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

Scanpath analysis of expertise and culture in teacher gaze in real-world classrooms

Humans are born to learn by understanding where adults look. This is likely to extend into the classroom, making teacher gaze an important topic for study. Expert teacher gaze has mainly been investigated in the laboratory, and has focused mostly on one cognitive process: teacher attentional (i.e., information-seeking) gaze. No known research has made direct cultural comparisons of teacher gaze or successfully found expert–novice differences outside Western settings. Accordingly, we conducted a real-world study of expert teacher gaze across two cultural settings, exploring communicative (i.e., information-giving) as well as attentional gaze. Forty secondary school teachers wore eye-tracking glasses, with 20 teachers (10 expert; 10 novice) from the UK and 20 teachers (10 expert; 10 novice) from Hong Kong. We used a novel eye-tracking scanpath analysis to ascertain the importance of expertise and culture, individually and as a combination. Attentional teacher scanpaths were significantly more similar within than across expertise and expertise + culture sub-groups; communicative scanpaths were significantly more similar within than across expertise and culture. Detailed analysis suggests that (1) expert teachers refer back to students constantly through focused gaze during both attentional and communicative gaze and that (2) expert teachers in Hong Kong scan students more than experts do in the UK

Multimodel assessment of the factors driving stratospheric ozone evolution over the 21st century

The evolution of stratospheric ozone from 1960 to 2100 is examined in simulations from 14 chemistry‐climate models, driven by prescribed levels of halogens and greenhouse gases. There is general agreement among the models that total column ozone reached a minimum around year 2000 at all latitudes, projected to be followed by an increase over the first half of the 21st century. In the second half of the 21st century, ozone is projected to continue increasing, level off, or even decrease depending on the latitude. Separation into partial columns above and below 20 hPa reveals that these latitudinal differences are almost completely caused by differences in the model projections of ozone in the lower stratosphere. At all latitudes, upper stratospheric ozone increases throughout the 21st century and is projected to return to 1960 levels well before the end of the century, although there is a spread among models in the dates that ozone returns to specific historical values. We find decreasing halogens and declining upper atmospheric temperatures, driven by increasing greenhouse gases, contribute almost equally to increases in upper stratospheric ozone. In the tropical lower stratosphere, an increase in upwelling causes a steady decrease in ozone through the 21st century, and total column ozone does not return to 1960 levels in most of the models. In contrast, lower stratospheric and total column ozone in middle and high latitudes increases during the 21st century, returning to 1960 levels well before the end of the century in most models

Review of the formulation of present-generation stratospheric chemistry-climate models and associated external forcings

The goal of the Chemistry‐Climate Model Validation (CCMVal) activity is to improve understanding of chemistry‐climate models (CCMs) through process‐oriented evaluation and to provide reliable projections of stratospheric ozone and its impact on climate. An appreciation of the details of model formulations is essential for understanding how models respond to the changing external forcings of greenhouse gases and ozonedepleting substances, and hence for understanding the ozone and climate forecasts produced by the models participating in this activity. Here we introduce and review the models used for the second round (CCMVal‐2) of this intercomparison, regarding the implementation of chemical, transport, radiative, and dynamical processes in these models. In particular, we review the advantages and problems associated with approaches used to model processes of relevance to stratospheric dynamics and chemistry. Furthermore, we state the definitions of the reference simulations performed, and describe the forcing data used in these simulations. We identify some developments in chemistry‐climate modeling that make models more physically based or more comprehensive, including the introduction of an interactive ocean, online photolysis, troposphere‐stratosphere chemistry, and non‐orographic gravity‐wave deposition as linked to tropospheric convection. The relatively new developments indicate that stratospheric CCM modeling is becoming more consistent with our physically based understanding of the atmosphere

Exposure to delayed visual feedback of the hand changes motor-sensory synchrony perception

We examined whether the brain can adapt to temporal delays between a self-initiated action and the naturalistic visual feedback of that action. During an exposure phase, participants tapped with their index finger while seeing their own hand in real time (~0 ms delay) or delayed at 40, 80, or 120 ms. Following exposure, participants were tested with a simultaneity judgment (SJ) task in which they judged whether the video of their hand was synchronous or asynchronous with respect to their finger taps. The locations of the seen and the real hand were either different (Experiment 1) or aligned (Experiment 2). In both cases, the point of subjective simultaneity (PSS) was uniformly shifted in the direction of the exposure lags while sensitivity to visual-motor asynchrony decreased with longer exposure delays. These findings demonstrate that the brain is quite flexible in adjusting the timing relation between a motor action and the otherwise naturalistic visual feedback that this action engenders

Why are anopheline mosquitoes not present in the Seychelles?

<p>Abstract</p> <p>Background</p> <p>Species of anopheline mosquitoes are largely distributed over emerged lands around the world and, within the tropics, few areas are without these insects, which are vectors of malaria parasites. Among the exceptions is the Seychelles archipelago in the western Indian Ocean. However, in the Aldabra island group, located in the extreme western portion of the archipelago, <it>Anopheles gambiae s.l. </it>was introduced, leading to massive proliferation and then elimination, with the most recent autochthonous malaria cases recorded in 1931.</p> <p>Methods</p> <p>In order to re-examine the absence of anopheline mosquitoes in the Seychelles, an entomological field survey was conducted in December 2008 at 17 sites on four granitic islands, including Mahé and Praslin, and ten sites on coralline atolls in the extreme west, including Aldabra.</p> <p>Results</p> <p>No evidence of larval or adult anophelines was found at the surveyed sites, which supports their absence in the Seychelles.</p> <p>Conclusions</p> <p>In the granitic islands of the Seychelles, the climate is favourable for anophelines. However, these islands are protected by their remoteness and prevailing seasonal winds. In addition, stagnant freshwater, required in anopheline larval development, is relatively uncommon on the granitic islands because of the steep slopes. In the southwestern atolls (Aldabra and Providence-Farquhar groups), the presence of a long dry season of up to nine months and the total absence of permanent natural freshwater prevents the breeding of anophelines and their successful colonization. The Seychelles does not have any native land mammals and like in other parts of the world (Antarctica, Iceland, New Caledonia, Central Pacific islands) their absence is associated with the lack of anophelines. This suggests an obligatory relationship for anophelines to feed on terrestrial mammals, without alternative for blood-feeding sources, such as bats, birds and reptiles.</p

Angiopoietin-1 enhances neutrophil chemotaxis in vitro and migration in vivo through interaction with CD18 and release of CCL4

Angiopoietins are a family of growth factors that are ligands for the tyrosine kinase receptor, Tie2. Angiopoietin 1 (Ang-1) is agonistic for Tie2, plays a key role in blood vessel maturation and stability and has been shown to possess anti-inflammatory properties. However, Tie2 expression has been demonstrated on human neutrophils and the observation that neutrophils migrate in response to Ang-1 in vitro has confounded research into its exact role in inflammation as well as its potential use as a therapeutic agent. We used a mouse model of peritoneal neutrophilic inflammation to determine if Ang-1 could stimulate neutrophil migration in vivo. Tie2 expression was demonstrated on mouse neutrophils. In addition, recombinant human Ang-1 induced significant chemotaxis of isolated mouse neutrophils in a Tie2- and CD18-dependent manner. Subsequently, co-immunoprecipitation of Ang-1 and CD18 demonstrated their interaction. Intraperitoneal injection of an engineered angiopoietin-1, MAT.Ang-1, induced significant neutrophil migration into the peritoneum and a significant increase in the levels of CCL4 in peritoneal lavage fluid. Depletion of resident peritoneal macrophages prior to, or concomitant injections of an anti-CCL4 antibody with MAT.Ang-1 resulted in a significant reduction in neutrophil recruitment. These data indicate a pro-inflammatory role for Ang-1 with respect to neutrophil recruitment.British Heart Foundation Studentship FS/06/081/2172

The pathophysiology of restricted repetitive behavior

Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism