Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder

AbstractAutism spectrum disorder (ASD) affects a significant number of individuals in the United States, with the prevalence continuing to grow. A significant proportion of individuals with ASD have comorbid medical conditions such as epilepsy. In fact, treatment-resistant epilepsy appears to have a higher prevalence in children with ASD than in children without ASD, suggesting that current antiepileptic treatments may be suboptimal in controlling seizures in many individuals with ASD. Many individuals with ASD also appear to have underlying metabolic conditions. Metabolic conditions such as mitochondrial disease and dysfunction and abnormalities in cerebral folate metabolism may affect a substantial number of children with ASD, while other metabolic conditions that have been associated with ASD such as disorders of creatine, cholesterol, pyridoxine, biotin, carnitine, γ-aminobutyric acid, purine, pyrimidine, and amino acid metabolism and urea cycle disorders have also been associated with ASD without the prevalence clearly known. Interestingly, all of these metabolic conditions have been associated with epilepsy in children with ASD. The identification and treatment of these disorders could improve the underlying metabolic derangements and potentially improve behavior and seizure frequency and/or severity in these individuals. This paper provides an overview of these metabolic disorders in the context of ASD and discusses their characteristics, diagnostic testing, and treatment with concentration on mitochondrial disorders. To this end, this paper aims to help optimize the diagnosis and treatment of children with ASD and epilepsy.This article is part of a Special Issue entitled “Autism and Epilepsy”

Alien Registration- Frye, Richard E. (Bowdoin, Sagadahoc County)

https://digitalmaine.com/alien_docs/8579/thumbnail.jp

Expendable oceanographic mooring (XMOOR)

An expendable, self-deploying mooring (XMOOR) for shallow water applications has been developed to address Navy requirements for environmental monitoring. The project has been conducted jointly between the Woods Hole Oceanographic Institution and the Naval Research Laboratory at Stennis, MS. WHOI has taken the lead on the mechanical design of the system while NR has developed the electronics. Eight prototype XMOOR systems have been built. They are designed for water depths between 10 and 100m, for deployments of up to 3-months duration, and for automatic deployment. Their sensor suite includes barometrc pressure, air temperatue, water temperature at up to 25 levels, and conductivity and pressure at up to 3 levels. Data telemetry is accomplished via the Argos DCS and by line-of-sight VH confguration of the data collection program. This report describes the XMOOR mechanical system. The data collection and telemetry systems are described separately in (1) and (2).Funding was provided by the Office of Naval Research through Contract Nos. NOOO-14-92-C-6028 and NOOO-14-95-1-0774

Mitochondrial Dysfunction Is Inducible in Lymphoblastoid Cell Lines From Children With Autism and May Involve the TORC1 Pathway

We previously developed a lymphoblastoid cell line (LCL) model of mitochondrial dysfunction in autism spectrum disorder (ASD); some individuals with ASD showed mitochondrial dysfunction (AD-A) while other individuals (AD-N) demonstrated mitochondrial respiration similar to controls (CNT). To test the hypothesis that mitochondrial dysfunction could be a consequence of environmental exposures through chronic elevations in reactive oxygen species (ROS), we exposed LCLs to prolonged ROS. We also examined expression of metabolic regulatory genes and the modulating effect of the mechanistic target of rapamycin (mTOR) pathway. Prolonged ROS exposure induced or worsened mitochondrial dysfunction in all LCL groups. Expression of genes associated with ROS protection was elevated in both AD-N and AD-A LCLs, but mitochondrial fission/fusion and mitoplasticity gene expression was only increased in AD-N LCLs. Partial least squares discriminant analysis showed that mTOR, UCP2 (uncoupling protein 2), SIRT1 (sirtuin 1), and MFN2 (mitofusin-2) gene expression differentiated LCL groups. Low-dose rapamycin (0.1 nM) normalized respiration with the magnitude of this normalization greater for AD-A LCLs, suggesting that the mammalian target of rapamycin complex 1 (mTORC1) pathway may have a different dynamic range for regulating mitochondrial activity in individuals with ASD with and without mitochondrial dysfunction, potentially related to S6K1 (S6 kinase beta-1) regulation. Understanding pathways that underlie mitochondrial dysfunction in ASD may lead to novel treatments.Arkansas Biosciences Institute (Little Rock, AR); Jonty Foundation (St. Paul, MN); Autism Research Institute (San Diego, CA); Gupta Family Foundation (Atherton, CA); Jane Botsford Johnson Foundation (New York, NY); Jager Family Foundation (Chicago, IL); Phoenix Children's Hospital Foundation (Phoenix, AZ)Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Mitochondrial Dysfunction Is Inducible in Lymphoblastoid Cell Lines From Children With Autism and May Involve the TORC1 Pathway

We previously developed a lymphoblastoid cell line (LCL) model of mitochondrial dysfunction in autism spectrum disorder (ASD); some individuals with ASD showed mitochondrial dysfunction (AD-A) while other individuals (AD-N) demonstrated mitochondrial respiration similar to controls (CNT). To test the hypothesis that mitochondrial dysfunction could be a consequence of environmental exposures through chronic elevations in reactive oxygen species (ROS), we exposed LCLs to prolonged ROS. We also examined expression of metabolic regulatory genes and the modulating effect of the mechanistic target of rapamycin (mTOR) pathway. Prolonged ROS exposure induced or worsened mitochondrial dysfunction in all LCL groups. Expression of genes associated with ROS protection was elevated in both AD-N and AD-A LCLs, but mitochondrial fission/fusion and mitoplasticity gene expression was only increased in AD-N LCLs. Partial least squares discriminant analysis showed that mTOR, UCP2 (uncoupling protein 2), SIRT1 (sirtuin 1), and MFN2 (mitofusin-2) gene expression differentiated LCL groups. Low-dose rapamycin (0.1 nM) normalized respiration with the magnitude of this normalization greater for AD-A LCLs, suggesting that the mammalian target of rapamycin complex 1 (mTORC1) pathway may have a different dynamic range for regulating mitochondrial activity in individuals with ASD with and without mitochondrial dysfunction, potentially related to S6K1 (S6 kinase beta-1) regulation. Understanding pathways that underlie mitochondrial dysfunction in ASD may lead to novel treatments

Development, Progress, and Accomplishments of Institutional Assessment at Western Washington University 1990 to 1996

Report 1996-02: Development, Progress, and Accomplishments of Institutional Assessment at Western Washington University-1990 to 1996 The fall of 1996 marked six years of assessment efforts at Western. In December, 1996, the Office of Institutional Assessment and Testing produced a six-year retrospective of its work. The original purpose of the Washington State\u27s assessment movement was to improve the quality of programs and provide performance accountability. These basic tenets have changed little in six years. Moreover, assessment did not just begin at Western in 1990. Before the statewide mandate for assessment, Western was already carrying out assessment activities: for instance, end-of-program assessment through capstone experiences, and surveys of in-coming freshmen. After the formalization of assessment, these activities provided a valuable basis from which to begin a much more encompassing and thorough approach to assessment. For instance, surveys on incoming freshmen had begun in 1971, which provided a rich statistical base for comparative longitudinal analyses. In its fledgling stages, Western Washington University\u27s Office of Institutional Assessment and Testing (OIAT) simply gathered information. A Student Tracking System was established. Numerous surveys and studies were conducted, and continue to be conducted. Indeed, OIAT researchers have created a vast and remarkable collection of survey and study findings, adding to it yearly. Surveys have been administered to students, faculty, staff, and administrators; to alumni, employers, and would-be employers of Western students; to non-matriculated former students, students admitted to Western who chose not to enroll, students who are the first in their family to attend college, and students participating in special programs. The OIAT has conducted analyses of English 101 writing samples and Fairhaven College student portfolios, compared various cohorts of native and transfer students

Greater Pre-Stimulus Effective Connectivity from the Left Inferior Frontal Area to other Areas is Associated with Better Phonological Decoding in Dyslexic Readers

Functional neuroimaging studies suggest that neural networks that subserve reading are organized differently in dyslexic readers (DRs) and typical readers (TRs), yet the hierarchical structure of these networks has not been well studied. We used Granger causality to examine the effective connectivity of the preparatory network that occurs prior to viewing a non-word stimulus that requires phonological decoding in 7 DRs and 10 TRs who were young adults. The neuromagnetic activity that occurred 500 ms prior to each rhyme trial was analyzed from sensors overlying the left and right inferior frontal areas (IFA), temporoparietal areas, and ventral occipital–temporal areas within the low, medium, and high beta and gamma sub-bands. A mixed-model analysis determined whether connectivity to or from the left and right IFAs differed across connectivity direction (into vs. out of the IFAs), brain areas, reading group, and/or performance. Results indicated that greater connectivity in the low beta sub-band from the left IFA to other cortical areas was significantly related to better non-word rhyme discrimination in DRs but not TRs. This suggests that the left IFA is an important cortical area involved in compensating for poor phonological function in DRs. We suggest that the left IFA activates a wider-than usual network prior to each trial in the service of supporting otherwise effortful phonological decoding in DRs. The fact that the left IFA provides top-down activation to both posterior left hemispheres areas used by TRs for phonological decoding and homologous right hemisphere areas is discussed. In contrast, within the high gamma sub-band, better performance was associated with decreased connectivity between the left IFA and other brain areas, in both reading groups. Overly strong gamma connectivity during the pre-stimulus period may interfere with subsequent transient activation and deactivation of sub-networks once the non-word appears

A Profile of the 1996 Western Washington University Graduating Class

Information on Western graduates of a given year: grades, retention, GEI, athletes, time-to-degree issues, demographics, college, degree, transfer facts, and predictors of academic success (regression analysis)

An Analysis of Student Evaluations of Instruction for the Fall Quarter 2004

An analysis of student evaluations of teaching. Trends, issues, etc

Individual Differences in Amygdala and Ventromedial Prefrontal Cortex Activity are Associated with Evaluation Speed and Psychological Well-being

Using functional magnetic resonance imaging, we examined whether individual differences in amygdala activation in response to negative relative to neutral information are related to differences in the speed with which such information is evaluated, the extent to which such differences are associated with medial prefrontal cortex function, and their relationship with measures of trait anxiety and psychological well-being (PWB). Results indicated that faster judgments of negative relative to neutral information were associated with increased left and right amygdala activation. In the prefrontal cortex, faster judgment time was associated with relative decreased activation in a cluster in the ventral anterior cingulate cortex (ACC, BA 24). Furthermore, people who were slower to evaluate negative versus neutral information reported higher PWB. Importantly, higher PWB was strongly associated with increased activation in the ventral ACC for negative relative to neutral information. Individual differences in trait anxiety did not predict variation in judgment time or in amygdala or ventral ACC activity. These findings suggest that people high in PWB effectively recruit the ventral ACC when confronted with potentially aversive stimuli, manifest reduced activity in subcortical regions such as the amygdala, and appraise such information as less salient as reflected in slower evaluative speed