controlling the surroundings using intuitively learned interpersonal means of communication. Hand and arm gestures, recognized by depth cameras, are a popular representative of this interaction paradigm. However they usually require stationary units that limit applicability in larger environments. To overcome this problem we are introducing a self-localizing mobile robot system that autonomously follows the user in the environment, in order to recognize performed gestures independent from the current user position. We have realized a prototypical implementation using a custom robot platform and evaluated the system with various users