The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System

Zoom Fatigue: Case Presentation and Brief Review

In this review, we discuss the phenomenon of what has been called Zoom Fatigue—a sense of fatigue as well as physical and emotional stress that can be associated with teleconferencing (especially long teleconferences with minimal breaks). The Zoom Fatigue Scale is discussed as well as various theories to explain the phenomenon. Some preventive strategies are discussed

Action and Function of ASB Proteins in Compartment Size Regulation

One of the most important and defining processes during development is the pattern formation of the various compartments in embryos. In an effort to discover the participants involved in regulating compartment size, we identified, in Danio rerio (zebrafish) embryos, the ankyrin repeat and SOCS box-containing protein 11 (d-asb11) gene. We first showed that d-Asb11 is a key mediator of Delta-Notch Signaling, acting at the level of DeltaA ubiquitylation, important in fine-tuning the lateral inhibition gradients between DeltaA and Notch. We, then, isolated a zebrafish having a germline deletion of the d-Asb11 cullin box subdomain and showed that this deletion resulted in loss of d-Asb11 activity. As a consequence, the animals were defective for Notch signaling and proper cell fate specification within the neurogenic regions of zebrafish embryos. We also provided evidence that d-Asb11 is important in maintaining myogenic proliferation in the stem cell compartment of zebrafish embryos and muscle regenerative responses in adult animals. This finding is supported by the highly specific d-Asb11 expression found in proliferating satellite cells in zebrafish muscle. In addition, we have applied immunoaffinity chromatograpy followed by tandem mass spectrometry to identify human ASB11 interacting proteins. The data confirmed the role of ASB11 as a subs

Comparison of maternal beliefs about causes of autism spectrum disorder and association with utilization of services and treatments

Background: This study aimed to describe parental perceptions of the causes of autism spectrum disorder (ASD) in an ethnically diverse sample and explore whether these perceptions relate to treatment choices. Methods: The sample consisted of White (n=224), Hispanic (n=85) and Asian (n=21) mothers of a child with ASD. A mixed methods approach was used in this secondary analysis focusing on parental perceptions about the causes of ASD and the relationship of these to utilization of services and treatment. Results: Environmental and genetic factors were most often believed to be the cause or one of the causes of ASD by mothers across all ethnic groups studied. Asian mothers were more likely to cite multiple causes. Environmental causes were associated with receiving 20 or more hours of autism related services per week; while belief in environmental exposures and vaccines and medications as causes were associated with complementary-alternative medicine (CAM) use. Conclusion: Our findings suggest that ethnic differences in autism causal beliefs and treatment choices may exist. Future research should be conducted to specifically confirm the findings, to understand parental motivation behind their service and treatment choices; and to gain more insight into the types, usage and sources of CAM treatments. Clinicians can use parental autism causal beliefs in discussions about treatment recommendations

Global increases in both common and rare copy number load associated with autism.

Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism

Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD) controls and children with developmental delays (DD) other than ASD. We found that levels of anti-cardiolipin, β2-glycoprotein 1, and anti-phosphoserine antibodies were elevated in children with ASD compared with age-matched TD and DD controls. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD

GeneDB--an annotation database for pathogens.

GeneDB (http://www.genedb.org) is a genome database for prokaryotic and eukaryotic pathogens and closely related organisms. The resource provides a portal to genome sequence and annotation data, which is primarily generated by the Pathogen Genomics group at the Wellcome Trust Sanger Institute. It combines data from completed and ongoing genome projects with curated annotation, which is readily accessible from a web based resource. The development of the database in recent years has focused on providing database-driven annotation tools and pipelines, as well as catering for increasingly frequent assembly updates. The website has been significantly redesigned to take advantage of current web technologies, and improve usability. The current release stores 41 data sets, of which 17 are manually curated and maintained by biologists, who review and incorporate data from the scientific literature, as well as other sources. GeneDB is primarily a production and annotation database for the genomes of predominantly pathogenic organisms

SIGffRid: A tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics

<p>Abstract</p> <p>Background</p> <p>Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (<it>σ</it>) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations.</p> <p>Results</p> <p>We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of <it>Streptomyces coelicolor </it>and <it>Streptomyces avermitilis</it>. Cross-check with the well-defined SFBSs of the SigR regulon in <it>S. coelicolor </it>is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these <it>σ </it>factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. <it>Escherichia coli</it>/<it>Salmonella typhimurium </it>and <it>Bacillus subtilis</it>/<it>Bacillus licheniformis </it>pairs). Motifs of house-keeping <it>σ </it>factors were found as well as other SFBSs such as that of SigW in <it>Bacillus </it>strains.</p> <p>Conclusion</p> <p>We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs. The method versatility autorizes the recognition of other kinds of two-box regulatory sites.</p