Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Growth and morphology of 0.80eV photoemitting indium nitride nanowires

InN nanowires with high efficiency photoluminescence emission at 0.80 eV are reported for the first time. InN nanowires were synthesized via a vapor solid growth mechanism from high purity indium metal and ammonia. The products consist of only hexagonal wurtzite phase InN. Scanning electron microscopy showed wires with diameters of 50-100nm and having fairly smooth morphologies. High-resolution transmission electron microscopy revealed high quality, single crystal InN nanowires which grew in the <0001> direction. The group-III nitrides have become an extremely important technological material over the past decade. They are commonly used in optoelectronic devices, such as high brightness light-emitting diodes (LEDs) and low wavelength laser diodes (LDs), as well as high power/high frequency electronic devices. Recently InN thin films grown by MOCVD and MBE were found to have a bandgap energy in the range of 0.7-0.9 eV, much lower than the value of {approx}1.9 eV found for InN films grown by sputtering. This large decrease in the direct bandgap transition energy and the ability to form ternary (InGaN) and quaternary (AlInGaN) alloys increases the versatility of group-III nitride optoelectronic devices, ranging from the near IR to the UV. Additionally, InN has some promising transport and electronic properties. It has the smallest effective electron mass of all the group-III nitrides which leads to high mobility and high saturation velocity10 and a large drift velocity at room temperature. As a result of these unique properties, there has been a large increase in interest in InN for potential use in optoelectronic devices, such as LDs and high efficiency solar cells, as well as high frequency/high power electronic devices

A meta-analysis of gene expression signatures of blood pressure and hypertension

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.Tianxiao Huan, Tõnu Esko, Marjolein J. Peters, Luke C. Pilling, Katharina Schramm, Claudia Schurmann, Brian H. Chen, Chunyu Liu, Roby Joehanes, Andrew D. Johnson, Chen Yao, Sai-xia Ying, Paul Courchesne, Lili Milani, Nalini Raghavachari, Richard Wang, Poching Liu, Eva Reinmaa, Abbas Dehghan, Albert Hofman, André G. Uitterlinden, Dena G. Hernandez, Stefania Bandinelli, Andrew Singleton, David Melzer, Andres Metspalu, Maren Carstensen, Harald Grallert, Christian Herder, Thomas Meitinger, Annette Peters, Michael Roden, Melanie Waldenberger, Marcus Dörr, Stephan B. Felix, Tanja Zeller, International Consortium for Blood Pressure GWAS, ICBP, Ramachandran Vasan, Christopher J. O'Donnell, Peter J. Munson, Xia Yang, Holger Prokisch, Uwe Völker, Joyce B. J. van Meurs, Luigi Ferrucci, Daniel Lev

P300 and uncertainty reduction in a concept identification task.

The relationship between the amplitude of P300, the mean amplitude of the Slow Wave, and uncertainty reduction after (dis)confirmation of hypotheses was studied in a Concept-Identification task. The subjects had to categorize stimuli according to a conceptual rule (joint denial or exclusion) and to rate the confidence that their classification was correct. Three types of feedback were distinguished: confirming (subject's categorization was correct), disconfirming (subject's categorization was incorrect), and non-informative feedback. The EEG was averaged separately according to the three types of feedback and the two confidence ratings (low, high). The data showed the predicted interaction between type of feedback and confidence level. A larger P300 amplitude turned up after confirming feedback when the subject was less confident, than when he was more confident. The reverse was found after disconfirming feedback. The P300 amplitude after non-informative feedback was not influenced by confidence. The mean amplitude of the Slow Wave showed approximately the same interaction pattern. The results were interpreted in terms of changes in the probability of hypotheses which subjects use to categorize stimuli in a Concept-Identification task

Attentional differences in a driving hazard perception task in adults with autism spectrum disorders

The current study explored attentional processing of social and non social stimuli in ASD within the context of a driving hazard perception task. Participants watched videos of road scenes and detected hazards while their eye movements were recorded. Although individuals with ASD demonstrated relatively good detection of driving hazards, they were slower to orient to hazards. Greater attentional capture in the time preceding the hazards’ onset was associated with lower verbal IQ. The findings suggest that individuals with ASD may distribute and direct their attention diferently when identifying driving hazards

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

ANS: Aberrant Neurodevelopment of the Social Cognition Network in Adolescents with Autism Spectrum Disorders

Background: Autism spectrum disorders (ASD) are characterized by aberrant neurodevelopment. Although the ASD brain undergoes precocious growth followed by decelerated maturation during early postnatal period of childhood, the neuroimaging approach has not been empirically applied to investigate how the ASD brain develops during adolescence. Methodology/Principal Findings: We enrolled 25 male adolescents with high functioning ASD and 25 typically developing controls for voxel-based morphometric analysis of structural magnetic resonance image. Results indicate that there is an imbalance of regional gray matter volumes and concentrations along with no global brain enlargement in adolescents with high functioning ASD relative to controls. Notably, the right inferior parietal lobule, a role in social cognition, have a significant interaction of age by groups as indicated by absence of an age-related gain of regional gray matter volume and concentration for neurodevelopmental maturation during adolescence. Conclusions/Significance: The findings indicate the neural correlates of social cognition exhibits aberrant neurodevelopment during adolescence in ASD, which may cast some light on the brain growth dysregulation hypothesis. The period of abnormal brain growth during adolescence may be characteristic of ASD. Age effects must be taken into account while measures of structural neuroimaging have been clinically put forward as potential phenotypes for ASD