Grantee Research Project Results
2012 Progress Report: UC Davis Center for Children’s Environmental Health
EPA Grant Number: R833292Center: UC Davis Center for Children's Environmental Health and Disease Prevention
Center Director: Van de Water, Judith
Title: UC Davis Center for Children’s Environmental Health
Investigators: Pessah, Isaac N.
Current Investigators: Pessah, Isaac N. , Berman, Robert F. , Bennett, Deborah H. , Golub, Mari S. , Walker, Cheryl , Hertz-Picciotto, Irva , Van de Water, Judith , Ashwood, Paul , Hansen, Robin , Ozonoff, Sally
Institution: University of California - Davis
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2006 through October 31, 2011 (Extended to October 31, 2013)
Project Period Covered by this Report: November 1, 2011 through October 31,2012
Project Amount: $3,782,733
RFA: Centers for Children’s Environmental Health and Disease Prevention Research (2005) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
R83329201C001: Environmental Epidemiology
To build upon our discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) Study.
R83329201C002: Immunological Susceptibility of Autism
Our current aims include the continued examination of environmental toxicants such as PBDE47 on immune function in children with autism. In addition, we are currently working on the identification of the autoantigens in both the maternal population and their offspring. We will bring back our subjects for a longitudinal analysis of their immune function parameters studied previously. We have been performing B cell function analysis using PBMC from CHARGE-BACK subjects. We are currently waiting to obtain more typically developing (TD) subjects for this aspect of the study prior to data analysis.
R83329201C003: Neurodevelopmental Toxicology
The specific aims of Project 3 remain essentially unchanged for year 11 of the grant. The overall goal of Project 3 has been to determine if exposure to environmental toxicants early in development contributes to the etiology of autism and related neurodevelopmental disorders. Two related goals are to determine whether syndromic forms of autism (e.g., MECP2 mutations or FMR1 mutations) susceptibility to environmental contaminants (PCB and PBDEs) increases the severity for neurodevelopmental outcomes, and if maternal autoantibodies found in women at risk for birthing an autistic child promote social impairments in a perinatal mouse model we have developed. Specific Aim 1 examines perinatal exposure to BDE47 and PCB 95 in C57BL/6J mice for effects on spatial memory and learning, sensory and motor development, sensory gating and fear/anxiety. Specific Aim 2 examines whether neonatal exposure to environmental contaminants alters immune system function, determined by exposing mice to toxins and measuring immunoglobulins, cytokines and chemokines. Specific Aim 3 examines whether neonatal toxin exposure alters brain excitability. Specific Aim 4 is designed to determine whether injection of immunoglobulins isolated from the serum of mothers of autistic children into pregnant mice alters brain development and behavior.
Community Outreach and Translation Core
The Community Outreach and Translation Core (COTC) has two distinct and interrelated objectives. The first objective is to coordinate and implement an efficient and highly effective clinical interface between CCEH investigators and study participants. The second objective of the COTC is to translate scientific findings from CCEH research into simplified text and presentations in both English and Spanish that are more easily understood by study participants, our community partners, clinicians, state officials and the general public.
Analytical Core
Objective 1. Establish the metabolic pathways responsible for variations in lipid composition between autistic children and their siblings and between normal and immunologically challenged animal models of autism.
Objective 2. Use global metabolomic procedures to search for biomarkers of autism.
Objective 3. Provide analytical data on pesticide and other xenobiotic levels in cell and in vivo model systems and in serum samples from the CHARGE, CHARGE-BACK, MARBLES and other successor studies.
Objective 4. Develop new analytical methods for xenobiotics of interest to scientists in the program project.
Molecular Genomics Core
Objective 1: Establish if genomic profiles in the blood of children with autism are different from GP and MR/DD children. If the genomic profiles in autism are due to environmental toxicants, these will change over time. If the genomic profiles in autism are due to genetic/hereditary factors, these will remain constant over time. Different toxicants or different genetic/hereditary factors will produce different genomic profiles in blood and potentially differentiate groups of children with autism due to different causes. This core will contribute to Project 1 in the following ways.
1.1. Perform genomic (expression microarray) studies on blood from children with autism in the 4-9 year old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age range.
1.2. Compare gene expression as a function of blood metal levels in age groups in A, A-R, ASD, MR/DD and GP groups.
1.3. Examine genomic profiles in pregnant mothers who have given birth to a previous child with autism, and determine if there is a specific genomic profile that correlates with whether the mother is carrying a child destined to develop autism.
Objective 2. Determine if immune function in subgroups of children with autism as shown by abnormal cytokines, chemokines and autoantibodies will correlate with differences of gene expression in specific cell types in the blood of children with autism compared to GP and MR/DD children. Abnormalities in NK cells are postulated to account for at least some of the abnormal immune functions. This core will contribute to Project 2 in the following ways.
2.1. Describe the gene expression profiles in the blood using specific white blood cell subsets for children with autism without regression, autism with regression, and ASD children compared to GP and MR/DD children.
2.2. Examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics.
Statistical Analysis Core
The main objective of the Statistics Core (SC) is to provide CCEH researchers with statistical support and collaboration for autism research ranging from animal models to childrens clinical and population-based studies. SC faculty continue to collaborate with investigators in the development of new projects, in providing data analysis support, and by advising on statistical analysis and experimental design. Finally, we have continued the research program in developing methodology for targeted methodologies motivated by CCEH studies. The Specific Aims of this Core are:
- To assist CCEH researchers with study design and planning, including study design and framing of aims and hypotheses; sample size and power calculation; and analytical planning.
- To assist CCEH researchers with data analysis and presentation of results from each Project and Core.
- To advise and assist CCEH researchers with the linkage of databases across Projects and Cores and on analysis of the resulting complex data and research questions.
- To foster development of necessary new biostatistics methods specific to the field of autism research by supporting applications for funded research, linking CCEH investigators who have challenging problems with statistical researchers specializing in related areas, and encouraging graduate students in statistics/biostatistics to consider dissertations in this area.
Progress Summary:
R83329201C001: Environmental Epidemiology
Specific Aim 1.
Hypothesis: Children with autism can be distinguished from those without autism by markers of immune dysregulation (at birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures.
Substantial work continued on this aim. Using data from the CHARGE Study, we added further evidence after publishing on a marked increase in pro-inflammatory IL-1beta, IL-6, and TNF-alpha responses following TLR 2, IL-1beta response following TLR 4 stimulation in monocyte cultures from children with ASD (Ashwood et al., Brain Behav Immun 2010) and on an association between pro-inflammatory cytokines and worse behaviors in core domains for ASD, while GM-CSF and TH-2 cytokines were associated with improved cognitive function (Ashwood et al., Brain Behav Immun 2011). As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD. Additionally, several chemokines (MCP-1, RANTES, eotaxin) were elevated in plasma of affected children and associated with deviant behaviors and poorer developmental scores (Ashwood et al., J Neuroimmunology 2011). Moreover, using western blot, we found that children with autism or ASD produce distinct patterns of plasma auto-antibodies to cerebellum proteins and that the presence of these antibodies correlates with worse behaviors and lower scores in cognitive and adaptive domains (Goines et al 2011, Autoantibodies to cerebellum in children with autism associated with behavior. Brain Behav Immun 2011;25(3):514-23. PMID: 21134442).
In epidemiologic work, we examined immunologically relevant events in the prenatal period for autism. With statewide records on over 6 million births, we showed that conception for children who developed autism was more likely to be in the winter months, December through March (Zerbo et al., Epidemiology 2011), a finding consistent with an early infectious exposure. Second, in CHARGE Study participants, mothers of children with confirmed autism were more likely, though not significantly so, to report having had flu in the second trimester, and also more likely to report an untreated fever, i.e., fever for which no medication was taken. Indeed, in children whose mothers did report a fever that they did not medicate with antipyretics, the risk of autism was no different from offspring of mothers without fever. For children whose mothers had a fever but did not medicate, the odds ratio was over two-fold (Zerbo et al., 2012). These findings strongly support that the maternal inflammatory response to fever, which generates a so-called cytokine storm, may be acting to adversely affect brain development.
Third, we examined several maternal chronic conditions that are associated with inflammation: diabetes or gestational diabetes, hypertension, and obesity. Children with autism were more likely to have a mother who had one or more of these conditions, with an OR of 1.61, 95% CI=(1.10, 2.37). These conditions were also associated with greater risk for developmental delay and with lower scores in expressive or receptive language in both the ASD and non-ASD group separately (Krakowiak et al., 2012). In further work, the maternal metabolic conditions are being examined in association with cytokines measured in the newborn blood spots.
This project also collaborated with Project 2 in collection and analysis of specimens for the CHARGE-Back study, which examined continuity of markers of dysregulated immune function.
Specific Aim 2.
Hypothesis: Children with autism can be distinguished from children without autism by their xenobiotic exposures and biomarkers, which in turn are related to immune dysregulation.
We continued our investigations of mercury, air pollution and nutritional factors. We completed analyses of baby hair specimens and validated their correlation with fish consumption. Some difficulties with the solid standards for hair mercury became apparent with the second batch of hair specimens that were analyzed, and the analytic chemists (Dr. Green and colleagues) had to develop our own standards for this work. That development was completed in summer of 2012, and the re-analysis of batch two along with a third batch has now been accomplished. To date, using the high quality batch one set, we saw no association of infant hair mercury levels with diagnostic group (autism, developmental delay, typical development) (McKean et al., in revision). A second study used newborn blood spots and also found no association with autism risk, and no evidence of an interaction with childs genotype for GSTM1. We are expanding our sample size, based on the additional shipment of more than 650 more newborn bloodspots. A third manuscript has investigated the use of the bloodspots and the questionnaires to develop a toxicokinetic model for fish levels of mercury in pregnant women (McKean et al., in preparation).
Air pollution and proximity to traffic as a proxy for exposure to motor vehicle emissions were also examined using the CHARGE Study participant addresses during pregnancy and at the time of delivery. Mapping of addresses and geocoding to calculate distance to the nearest freeway revealed that case families were nearly twice as likely to reside within 300 m of a freeway as compared with control families (OR=1.86, 95% CI= 1.04, 3.45) (Volk et al., Env Health Persp 2011). Further work has been conducted using estimated exposures to fine particles using several exposure databases, and results indicate similar and larger associations with NO2 and fine particles (Volk et al., Traffic related air pollution, particulate matter, and autism. Arch Gen Psychiatr 2012 (just published in November).
With regard to household products, detailed analyses reveal a consistent link between use of insecticide sprays or foggers in the house, or use of household pyrethroid-containing insecticides during the gestational period and risk for autism. The risks exceeded three-fold for those who used pyrethroid-containing products regularly (e.g., 3 months in the first and second trimester, or 6 months in the full pregnancy). We found that associations were weaker when animal flea and tick products or pyrethrin-only insecticides were evaluated, but stronger when restricted to those who were born 2002 or later (after the banning of organophosphates for household products) or in those boys who carried the 4-repeat allele in the promoter region of the MAOA gene. These differentials in the associations suggest that recall bias is unlikely to explain the findings (Hertz-Picciotto et al., in submission).
Finally, maternal report of prenatal vitamin supplementation was assessed in relation to risk for autism or ASD. Results showed that mothers of affected children were less likely to report having taken prenatal vitamins in the period from three months prior to conception through the first month of pregnancy (Schmidt et al., 2011). By the end of the first trimester, the vast majority of mothers of both cases and controls were taking these vitamins. Thus, this finding points to a very early window of susceptibility. Also, if either the mother or the child inherited a genotype for one of the critical genes encoding enzymes in the one-carbon-metabolism cycle that involved less efficient transfer of methyl groups to DNA, the child was at much higher risk when the mother had not supplemented with vitamins in the critical window (Schmidt et al., 2011). In further work, dietary and supplemental sources of folic acid in the first month of pregnancy were quantified; intake was associated with reduced risk, such that mothers of typically developing controls were more likely to report consuming more than 600 micrograms per day (Schmidt et al., Maternal periconceptional folic acid intake and risk for autism spectrum disorders in the CHARGE case-control study. Am J Clin Nutrition 2012 Jul;96(1):80-9. PMID: 22648721). The burden of risk was primarily in mother-child pairs where one or both carried the inefficient metabolizing genotype of MTHFR677.
Specific Aim 3.
Hypothesis: Transcriptional genomic profiles of children with autism differ from those of children without autism.
Transcriptional analysis of CHARGE Study samples was reported in a previous year, and several manuscripts were published suggesting that the relationship of gene expression to mercury and lead differs by case status (Tian et al., 2011, Stamova et al., 2011). Similar analysis on MARBLES subjects will await further information on final diagnoses, in order to maximize our statistical efficiency by choosing an efficient ratio of cases:controls.
Specific Aim 4.
Hypothesis: The exposure and biomarker (immune, xenobiotic, genomic) differences will be most pronounced for specific phenotypic subsets among children in the CHARGE study.
Results for Specific Aims 1 and 2 demonstrate that: several genetic polymorphisms influence susceptibility to environmental factors (nutrition, pesticides); language impairment shows a particularly strong association with maternal metabolic conditions; and aberrant behaviors cluster more heavily among cases with markers of immune dysregulation.
Grants generated as a result of this project:
An add-on study to examine air pollution from traffic and predisposing SNPs was funded for our collaborator at the University of Southern California, Dr. Heather Volk, 1R21ES019002-01, "INVESTIGATING GENE-ENVIRONMENT INTERACTION IN AUTISM: AIR" FUNDED BY NIEHS (ARRA) FOR THE PERIOD 9/28/09-7/31/10.
Autism Speaks has been funding a cooperative agreement with Co-PIs Dr. Schmidt and Dr. Walker to develop, refine, validate and test feasibility of standardized forms for collection of critical prenatal exposure data on nutrition, maternal conditions and environmental exposures. These instruments will be made available for other researchers seeking a relatively condensed set of questions to add on to studies not primarily aimed at examining these types of environmental factors.
Several ARRA supplements to the CHARGE Study (R01-ES015359-S1, S2, S3, and S4) were obtained. One of these provided funding to examine dust samples collected from CHARGE Study homes where the child was still living in the same home as when he/she was born in order to measure residues of pesticides, flame retardants, and phthalates. Preliminary analyses have been completed and a manuscript is in preparation. The work of Dr. Schmidt on maternal nutrition and the work of Dr. Zerbo on maternal fever were both partially funded by one of these supplements. Dr. Virginia Chaidez was also funded to analyze ethnic differences in autism comparing Hispanic and non-Hispanic families (Chaidez et al., Autism spectrum disorders in Hispanics and non-Hispanics. Autism: The International Journal of Research and Practice 2012;16(4): 381-397. PMID: 22399446. http://aut.sagepub.com/content/early/2012/02/23/1362361311434787 Exit); her work on GI symptoms is being revised for resubmission. Final reports of these supplements have been submitted separately.
The MARBLES Study has received an NIH grant (R01-ES020392, Multiple PIs: Hertz-Picciotto, Pessah, Ozonoff) to continue recruitment for this prospective examination of environmental factors for another five years. The purpose of this study is to pursue hypotheses regarding early life exposures in relation to pyrethroid pesticides and PBDEs, and to identify early biologic markers of risk.
A pilot study collaboration with NIOSH provided preliminary data leading to the awarding of a new contract to examine parental occupational exposures in relation to autism (Parental Occupational Exposures and Gene Data Study, NIOSH #200201250927; PI: Hertz-Picciotto).
Significance:
By now the UC Davis Center on Childrens Environmental Health has generated convincing evidence regarding immunologic dysregulation leading to increased pro-inflammatory activity in children with autism, and a statewide analysis indicates a seasonal contribution to increased risk based on conception in the winter months. Additional analyses of the CHARGE Study indicate that second trimester fever, uncontrolled by medication, may also confer higher risk of autism in the offspring. Similarly, chronic inflammatory conditions of the pregnant mother may predispose the child to a higher risk for ASD and poorer cognitive development. These findings together support a potential inflammatory involvement potentially originating in the prenatal period, and either leading to or exacerbating neuropathologic events.
Our findings with regard to xenobiotic chemical and particle exposures may provide opportunities for interventions. First, traffic and estimated air pollution concentrations appear to be associated with elevated risk for ASD, suggesting that our current regulations may not be sufficient to protect the developing fetus. Household pyrethroid insecticides, synthesized for high toxicity mediated by voltage-sensitive sodium channels and also known for interference with GABA-receptors, were more commonly used by families whose child developed autism than by those whose child showed typical development. These compounds are currently advertised as being safe and natural. The particularly high risk associated with frequent use and in those with a high risk genotype are of concern. In contrast, maternal consumption of prenatal supplements appears to have a protective influence on child development, with reduced risk of autism when these were taken in the periconception. GeneXenvironment interactions provide further evidence that the findings are not due to differential reporting by parents according to case-control status of the child. The potential for intervention on these factors as an avenue to decrease incidence of ASD should be pursued.
R83329201C002: Immunological Susceptibility of Autism
1) Effects of in vitroBDE 49 exposure: To examine the effect of PBDE 49 on immune cell function in vitro, we have expanded our studies of immunotoxicant sensitivity to BDE49 based on some data from the Pessah and Lein labs that suggest increased toxicity on cultured neurons (Kim et al., 2011). We noted several key findings: 1) Regardless of diagnosis, ex vivo exposure of PBMC from children 2-5 years of age to BDE-49 profoundly affects immune cell function in terms of increased cytokine/chemokine production. Many pro-inflammatory cytokines were increased including IL-1b, TNF-a and IL-6, all known to have large effects on neuronal function, migration, proliferation, differentiation and a role in synapse formation (90). This was especially evident in males (n=75) where a predominantly inflammatory profile was indicated (Figure 1);
Figure 1. Effect of 50 nM BDE-49 exposure on cytokine/chemokine production by PBMC from males (n=75), regardless of diagnosis.
2) Further, when we examined the effects of BDE-49 exposure on children with ASD compared to TD controls, we noted a differential effect of BDE-49 with an increased production of several cytokines, including IL-6, TNFa and IL-1a, in children with ASD compared to a decrease in the TD controls (Figure 2); 3) When we activated the cells ex vivo following a 4-hour pre-incubation with BDE-49, then followed by stimulation with LPS we see a similar differential response for IL-13 (p=0.07), IL-17 (p=0.09), MCP-1 (p=0.08) and MIP-1b (p=0.04) where mean fold change was derived from logn transformed pg/ml cytokine production (Treatment-Baseline/Baseline) (t-test,*p=<0.05). No differences in cell viability or apoptosis/necrosis were detected after BDE-49 exposure in any the different groups or after the stimulation with PHA or LPS, suggesting that the BDE-49 was selectively altering cytokine production rather than an apoptosis effect.
Figure 2. Cellular Immune Response of Immune Cells from subjects with AU compared to age-matched typically developing controls, TD to 50nM BDE-49. In 50 nM BDE-49 exposed cells followed by PHA challenge there was a differential increase in IL-1 (*p=0.02), TNF- (p=0.07), IL-13 (*p=0.05) and IL-6 (*p=0.02). Mean fold change was derived from logn transformed pg/ml cytokine production (Treatment-Baseline/Baseline). (t-test,*p=<0.05)(t-test,*p=<0.05) )(n=98, F=23, M=75, AU=29, DD=16, TD=53).
Thus, certain environmental toxicants may alter the cytokine/chemokine response, resulting in inappropriate cytokine production following activation. This might reflect the ability of these toxicants to alter common signaling pathways that could affect both immune and neuronal function. The presentation of this work won second place for pre-doctoral candidates at the Neurotoxicology meeting in November 2011.
2) Analysis of B cell function to determine origin of IgG and IgM deficits in ASD: We performed extensive studies on their isolated B cells (those cells responsible for antibody production). Our results demonstrated no differences in the B cell parameters measured, indicating that decreased IgG in autism is not a result of B cell dysfunction and other immune cells might be involved (Heuer et al., JNI 2012) (Figure 3).
Figure 3. Median quantities of immune cell subsets in peripheral blood as determined by flow cytometry.Whole blood from both autism and typically developing controls were stained using fluorochrome conjugated antibodies directed against cell surface phenotypic markers. Absolute quantification of peripheral blood immune cell populations was then carried out by flow cytometry using counting beads. We found no significant differences in the absolute quantity of CD19+ B cells (A), CD3+ T cells (B), CD14+ Monocytes (C), CD19+CD27-IgD+ Naïve B cells (D), CD19+CD27+IgM+ Memory B cells (E), or CD19+CD27+IgG+ Memory B cells (F).
We will next expand our focus of cellular dysfunction to include the cells ancillary to antibody production, the T helper cells and the antigen presenting cells. Functional analysis for this first stage will be in terms of cytokine production that is involved in antibody production and following cell activation
3) Maternal autoantibodies to fetal brain proteins: The presence of these antibodies in the plasma of some mothers of children with autism might suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing autism in some children. We have now identified six different proteins recognized by maternal antibodies, reactivity to which is found in 23% of mothers of children with autism. This paper has been submitted for review.
In conclusion, we continue to define the immune profile of children with ASD as well as the maternal autoantibody profile in the MARBLES study. We have also determined a differential sensitivity to the PBDE family of persistent organic pollutants, and will continue to expand our mechanistic studies in collaboration with the Pessah lab. The maternal antibody antigen identification paper will be published in early 2013.
Project-Generated Resources: Autism Speaks generated funding, NIEHS funding for MARBLES.
R83329201C003: Neurodevelopmental Toxicology
Molecular, Cellular and Behavioral Toxicology
PBDEs and PCBs: Polybrominated diphenyl ethers (PBDEs) are flame retardants used worldwide in a variety of commercial goods, and are now widely found in both environmental and biological samples. BDE-47 is one of the most pervasive of these PBDE congeners and therefore is of particular concern. During this project period we completed and published two studies using wild type and MECP2 knock out mice in the C57BL/6J background and one paper on PCB/PBDE levels in postmortem human brain samples. First we documented accumulation of BDE-47 in several organ systems following perinatal exposure of WT mice to low-levels of BDE-47, and provided evidence that such exposure is associated with early behavioral deficits in exposed neonates (Koenig et al., 2012). Mice were exposed perinatally to 0.03, 0.1 or 1mg/kg/day of BDE-47, a dose range chosen to encompass human exposure levels. Tissue levels of BDE-47 were measured in the blood, brain, fat and milk of dams and in whole fetal homogenate and blood and brain of pups on gestational day (GD) 15, and postnatal days (PNDs) 1, 10 and 21. From GD 15 to PND 1, levels of BDE-47 increased within dam tissues and then decreased from PNDs 1 to 21. Over the period of lactation, levels in dam milk were comparatively high when compared to both brain and blood for all dose groups. Measurable levels of BDE-47 were found in the fetus on GD 15 confirming gestational exposure. From PNDs 1 to 21, levels of BDE-47 in pup tissue increased over the period of lactation due to the transfer of BDE-47 through milk. Behavioral tests of fine motor function and learning and memory were carried out between postnatal weeks 5-17 in order to evaluate the neurobehavioral toxicity of BDE-47. Behavioral deficits were only seen in the Barnes spatial maze where mice in the three exposure groups had longer latencies and traveled longer distances to find the escape hole when compared to vehicle control mice. These results support the conclusions that perinatal exposure to BDE-47 can have neurodevelopmental consequences, and that lactational exposure represents a significant exposure risk during development.
In the second mouse study, we investigated whether epigenetic mechanisms, such as DNA methylation, are responsive to environmental influences and have long-lasting consequences. Since autism spectrum disorders (ASDs) have complex neurodevelopmental origins whereby both genetic and environmental factors are implicated, we tested whether mice with a Rett syndrome mutation in methyl-CpG binding protein 2 (Mecp2(308)) have heightened sensitivity to long-lasting effects of PBDE exposure (Woods et al., 2012). Mecp2(308/+) dams were perinatally exposed daily to 2,2',4,4'-tetrabromodiphenyl ether 47 (BDE-47) and bred to wild-type C57BL/6J males, and the offspring of each sex and genotype were examined for developmental, behavioral and epigenetic outcomes. Perinatal BDE-47 exposure negatively impacted fertility of Mecp2(308/+) dams and preweaning weights of females. Global hypomethylation of adult brain DNA was observed specifically in female offspring perinatally exposed to BDE-47 and it coincided with reduced sociability in a genotype-independent manner. A reversing interaction of Mecp2 genotype on BDE-47 exposure was observed in a short-term memory test of social novelty that corresponded to increased Dnmt3a levels specifically in BDE-47-exposed Mecp2(308/+) offspring. In contrast, learning and long-term memory in the Morris water maze was impaired by BDE-47 exposure in female Mecp2(308/+) offspring. These results demonstrate that a genetic and environmental interaction relevant to social and cognitive behaviors shows sexual dimorphism, epigenetic dysregulation, compensatory molecular mechanisms and specific behavioral deficits.
The relationship between PBDE/PCB levels and DNA methylation patterns in the brains of individuals with and without neurodevelopmental disorders has not been previously investigated. In a study we recently published (Mitchell et al., 2012), a total of 107 human frozen postmortem brain samples were analyzed for eight PCBs and seven PBDEs by GC-micro electron capture detector and GC/MS using negative chemical ionization. Human brain samples were grouped as neurotypical controls (n = 43), neurodevelopmental disorders with known genetic basis (n = 32, including Down, Rett, Prader-Willi, Angelman, and 15q11-q13 duplication syndromes), and autism of unknown etiology (n = 32). Unexpectedly, PCB 95 was significantly higher in the genetic neurodevelopmental group, but not idiopathic autism, as compared to neurotypical controls. Interestingly, samples with detectable PCB 95 levels were almost exclusively those with maternal 15q11-q13 duplication (Dup15q) or deletion in Prader-Willi syndrome. When sorted by birth year, Dup15q samples represented five out of six of genetic neurodevelopmental samples born after the 1976 PCB ban exhibiting detectable PCB 95 levels. Dup15q was the strongest predictor of PCB 95 exposure over age, gender, or year of birth. Dup15q brain showed lower levels of repetitive DNA methylation measured by LINE-1 pyrosequencing, but methylation levels were confounded by year of birth. These results demonstrate a novel paradigm by which specific POPs may predispose to genetic copy number variation of 15q11-q13. The results from these studies indicate the potential significance of PCB 95 exposures to human developmental health.
In this regard, we also completed and published two detailed mechanistic studies of how PCB 95 alters activity-dependent dendritic growth by altering the functions of ryanodine receptors and its downstream Ca2+-dependent signaling pathways (Wayman et al., 2012a; 2012b). In the first paper, we demonstrate that environmentally relevant levels of NDL PCBs modulate neuronal connectivity via RyR-dependent effects on dendritic arborization. In addition, these findings identify RyR channel dysregulation as a novel mechanism contributing to dysmorphic dendritogenesis associated with heritable and environmentally triggered neurodevelopmental disorders.
In the second companion paper, we tested the hypothesis that the CaMKI-CREB-Wnt2 signaling pathway couples NDL PCB-enhanced RyR activity to dendritic arborization. RyRs regulate the spatiotemporal dynamics of intracellular Ca(2+) signals, but whether RyRs promote dendritic growth via the modulation of this signaling pathway is not known. Ca(2+) imaging of dissociated cultures of primary rat hippocampal neurons indicated that PCB-95 (2,2',3,5'6-pentachlorobiphenyl; a potent RyR potentiator) enhanced synchronized Ca(2+) oscillations in somata and dendrites that were blocked by ryanodine. As determined by Western blotting and quantitative polymerase chain reaction, PCB-95 also activated CREB and up-regulated Wnt2. Blocking CaMKK, CaMKIα/γ, MEK/ERK, CREB, or Wnt2 prevented PCB-95-induced dendritic growth. Antagonism of γ-aminobutyric acid (GABA) receptors with bicuculline (BIC) phenocopied the dendrite-promoting effects of PCB-95, and pharmacological antagonism or siRNA knockdown of RyR blocked BIC-induced dendritic growth in dissociated and slice cultures of hippocampal neurons. We therefore concluded that RyR activity contributes to dynamic remodeling of dendritic architecture in response to NDL PCBs via CaMKI-CREB-Wnt2 signaling in rats. Our findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling associated with autism.
Pesticides: We published a seminal paper identifying the molecular mechanisms by which the pesticide, triclosan, which is broadly used as an antibacterial, impairs EC coupling in skeletal and cardiac muscle and impairs contractility in vivo (Cherednichenko et al., 2012). The origin of this work follows our discovery of the biological activity of hydroxylated PBDEs we previously reported in our last progress statement (Kim et al., 2011). In addition we published an extensive review of the literature regarding pesticides and autism risk (Shelton et al., 2012).
Mouse model of maternal autoantibody transfer: We completed a detailed investigation of a murine passive transfer model system to ascertain the effects of gestational exposure to a single, intravenous dose of purified, brain-reactive IgG antibodies from individual mothers of children with autism (MAU) or mothers with typically developing children (MTD) (Braunschweig et al., 2012). Growth and behavioral outcomes in offspring were measured from postnatal days 8 to 65 in each group. Comparisons revealed alterations in early growth trajectories, significantly impaired motor and sensory development, and increased anxiety. This report demonstrates for the first time the effects of a single, low dose gestational exposure of IgG derived from individual MAU on their offspring's physical and social development.
FMR1 models of autism: We have published several papers this year that develop both a mouse and human model of ASD. In the mouse FMR1premutation model we have shown that defects in neuronal morphology and migration previously described by us (Chen et al., 2010; Cunningham et al., 2011) in a preCGG mouse model are associated with functional abnormalities (Cao et al., 2012). Mouse preCGG hippocampal neurons (170 CGG repeats) grown in vitro develop abnormal networks of clustered burst (CB) firing, as assessed by multielectrode array recordings and clustered patterns of spontaneous Ca(2+) oscillations, neither typical of wild-type (WT) neurons. PreCGG neurons have reduced expression of vesicular GABA and glutamate (Glu) transporters (VGAT and VGLUT1, respectively), and preCGG hippocampal astrocytes display a rightward shift on Glu uptake kinetics, compared with WT. These alterations in preCGG astrocytes and neurons are associated with 4- to 8-fold elevated Fmr1 mRNA and occur despite consistent expression of fragile X mental retardation protein levels at ∼50% of WT levels. Abnormal patterns of activity observed in preCGG neurons are pharmacologically mimicked in WT neurons by addition of Glu or the mGluR1/5 agonist, dihydroxyphenylglycine, to the medium, or by inhibition of astrocytic Glu uptake with dl-threo-β-benzyloxyaspartic acid, but not by the ionotropic Glu receptor agonists, α-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid or N-methyl-d-aspartic acid. The mGluR1 (7-(hydroxyimino)cyclopropa [b]chromen-1a-carboxylate ethyl ester) or mGluR5 (2-methyl-6-(phenylethynyl)pyridine hydrochloride) antagonists reversed CB firing. Importantly, the acute addition of the neurosteroid allopregnanolone mitigated functional impairments observed in preCGG neurons in a reversible manner. These results demonstrate abnormal mGluR1/5 signaling in preCGG neurons, which is ameliorated by mGluR1/5 antagonists or augmentation of GABA(A) receptor signaling, and identify allopregnanolone as a candidate therapeutic lead but also implicating mechanisms that could implicate gene x environment interactions. We also published evidence of early mitochondrial impairments in this mouse model (Kaplan et al., 2012).
We have also developed a human iPSC-derived neuronal cell model from human premutation patients (Liu et al., 2012). To investigate the underlying cellular neuropathology, we produced induced pluripotent stem cell-derived neurons from isogenic subclones of primary fibroblasts of a female premutation carrier, with each subclone bearing exclusively either the normal or the expanded (premutation) form of the FMR1 gene as the active allele. We show that neurons harboring the stably-active, expanded allele (EX-Xa) have reduced postsynaptic density protein 95 protein expression, reduced synaptic puncta density and reduced neurite length. Importantly, such neurons are also functionally abnormal, with calcium transients of higher amplitude and increased frequency than for neurons harboring the normal-active allele. Moreover, a sustained calcium elevation was found in the EX-Xa neurons after glutamate application. By excluding the individual genetic background variation, we have demonstrated neuronal phenotypes directly linked to the FMR1 premutation. Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g. autism) and neurodegenerative (e.g. Parkinsonism, dementias) disorders.
Genetics of Autism: Expansion of a CGG trinucleotide repeat (>200 repeats) in the 5'UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies for FXS, among individuals with ID from different ethnic populations, have indicated that the prevalence of the syndrome varies between 0.5 and 16%. Because of the high co-morbidity with autism, we have conducted a screening study of the cohort from CHARGE, a large-scale, population-based, case control study. We have identified six subjects carrying an expanded allele, which emphasize the importance of screening for FXS in a population with intellectual disabilities and ASD (Tassone et al., 2012).
Project-Generated Resources:
NIEHS and Autism Speaks supplements for the NCE. NIEHS funding for MARBLES continuation.
Significance:
1) Our study results support the conclusion that perinatal exposure to BDE-47 can have neurodevelopmental consequences, and that lactational exposure represents a significant exposure risk during development. 2) We have also shown that a genetic and environmental interaction relevant to social and cognitive behaviors shows sexual dimorphism, epigenetic dysregulation, compensatory molecular mechanisms and specific behavioral deficits.
3) Our results demonstrate a novel paradigm by which specific POPs may predispose to genetic copy number variation of 15q11-q13. The results from these studies indicate the potential significance of PCB 95 exposures to human developmental health. 4) Our findings identify RyR channel dysregulation as a novel mechanism contributing to dysmorphic dendritogenesis associated with heritable and environmentally triggered neurodevelopmental disorders. 5) Our studies identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling associated with autism. 6) We published a seminal paper identifying the molecular mechanisms by which the pesticide, triclosan, which is broadly used as an antibacterial, impairs EC coupling in skeletal and cardiac muscle and impairs contractility in vivo. 7) We demonstrated for the first time the effects of a single, low dose gestational exposure of IgG derived from individual MAU on their offspring's physical and social development. 8) Our results demonstrate abnormal mGluR1/5 signaling in preCGG neurons, which is ameliorated by mGluR1/5 antagonists or augmentation of GABA(A) receptor signaling, and identify allopregnanolone as a candidate therapeutic lead but also implicating mechanisms that could implicate gene x environment interactions. We also published evidence of early mitochondrial impairments in this mouse model (Kaplan et al., 2012). 9) Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g. autism) and neurodegenerative (e.g. Parkinsonism, dementias) disorders. 10) We have identified six subjects carrying an expanded allele on the fragile X gene, which emphasizes the importance of screening for FXS in a population with intellectual disabilities and ASD (Tassone et al., 2012).
Community Outreach and Translation Core
Aim 1:
The COTC has maintained a successful clinical interface between study participants and CCEH investigators, with responsibility for coordinating recruitment and clinical team activities for Project 1, CHARGE-Back and MARBLES, as well as coordination of sample collection and distribution for Project 2 (Immunology) and Cores 3 (Analytical) and 4 (Genetics/Genomics). COTC has also continued to provide outreach and recruitment support to CHARGE, which now has nearly 1700 families enrolled that reflect the ethnic diversity of California.
As of December 2012, there are 238 active MARBLES families with 192 births (195 children of interest; 3 sets of twins). Active families includes those who are pre-pregnant, pregnant, post-partum, and have graduated. To date, a total of 2,102 pre-pregnancy, prenatal, and postpartum visits have been completed. The team has collected 9,755 samples including blood, urine, dust, saliva, hair, meconium and breast milk. From the deliveries, weve collected 176 placentas and 171 cord blood samples.
The retention rate for MARBLES is as follows: Pregnant & post-partum families only: Ever enrolled (completed pregnancy enrollment visit & signed consent): N = 265, Retention Rate = 78% (22% inactive). Inactive (dropped out, no longer eligible, lost to follow-up) = 58.
Dr. Walker is in close contact with families who have concerns regarding pregnancy and delivery; Dr. Hansen and Dr. Ozonoff are in contact with families who have concerns regarding their childrens development and oversee the written feedback provided to families after each developmental assessment visit as well as providing verbal, face-to-face contact with families if needed.
CHARGE-Back completed recruitment and sample collection in January 2010. 145 families participated, with clinical data and biologic samples collected and distributed on 355 individuals (185 CHARGE subjects, 137 mothers and 33 fathers). COTC worked with UCD Clinical and Translational Science Center (CTSC) staff to facilitate sample collection for families and handling and delivery for investigators. Ongoing support in providing feedback on laboratory values to families, both in written form as well as by telephone when values were clinically significant, was provided by COTC staff for laboratory investigators. Dr. Hansen was responsible for this feedback.
COTC staff have participated in community outreach activities at local, regional and state events, and provided updates to Regional Center staff regarding the CCEH, MARBLES and CHARGE studies. The regional centers are critical referral resources for our studies, serving families of children with autism and developmental delay/intellectual disability. Community forums serve as an important recruitment resource for families of children with typical development, and COTC has collaborated with the Center for Excellence in Developmental Disabilities (CEDD) at the MIND Institute on community outreach activities that provide opportunities for recruitment. COTC and CEDD annually reach an estimated audience of about 20,000 at outreach events
Aim 2:
Activities coordinated by the COTC facilitated two-way interaction with the community; COTC representatives maintained attendance at a number of community events, provided numerous presentations about both CHARGE and MARBLES studies, as well as provided information related to environmental hazards for development to diverse audiences in Northern/Central California and nationally, including families, various stakeholder groups, government agencies and media.
Highlights
Summer Institute on Neurodevelopmental Disorders COTC continued to work closely with the UC Davis Center for Excellence in Developmental Disabilities (CEDD) this past year to address issues of underserved populations and access to culturally appropriate information regarding environmental risk factors and the importance of early identification and intervention for autism spectrum disorders and other developmental disabilities. COTC and CEDD, along with the UC Davis MIND Institute, hosted the 8th annual Summer Institute on Neurodevelopmental Disorders. The conference features nationally renowned speakers presenting the latest advances in research, education and therapies for children and adults with autism. This years conference was attended by 262 participants. CCEH Investigator, Dr. Rebecca Schmidt gave a talk titled, Nutrition and neurodevelopment: Importance and potential mechanisms.
California Department of Developmental Services/Regional Centers The COTC is the liaison between the CCEH and the State of California Department of Developmental Services (DDS) and the community based agencies (Regional Centers) through which the State provides services to individuals with disabilities. This past year, the COTC organized a presentation for DDS Director, Terri Delgadillo and others on the DDS leadership team. At the meeting, CCEH investigators Irva Hertz-Picciotto, Robin Hansen, Rebecca Schmidt and Judy Van de Water presented significant research updates. At the local level, the COTC hosted a meeting at the UC Davis MIND Institute for client services directors and case managers from four DDS Regional Centers (Alta, Valley Mountain, North Bay and East Bay) and presented research updates from the CHARGE and MARBLES studies.
Community Outreach/Addressing Health Disparities in Developmental Disabilities The scope of COTC/CEDD outreach to the Latino and Hmong communities has continued to expand. Activities have included sibling workshops for Latino youth, led by bicultural facilitators; parent training videos in English and Spanish; website resources in English and Spanish; and opportunities for training, networking, and technical assistance. We have done outreach to the Spanish-speaking community at conferences such as Fiesta Educativa, one of the largest Spanish language education venues in California, health fairs, community events, the Mexican Consulates Office, the MIND Resource Center, and other venues.
COTC/CEDD has partnered with the Hmong Womens Heritage Association and the United Iu-Mien Community, Inc. to study barriers to quality care among Southeast Asian communities, with the goal of improving health care and access to services for children and adults with developmental disabilities including autism. Based on the findings, project staff and community partners developed a public service campaign aimed at increasing the awareness of developmental disabilities, early identification and services for the Southeast Asian communities.
Community Advisory Council Feedback to and input from the Community Advisory Committee actively continues. Working with CHARGE staff, a newsletter was sent to the CAC, community members and study participants from CHARGE, CHARGE-Back and MARBLES, with updates on recruitment, ethnic diversity, science advances and publications resulting from CCEH research. The newsletter and past materials developed by CCEH are available on the CCEH, CHARGE and MARBLES websites, with many available in Spanish. The CCEH website was completely redesigned in Summer 2011 (www.vetmed.ucdavis.edu/cceh). Additional resources in English and Spanish on autism and other developmental disabilities resources are also on the CEDD website.
Significance:
The feedback provided by COTC staff and investigators regarding study results to regional center staff provides important educational information to them that in turn improves the quality of service provided to families served by staff in those regional centers. The diversity of the subjects recruited through CHARGE, MARBLES and CHARGE-Back, particularly the large number of Spanish speaking families, is of critical importance and attests to COTCs success in community based outreach. Reaching underserved populations for recruitment and dissemination is critical for research studies of all types.
Analytical Core
The results since the last progress report are referenced to 22 publications. The papers have not been cited in previous progress reports.
We continue to provide general analytical support on a walk up basis to all investigators associated with the project. We currently have 3 operational triple quadrapole mass spectrometers. We have replaced the oldest LC triple quadrapole (Waters Ultima) with a new Waters LC-MS/MS which should improve sample sensitivity and throughput. We currently are moving some of our analytical platforms to this new instrument.
Our objectives remain unchanged with work continuing on all of the 4 objectives listed above. The report is referenced back to these objectives.
Objective 1. Establish the metabolic pathways responsible for variations in lipid composition between autistic children and their siblings and between normal and immunologically challenged animal models of autism.
A major effort has been to expand our ability to monitor nutrients as a major component of the total environment of both a mother and infant. One hypothesis for autism is that either foreign compounds in mothers milk or some natural constituent of mothers milk could influence the development of autism spectrum disorders. We have been carrying out fundamental work related to the characterization of human milk with an emphasis on glycoproteins. Of particular note has been the use of high resolution Fourier transform mass spectrometry to characterize glycan content and particularly glycoproteins. As illustrated in a recent PNAS paper, the oligosaccharides primarily from the glycoproteins dramatically alter the microbiota in the infant gut to the point that the major microbes pre weaning are hard to detect post weaning. Thus the oligosaccharides in mothers milk are not there to deliver nutrition to the infant. Neither the infant nor adult intestinal microflora can digest these unique sugar coated proteins. Rather the glycoproteins are produced to select a unique microflora that protects the developing infant gut. The quantitative methods for these glycoproteins and the broader milk proteome and genome are now in place to use to ask if either has an influence on the development of autism.
We have also focused on the development of high sensitivity, quantitative methods of analysis for low abundance oxylipins in blood and urine. These regulatory lipids control a variety of biological processes including inflammation, child birth, blood pressure, pain, cognition and others. We have these platforms operational and they are being used to run samples from autistic children. However, another major lipid class is the structural and nutritional lipids which constitute a large part of our diet. This is particularly important with regard to infant nutrition and mothers milk. The analytical methods for these are established as well and we are working to evaluate their role in health. One of our major efforts has been in the development of methods for the analysis of vitamin D and all of its metabolites (including the biologically active 1,25-dihydroxy D2 and D3). We also have a quantitative method for the analysis of regulatory lipid signaling molecules. In particular this method has been expanded to include signaling molecules in the ω-3 class of lipids. These oxylipins are often more biologically active than their ω-6 counter parts. We have used this method to profile the urine of autistic children. This technology will allow us to monitor supplementation trials of both vitamin D and ω-3 lipids in children. For epidemiological studies it is critical that the resulting assays be highly sensitive and specific. We have developed in the core a new technology for producing transgenic single chain antibodies starting with in vivo immunization of alpaca and llama. This and other immunochemical technologies have worked for several small molecule assays.
Objective 4. Develop new analytical methods for xenobiotics of interest to scientists in the program project.
Initially we focused on developing high throughput methods for the analysis of pesticide exposure in autistic children. These methods include urinary biomarkers for the pyrethroids which are the most commonly used insecticides currently worldwide. Both MS based and immunoassay based methods were developed and are in use by exposure scientists in the project. We failed to find significant exposure in samples from autistic children but the immunoassay method has been used successfully in a worker exposure study. However, our analytical data indicated that in the U.S., pesticide exposure was much lower than many personal care products (both from personal use and from environmental exposure) and far lower again than brominated fire retardants. Thus, we developed a GLC-MS method for the polybrominated biphenyl ethers which has been transferred to a laboratory associated with the project running samples from both autistic children and their mothers. We also have developed a rapid immunoassay for the banned but highly abundant fire retardant PBDE 47. This compound has been banned but our rapid method has permitted survey of furniture stores where we find that PBDE 47 commonly appears in foam products. This was confirmed by GLC-MS studies. We have found that both triclocarban (TCC) and the more commonly used triclosan (TCS) have effects on several enzyme and receptor systems in our studies. TCC is actually a strong anti-inflammatory compound with effects similar to compounds such as Advil. We have developed immunoassays for both TCC and their principle metabolites which are glucuronides. We fund that whole blood is the sample matrix of choice for biomonitoring these materials and particularly triclocarban. These assays and separate LC-MS methods which we developed have been used to monitor human exposure following use in showers with commercial products as well as environmental exposure. We reported several years ago that TCS binds to the ryanodine receptor. Binding to this receptor can led to bioenergetic abnormalities. Recently we published in PNAS that TCS can impair excitation contraction coupling in cardiomyocytes sufficiently to cause death in mice injected with TCS. This and other revelations about this commonly used personal care product may have led Johnson & Johnson to pull all of their triclosan products from the market. Our ICP MS work has led to highly sensitive and relatively routine monitoring of heavy metals in body fluids. This technology has been used to monitor mercury in blood of autistic and non autistic boys and a broad association study of lead, autism, and gene expression.
Significance:
The dramatic decline in the use of triclosan as a personal care product likely is due, at least in part, to the multiple risks we have reported to be associated with its use. The novel derivative which we developed for the analysis of Vitamin D allows the analysis of the biologically active metabolite which is present at very low levels. In the past physicians seldom looked at these levels because the analysis was not routinely available. Our analytical method has now been adopted by several national analytical service laboratories.
The oxylipin profile allows the analysis of over 102 regulatory lipids in the arachidonate cascade. This biochemical pathway is the target of >70% of the worlds pharmaceuticals and is a key regulator of inflammation. Our small initial study failed to show a significant correlation with autism. We are planning a larger study more tightly tied with other meta data including plasma cytokine analysis.
We continue to make and to provide gratis immunoassays for xenobiotics of interest. Through the years we have found the sensitivity of rabbit polyclonal antibodies far exceeds the sensitivity of monoclonals for small molecules. Currently we are making a new type of antibody termed nanobodies in alpaca. We then clone, pan and then express the antibodies in E. coli. We have prepared these cloned recombinant monoclonal antibodies for several pesticide targets and found the resulting assays to be highly sensitive. We are formatting them in a novel biosensor format which is showing very high sensitivity. This technology should be broadly applicable to biosensor designs for a variety of targets.
Finally a major contribution of this core beyond the analytical support provided is the concept of a childs total environment. This environment certainly includes exposure and potential exposure to environmental chemicals, but both the natural and man made compounds in the diet contribute to this total exposome. In order to evaluate the impact of environment on the spectrum of autistic disorders, an appreciation of the total environment will be critical.
Molecular Genomics Core
As in previous years, we have continued the isolated RNA from the participants in these studies. A summary of this work is provided below. In this year of the proposal, PAX tubes have been stored for future RNA isolation.
PAX tubes received between Nov 2011 - Oct 2012 | stored PAX tubes | |||
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# tubes | # of subjects | # tubes stored | # of subjects | |
CHARGE | 105 | 57 | 105 | 57 |
In previous reports we described our recent data on blood genomics in the CHARGE study. In these studies, we have been able to identify genes that are differentially expressed between the general population controls from children with and without regression. The genes meet very strict criteria, greater than 1.5 fold different with FDR correction at P<0.05. These genes are associated with immune related cells and processes and immune related abnormalities have repeatedly been reported in autism spectrum disorders (ASD), including evidence of immune dysregulation and autoimmune phenomena. In new studies, RNA was processed on exon arrays for 30 ASD and 20 typically developing (TD) 2-4 year old boys. Differential alternative splicing (DAS)/ differential exon usage (DEU) was predicted for 477 genes in blood, 16 of which had DAS/DEU predicted in brain. The 477 spliced genes were over-represented in specific pathways including: Natural Killer Cell and NGF implicated in previous studies; mTOR, implicated in ASD associated with Fragile X, PTEN, Neurofibromatosis 1 and Tuberous Sclerosis 1; and in monocyte-related pathways that could relate to microgliosis in ASD brain. Previous studies have shown that Natural Killer cells are differentially expressed in children with autism as compared to typically developing. Five ASD children had alterations of all pathways. The remaining ASD children had alterations of different combinations of these pathways. These data support a role for DAS/DEU and convergence of pathways in ASD.
Figure 4. Above shows unsupervised hierarchical clustering (A) and PCA (B) of the 477 exons predicted to display (DEU) / differential alternative splicing (DAS) in pathways common to a number of ASD individuals. The heatmap in 1A represents adjusted exon expression level (high=red, low=green) of the exon involved in the DAS/DEU. TD subjects denoted in blue; ASD subjects - in grey. The PCA plot in 1B shows separation of the ASD (red spheres) from the TD (blue spheres) subjects. The ellipsoids are drawn at 2 SD around the group centroids.
Figure 5. PCA of the 8 exons from the mTOR Signaling pathway. ASD subjects - red spheres, TD subjects -blue spheres. The ellipsoids are drawn at 2 SD around the group centroids.
Significance:
We feel the above analysis is extremely significant as it demonstrates that RNA expression in blood may be able to identify biomarkers for ASD. The possible differential alternative splicing may point to underlying genetic, pathways, and therapeutic targets. In addition, these differences of splicing likely and expression may lead to development of a blood test for ASD.
Statistical Analysis Core
Aims 1 and 2: Study design, grant collaboration and data analysis support
Grant collaboration: During this time period, Dr. Qi continued to provide support in study design and statistical analysis for many projects, and collaborated with center investigators on new grant proposals including the center renewal, an R01 grant application and an application to Autism Speaks.
Because of the high volume of data available for analysis during this period, substantial analytical effort has been focused on data analysis support for various projects and cores, particularly in analysis of data from the animal model component and on genetics/genomics data. The SC works closely with CCEH Director, Dr. Pessah, and other CCEH investigators, including Drs. Berman, Golub, Lein and Van de Water on various projects.
Analysis for epidemiological studies: The SC continues to provide support on statistical design and analysis in epidemiological studies. This includes
§ analysis to study whether the growth of head circumference is different between children with autism and children with typical development using the CHARGE samples;
§ analysis to study parental characteristics and infantile risk factors for autism using a cohort of Chinese children with and without autism.
Analysis of animal study data: An important area of continuing contribution by the SC is in developing analysis strategies and providing data analysis for animal studies with complex designs. Examples include conducting data analysis
§ to study whether misoprostol exposure early in development causes altered responses in various tasks meant to measure ASD behavior phenotypes in mice. Our findings have been published in PLoS One.
§ to compare the effects of IgG from mothers with an autistic child to that from mothers with a typically developing child using a pregnant mouse model. The findings have been published in Journal of Neuroimmunology.
§ to investigate the effects of alcohol Developing Retinogeniculate Projections in mice.
§ to investigate the effects of PCB 95 on responses in various tasks meant to measure ASD behavior phenotypes in mice.
Analysis of genetics/genomics data: The third area of continuing contribution by the SC is in supporting genetics/genomics and molecular data analysis. This includes
- analysis of mRNA data to compare expression levels between the Fragile X pre-mutation and the control groups for several genes (control, fmr1, GABA, and Gephyrin).
- analysis of cytokines and chemokines data to compare their levels following ex vivo exposure to BDE 49 between children with and without autism for various cytokines and chemokines (eg. IFNgd, IL10d, IL12p40d, IL12p70d, IL13d, IL17d, IL1ad, IL1bd , IL1rad, IL2d, IL4d, IL6d, IL7d, IL8d, IP10d, MCP1d, MIP1ad, MIP1bd, TNFad, eotaxind, sIL2rad).
- analysis of mRNA transcript levels and protein levels of Nrgn, ARC, Spn, Homer1a and Homer1c to investigate their association with the learning and memory of mice.
Thus, the SCs statistical support to the center spans across projects and cores. And the SC continues to provide support in developing statistical analysis strategies to analyze data from complex animal studies, to studying gene-disease associations and the interactions between genes and environment, in analyzing molecular and population-based data analysis, as well as in contributing to the design of new studies.
Aim 3: Linkage of databases across Projects and Cores
Dr. Qi continues to coordinate and respond to all the CCEH statistical needs including advice on complex data types generated. Database organization and design have been established and maintained by individual projects and cores. Dr. Qi attends regularly scheduled core leader/co-leader meetings where database issues are discussed and consultation is provided on analysis of data across different databases resulting from different core projects.
Aim 4: Biostatistics methodology and graduate student mentoring
We continued to encourage and mentor graduate/undergraduate students in Biostatistics/statistics to conduct research motivated by challenging problems from autism studies at the center. For example, Dr. Qi supervised a Ph.D. student in Biostatistics and an undergraduate in the GREAT program to conduct research on nonlinear mixed effects models for longitudinal data, motivated by the longitudinal head circumference data in the CHARGE study. Dr. Qi also supervised and trained a statistical student in the GREAT program to conduct statistical analysis for data from a mouse study.
Significance:
The goal of the SC is to provide researchers at the center with access to statistical expertise necessary for research on the environmental and genetic risk factors that contribute to the incidence and severity of childhood autism. The SC advises on design of studies, linkage of analytic databases across cores and projects, statistical analyses, and mechanisms to allow researchers and decision makers to visualize probable consequences of alternative mechanistic models. Our central role in analyses for the different projects gives us familiarity with each data set and the ability to bring analyses from different disciplines together. Thus the SC fills an important role within the CCEH by providing statistical/analytical expertise and support for data analysis and study design.
Future Activities:
R83329201C001: Environmental Epidemiology
We will continue our studies into the renewal project period.
R83329201C002: Immunological Susceptibility of Autism
We will continue to expand our maternal autoantibody study into a separate RO1 for our work to determine the pathologic significance of the maternal autoantibodies. We will continue our PBDE49 study, which has been demonstrated to be more immunotoxic through our NIEHS/EPA Childrens Center, if renewed.
R83329201C003: Neurodevelopmental Toxicology
We will continue our studies into the renewal project period.
Community Outreach and Translation Core
The COTC will continue to work with the CEDD, CSTC and Center for Reducing Health Disparities to further develop community-based outreach and disseminate information related to early identification, treatment and research on autism spectrum disorders and other developmental disabilities, with a particular emphasis on environmental risk factors affecting developmental outcomes in children. We will continue focus groups in both the Hispanic and Hmong communities to develop culturally relevant materials for awareness and access to resources. COTC/CEDD staff will participate in Fiesta Educativa and Hmong New Year activities as part of our community outreach to underserved communities, and will expand web resources and print materials relevant to these populations.
Analytical Core
A major goal will be to expand the use of our assays in analyzing the body fluids of autistic children, their normal siblings and parents. This will be for both nutrients and for environmental chemicals. We have provided over 60 immunaossays for environmental compounds to the exposure group in the project. We are working to make all of our assays cheaper, faster and more sensitive. For example one of our limitations is that both the vitamin D method and the oxylipin method require 200 ul of serum or plasma to reach the very low levels of the target compounds. These amounts of body fluids are hard to obtain from epidemiological studies. We are working to decrease the amount of sample needed for these studies both by LC-MS and by immunoassay.
Molecular Genomics Core
We plan to continue the collection of RNA from samples collected in the MARBLES and CHARGE-BACK studies (and other biological samples). In addition, we plan to provide genomics applications to each project including gene expression, NGS sequencing, SNP analysis, miRNA analysis, and methylation analysis as funding is available. Through a gift to the MIND, approximately 250 samples will be processed using NextGeneration RNAseq. Moreover, the DNA from the same subjects will be processed on Affymetrix Axiom SNP arrays. We plan to perform copy number analyses using this data, as well as to perform the first expression QTL studies ever performed in autism. In the gene expression arena, we plan to correlate gene expression with presence of autoantibodies in blood, correlate gene expression with ADOS/ADIR scales, language, social, repetitive behaviors; correlate gene expression with head circumference and other variables.
Statistical Analysis Core
The SC will continue to carry out ongoing consultation and collaboration on data collection and statistical support functions, including study design and data analysis. Due to the high volume of data available for analysis, our efforts will be focused on providing data analysis support. We will also continue to pursue development of novel statistical methodologies motivated by CCEH projects, and engage students in the process. The SC will also work closely with other cores and projects to prepare for new grant applications and the transition of the center into a new stage if the center receives funding for the next 5 years. The SC will continue to facilitate development of analytic databases that can link data from multiple studies and that are fully documented for access by statisticians and investigators from all parts of CCEH. We will also assist investigators in developing analytic plans and carrying out analyses linking findings from different studies to build a picture of the neurodevelopmental process that cuts across all the CCEH investigations. We will continue to provide education and mentoring in the biostatistics skills necessary for center researchers, and foster development of externally funded research on statistical methodology relevant to the research goals of the Center.
Journal Articles: 293 Displayed | Download in RIS Format
Other center views: | All 494 publications | 305 publications in selected types | All 293 journal articles |
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Ahn KC, Zhao B, Chen J, Cherednichenko G, Sanmarti E, Denison MS, Lasley B, Pessah IN, Kultz D, Chang DPY, Gee SJ, Hammock BD. In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens. Environmental Health Perspectives 2008;116(9):1203-1210. |
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Ahn KC, Gee SJ, Tsai H-J, Bennett D, Nishioka MG, Blum A, Fishman E, Hammock BD. Immunoassay for monitoring environmental and human exposure to the polybrominated diphenyl ether BDE-47. Environmental Science & Technology 2009;43(20):7784-7790. |
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Ahn KC, Kim H-J, McCoy MR, Gee SJ, Hammock BD. Immunoassays and biosensors for monitoring environmental and human exposure to pyrethroid insecticides. Journal of Agricultural and Food Chemistry 2011;59(7):2792-2802. |
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Ahn KC, Gee SJ, Kim H-J, Aronov PA, Vega H, Krieger RI, Hammock BD. Immunochemical analysis of 3-phenoxybenzoic acid, a biomarker of forestry worker exposure to pyrethroid insecticides. Analytical and Bioanalytical Chemistry 2011;401(4):1285-1293. |
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Ahn KC, Kasagami T, Tsai H-J, Schebb NH, Gee SJ, Hammock BD. An immunoassay to evaluate human/environmental exposure to the antimicrobial triclocarban. Environmental Science & Technology 2012;46(1):374-381. |
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Anderson PJ, Lango J, Carkeet C, Britten A, Krautler B, Hammock BD, Roth JR. One pathway can incorporate either adenine or dimethylbenzimidazole as an α-axial ligand of B12 cofactors in Salmonella enterica. Journal of Bacteriology 2008;190(4):1160-1171. |
R833292 (Final) R829388 (Final) |
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Angkustsiri K, Krakowiak P, Moghaddam B, Wardinsky T, Gardner J, Kalamkarian N, Hertz-Picciotto I, Hansen RL. Minor physical anomalies in children with autism spectrum disorders. Autism 2011;15(6):746-760. |
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Exit |
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Aronov PA, Hall LM , Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels-Alder derivatization and ultra-performance liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry 2008;391(5):1917-1930. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Ashwood P, Kwong C, Hansen R, Hertz-Picciotto I, Croen L, Krakowiak P, Walker W, Pessah IN, Van de Water J. Brief report: plasma leptin levels are elevated in autism: association with early onset phenotype? Journal of Autism and Developmental Disorders 2008;38(1):169-175. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (2006) R829388 (2007) R829388 (Final) |
Exit |
|
Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, Ozonoff S, Pessah IN, Van de Water J. Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. Journal of Neuroimmunology 2008;204(1-2):149-153. |
R833292 (2009) R833292 (Final) |
Exit |
|
Ashwood P, Schauer J, Pessah IN, Van de Water JV. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders. Journal of Neuroimmunology 2009;208(1-2):130-135. |
R833292 (2009) R833292 (Final) |
Exit |
|
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain, Behavior, and Immunity 2011;25(1):40-45. |
R833292 (2010) R833292 (Final) |
Exit Exit Exit |
|
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Altered T cell responses in children with autism. Brain, Behavior, and Immunity 2011;25(5):840-849. |
R833292 (2010) R833292 (Final) |
Exit Exit Exit |
|
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. Journal of Neuroimmunology 2011;232(1-2):196-199. |
R833292 (2011) R833292 (Final) |
Exit |
|
Bannister RA, Pessah IN, Beam KG. The skeletal L-type Ca2+ current is a major contributor to excitation-coupled Ca2+ entry. Journal of General Physiology 2009;133(1):79-91. |
R833292 (2009) R833292 (Final) |
Exit Exit |
|
Barile D, Marotta M, Chu C, Mehra R, Grimm R, Lebrilla CB, German JB. Neutral and acidic oligosaccharides in Holstein-Friesian colostrum during the first 3 days of lactation measured by high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. Journal of Dairy Science 2010;93(9):3940-3949. |
R833292 (Final) |
Exit Exit Exit |
|
Baron CA, Tepper CG, Liu SY, Davis RR, Wang NJ, Schanen NC, Gregg JP. Genomic and functional profiling of duplicated chromosome 15 cell lines reveal regulatory alterations in UBE3A-associated ubiquitin-proteasome pathway processes. Human Molecular Genetics 2006;15(6):853-869. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Baron CA, Liu SY, Hicks C, Gregg JP. Utilization of lymphoblastoid cell lines as a system for the molecular modeling of autism. Journal of Autism and Developmental Disorders 2006;36(8):973-982. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit |
|
Barrientos G, Bose DD, Feng W, Padilla I, Pessah IN. The Na+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate (KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels. Molecular Pharmacology 2009;76(3):560-568. |
R833292 (2009) R833292 (Final) |
Exit Exit |
|
Bauman MD, Lavenex P, Mason WA, Capitanio JP, Amaral DG. The development of social behavior following neonatal amygdala lesions in rhesus monkeys. Journal of Cognitive Neuroscience 2004;16(8):1388-1411. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit |
|
Bennett DH, Wu XM, Teague CH, Lee K, Cassady DL, Ritz B, Hertz-Picciotto I. Passive sampling methods to determine household and personal care product use. Journal of Exposure Science & Environmental Epidemiology 2012;22(2):148-160. |
R833292 (2012) R831540 (Final) |
Exit |
|
Bennett D, Calafat A, Hertz-Piccioltto I, Shin H, Tancredi D. Modeled prenatal exposure to per-and polyfluoroalkyl substances in association with child autism spectrum disorder:A case-control study. Enviornmenal Research 2020;186(109514). |
R833292 (Final) R835432 (Final) |
Exit Exit |
|
Berman RF, Pessah IN, Mouton PR, Mav D, Harry J. Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice. Toxicological Sciences 2008;101(2):294-309. |
R833292 (2008) R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Berman RF, Pessah IN, Mouton PR, Mav D, Harry GJ. Modeling neonatal thimerosal exposure in mice. Toxicological Sciences 2008;103(2):416. |
R833292 (2008) R833292 (Final) R829388 (Final) |
Exit Exit |
|
Braunschweig D, Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J. Autism: maternally derived antibodies specific for fetal brain proteins. NeuroToxicology 2008;29(2):226-231. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J. Behavioral correlates of maternal antibody status among children with autism. Journal of Autism and Developmental Disorders 2012;42(7):1435-1445. |
R833292 (2011) R833292 (Final) |
Exit |
|
Breen M, Garg P, Tang L, Mendonca D, Levy T, Barbosa M, Arnett A, Kurtz-Nelson E, Agolini E, Battaglia A. Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype. American Journal of Human Genetics 2020;107(3):555-563 |
R833292 (Final) |
Exit |
|
Bu B, Ashwood P, Harvey D, King IB, Water JV, Jin LW. Fatty acid compositions of red blood cell phospholipids in children with autism. Prostaglandins, Leukotrienes and Essential Fatty Acids 2006;74(4):215-221. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit |
|
Buchen L. Scientists and autism: when geeks meet. Nature 2011;479(7371):25-27. |
R833292 (2012) |
Exit Exit |
|
Buck Louis GM, Gray LE Jr, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, Sippell W, Abbott DH, Soto A, Tyl RW, Bourguignon JP, Skakkebaek NE, Swan SH, Golub MS, Wabitsch M, Toppari J, Euling SY. Environmental factors and puberty timing: expert panel research needs. Pediatrics 2008;121(Suppl 3):S192-S207. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Buie T, Campbell DB, Fuchs III GJ, Furuta GT, Levy J, Van de Water J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010;125(Suppl 1):S1-S18. |
R833292 (Final) |
Exit Exit Exit |
|
Burke K, Cheng Y, Li B, Petrov A, Joshi P, Berman RF, Reuhl KR, DiCicco-Bloom E. Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E. NeuroToxicology 2006;27(6):970-981. |
R833292 (2009) R833292 (Final) R829388 (2006) R829388 (Final) R829388C005 (2005) R829391 (2006) |
Exit Exit Exit |
|
Cabanlit M, Maitland D, Wilson T, Simon S, Wun T, Gershwin ME, Van de Water J. Polyurethane shape-memory polymers demonstrate functional biocompatibility in vitro. Macromolecular Bioscience 2007;7(1):48-55. |
R833292 (2007) R833292 (Final) |
Exit Exit |
|
Cabanlit M, Wills S, Goines P, Ashwood P, Van de Water J. Brain-specific utoantibodies in the plasma of subjects with autistic spectrum disorder. Annals of the New York Academy of Sciences 2007;1107:92-103. |
R833292 (2007) R833292 (Final) |
Exit |
|
California Dental Association Foundation, American College of Obstetricians and Gynecologists District IX. Oral health during pregnancy and early childhood: evidence-based guidelines for health professionals. Journal of the California Dental Association 2010;38(6):391-403, 405-440. |
R833292 (2010) R833292 (Final) |
Exit |
|
Campbell MA, Golub MS, Iyer P, Kaufman FL, Li LH, Moran Messen F, Morgan JE, Donald JM. Reduced water intake: implications for rodent developmental and reproductive toxicity studies. Birth Defects Research Part B: Developmental and Reproductive Toxicology 2009;86(3):157-175. |
R833292 (2009) R833292 (Final) |
Exit |
|
Cao Z, Hammock BD, McCoy M, Rogawski M, Lein PJ, Pessah IN. Tetramethylenedisulfotetramine alters Ca2+ dynamics in cultured hippocampal neurons: mitigation by NMDA receptor blockade and GABAA receptor-positive modulation. Toxicological Sciences 2012;130(2):362-372. |
R833292 (2012) |
Exit Exit Exit |
|
Careaga M, Van de Water J, Ashwood P. Immune dysfunction in autism: a pathway to treatment. Neurotherapeutics 2010;7(3):283-292. |
R833292 (2011) R833292 (Final) |
Exit Exit |
|
Carkeet C, Dueker SR, Lango J, Buchholz BA, Miller JW, Green R, Hammock BD, Roth JR, Anderson PJ. Human vitamin B12 absorption measurement by accelerator mass spectrometry using specifically labeled 14C-cobalamin. Proceedings of the National Academy of Sciences of the United States of America 2006;103(15):5694-5699. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Chaidez V, Hansen RL, Hertz-Picciotto I. Autism spectrum disorders in Hispanics and non-Hispanics. Autism: The International Journal of Research and Practice 2012;16(4):381-397. |
R833292 (2012) R833292 (Final) |
Exit Exit |
|
Chelu MG, Goonasekera SA, Durham WJ, Tang W, Lueck JD, Riehl J, Pessah IN, Zhang P, Bhattacharjee MB, Dirksen RT, Hamilton SL. Heat-and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse. FASEB Journal 2006;20(2):329-330. |
R833292 (2007) R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit |
|
Chen X, Lin Y; Dang K, Puschner B. Quantification of Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers in Commercial Cows’ Milk from California by Gas Chromatography--Triple Quadruple Mass Spectrometry. <PLosOne 2017;12(1):e0170129. |
R833292 (Final) R829388 (Final) R835432 (2016) R835432 (Final) |
Exit Exit |
|
Chen Y, Tassone F, Berman RF, Hagerman PJ, Hagerman RJ, Willemsen R, Pessah IN. Murine hippocampal neurons expressing Fmr1 gene premutations show early developmental deficits and late degeneration. Human Molecular Genetics 2010;19(1):196-208. |
R833292 (Final) |
Exit Exit Exit |
|
Cherednichenko G, Zhang R, Bannister RA, Timofeyev V, Li N, Fritsch EB, Feng W, Barrientos GC, Schebb NH, Hammock BD, Beam KG, Chiamvimonvat N, Pessah IN. Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle. Proceedings of the National Academy of Sciences of the United States of America 2012;109(35):14158-14163. |
R833292 (2012) R835432 (2013) |
Exit Exit Exit |
|
Chichlowski M, German JB, Lebrilla CB, Mills DA. The influence of milk oligosaccharides on microbiota of infants: opportunities for formulas. Annual Review of Food Science and Technology 2011;2:331-351. |
R833292 (2012) R833292 (Final) |
Exit Exit |
|
Coury DL, Ashwood P, Fasano A, Fuchs G, Geraghty M, Kaul A, Mawe G, Patterson P, Jones NE. Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics 2012;130(Suppl 2):S160-S168. |
R833292 (2012) |
Exit Exit Exit Exit |
|
Croen LA, Goines P, Braunschweig D, Yolken R, Yoshida CK, Grether JK, Fireman B, Kharrazi M, Hansen RL, Van de Water J. Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study. Autism Research 2008;1(2):130-137. |
R833292 (2008) R833292 (Final) |
Exit Exit |
|
Croen LA, Braunschweig D, Haapanen L, Yoshida CK, Fireman B, Grether JK, Kharrazi M, Hansen RL, Ashwood P, Van de Water J. Maternal mid-pregnancy autoantibodies to fetal brain protein: the Early Markers for Autism Study. Biological Psychiatry 2008;64(7):583-588. |
R833292 (2008) R833292 (Final) |
Exit |
|
Crofton KM, Mundy WR, Lein PJ, Bal-Price A, Coecke S, Coecke S, Seiler AEM, Knaut H, Buzanska L, Goldberg A. Developmental neurotoxicity testing: recommendations for developing alternative methods for the screening and prioritization of chemicals. ALTEX 2011;28(1):9-15. |
R833292 (2012) |
Exit Exit |
|
Dai JJ, Lieu L, Rocke D. Dimension reduction for classification with gene expression microarray data. Statistical Applications in Genetics and Molecular Biology 2006;5(1):Article 6 (19 pp.). |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit |
|
Dallas DC, Martin WF, Strum JS, Zivkovic AM, Smilowitz JT, Underwood MA, Affolter M, Lebrilla CB, German JB. N-linked glycan profiling of mature human milk by high-performance microfluidic chip liquid chromatography time-of-flight tandem mass spectrometry. Journal of Agricultural and Food Chemistry 2011;59(8):4255-4263. |
R833292 (2012) R833292 (Final) |
Exit |
|
Davis BB, Morisseau C, Newman JW, Pedersen TL, Hammock BD, Weiss RH. Attenuation of vascular smooth muscle cell proliferation by 1-cyclohexyl-3-dodecyl urea is independent of soluble epoxide hydrolase inhibition. Journal of Pharmacology and Experimental Therapeutics 2006;316(2):815-821. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Denning L, Anderson JA, Davis R, Gregg JP, Kuzdenyi J, Maselli RA. High throughput genetic analysis of congenital myasthenic syndromes using resequencing microarrays. PLoS One 2007;2(9):e918. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Dettmer K, Hanna D, Whetstone P, Hansen R, Hammock BD. Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC-tandem mass spectrometry method to test the opioid excess theory. Analytical and Bioanalytical Chemistry 2007;388(8):1643-1651. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Dettmer K, Aronov PA, Hammock BD. Mass spectrometry-based metabolomics. Mass Spectrometry Reviews 2007;26(1):51-78. |
R833292 (Final) R829388 (Final) |
Exit |
|
Diep AA, Hunsaker MR, Kwock R, Kim K, Willemsen R, Berman RF. Female CGG knock-in mice modeling the fragile X premutation are impaired on a skilled forelimb reaching task. Neurobiology of Learning and Memory 2012;97(2):229-234. |
R833292 (2012) |
Exit |
|
Dodds ED, German JB, Lebrilla CB. Enabling MALDI-FTICR-MS/MS for high-performance proteomics through combination of infrared and collisional activation. Analytical Chemistry 2007;79(24):9547-9556. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Dou J, Middleton L, Zhu Y, Benke K, Feinberg J, Croen L, Hertz-Picciotto I, Newschaffer C, LaSalle J, Fallin D. Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers. INHALATION TOXICOLOGY 2022;15(1):28. |
R833292 (Final) |
Exit Exit |
|
Du XL, Tang Y, Xu H, Lit L, Walker W, Ashwood P, Gregg JP, Sharp FR. Genomic profiles for human peripheral blood T cells, B cells, natural killer cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke, migraine, and Tourette syndrome. Genomics 2006;87(6):693-703. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Eltit JM, Bannister RA, Moua O, Altamirano F, Hopkins PM, Pessah IN, Molinski TF, López JR, Beam KG, Allen PD. Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor. Proceedings of the National Academy of Sciences of the United States of America 2012;109(20):7923-7928. |
R833292 (2012) |
Exit Exit Exit |
|
Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, Hertz-Picciotto I, Van de Water JA, Sharp FR, Ashwood P. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain, Behavior, and Immunity 2009:23(1):124-133. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Current Opinion in Investigational Drugs 2009;10(5):463-473. |
R833292 (Final) |
Exit |
|
Enstrom AM, Onore CE, Van de Water JA, Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain, Behavior, and Immunity 2010;24(1):64-71. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Enstrom A, Onore C, Hertz-Picciotto I, Hansen R, Croen L, Van de Water J, Ashwood P. Detection of IL-17 and IL-23 in plasma samples of children with autism. American Journal of Biochemistry and Biotechnology 2008;4(2):114-120. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit Exit |
|
Enstrom A, Onore C, Tarver A, Hertz-Picciotto I, Hansen R, Croen L, Van de Water J, Ashwood P. Peripheral blood leukocyte production of BDNF following mitogen stimulation in early onset and regressive autism. American Journal of Biochemistry and Biotechnology 2008;4(2):121-129. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit Exit |
|
Enstrom A, Krakowiak P, Onore C, Pessah IN, Hertz-Picciotto I, Hansen RL, Van de Water JA, Ashwood P. Increased IgG4 levels in children with autism disorder. Brain, Behavior, and Immunity 2009;23(3):389-395. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Esteve E, Smida-Rezgui S, Sarkozi S, Szegedi C, Regaya I, Chen L, Altafaj X, Rochat H, Allen P, Pessah IN, Marty I, Sabatier JM, Jona I, De Waard M, Ronjat M. Critical amino acid residues determine the binding affinity and the Ca2+ release efficacy of maurocalcine in skeletal muscle cells. Journal of Biological Chemistry 2003;278(39):37822-37831. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Fang X, Hu S, Watanabe T, Weintraub NL, Snyder GD, Yao J, Liu Y, Shyy JY-J, Hammock BD, Spector AA. Activation of peroxisome proliferator-activated receptor α by substituted urea-derived soluble epoxide hydrolase inhibitors. Journal of Pharmacology and Experimental Therapeutics 2005;314(1):260-270. |
R833292 (Final) R829388 (2006) R829388 (Final) R829389 (Final) |
Exit Exit Exit |
|
Feng W, Tu J, Pouliquin P, Cabrales E, Shen X, Dulhunty A, Worley PF, Allen PD, Pessah IN. Dynamic regulation of ryanodine receptor type 1 (RyR1) channel activity by Homer 1. Cell Calcium 2008;43(3):307-314. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit |
|
Feng W, Barrientos GC, Cherednichenko G, Yang T, Padilla IT, Truong K, Allen PD, Lopez JR, Pessah IN. Functional and biochemical properties of ryanodine receptor type 1 channels from heterozygous R163C malignant hyperthermia-susceptible mice. Molecular Pharmacology 2011;79(3):420-431. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Froehlich JW, Dodds ED, Barboza M, McJimpsey EL, Seipert RR, Francis J, An HJ, Freeman S, German JB, Lebrilla CB. Glycoprotein expression in human milk during lactation. Journal of Agricultural and Food Chemistry 2010;58(10):6440-6448. |
R833292 (Final) |
Exit |
|
German JB, Smilowitz JT, Zivkovic AM. Lipoproteins: when size really matters. Current Opinion in Colloid & Interface Science 2006;11(2-3):171-183. |
R833292 (Final) |
Exit |
|
German JB, Gillies LA, Smilowitz JT, Zivkovic AM, Watkins SM. Lipidomics and lipid profiling in metabolomics. Current Opinion in Lipidology 2007;18(1):66-71. |
R833292 (Final) R829388 (Final) |
Exit |
|
German JB. Dietary lipids from an evolutionary perspective: sources, structures and functions. Maternal & Child Nutrition 2011;7(Suppl 2):2-16. |
R833292 (2012) R833292 (Final) |
Exit |
|
German JB, Zivkovic AM, Dallas DC, Smilowitz JT. Nutrigenomics and personalized diets: what will they mean for food? Annual Review of Food Science and Technology 2011;2:97-123. |
R833292 (2012) R833292 (Final) |
Exit |
|
Gibney MJ, Walsh M, Brennan L, Roche HM, German B, van Ommen B. Metabolomics in human nutrition: opportunities and challenges. American Journal of Clinical Nutrition 2005;82(3):497-503. |
R833292 (Final) R829388 (2006) R829388 (Final) R829388C001 (2005) |
Exit Exit Exit |
|
Giulivi C, Zhang Y-F, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. Mitochondrial dysfunction in autism. JAMA-Journal of the American Medical Association 2010;304(21):2389-2396. |
R833292 (2012) R833292 (Final) |
Exit Exit |
|
Giulivi C, Ross-Inta C, Omanska-Klusek A, Napoli E, Sakaguchi D, Barrientos G, Allen PD, Pessah IN. Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice. Journal of Biological Chemistry 2011;286(1):99-113. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Goines PE, Croen LA, Braunschweig D, Yoshida, CK, Grether J, Hansen R, Kharrazi M, Ashwood P, Van de Water J. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Molecular Autism 2011;2:13. |
R833292 (2011) R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Goines P, Schauer J, Heuer L, Ashwood P, Van de Water J. Beta-2-microglobulin in autism spectrum disorders. American Journal of Biochemistry and Biotechnology 2007;3(2):87-91. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit Exit |
|
Goines P, Van de Water J. The immune system's role in the biology of autism. Current Opinion in Neurology 2010;23(2):111-117. |
R833292 (2009) R833292 (Final) |
Exit |
|
Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, Hansen R, Hertz-Picciotto I, Ashwood P, Van de Water J. Autoantibodies to cerebellum in children with autism associate with behavior. Brain, Behavior, and Immunity 2011;25(3):514-523. |
R833292 (2011) R833292 (Final) |
Exit Exit Exit |
|
Goth SR, Chu RA, Pessah IN. Oxygen tension regulates the in vitro maturation of GM-CSF expanded murine bone marrow dendritic cells by modulating class II MHC expression. Journal of Immunological Methods 2006;308(1-2):179-191. |
R833292 (2007) R833292 (2009) R833292 (Final) R829388 (2006) R829388 (Final) R829388C006 (2005) |
Exit Exit |
|
Goth SR, Chu RA, Gregg JP, Cherednichenko G, Pessah IN. Uncoupling of ATP-mediated calcium signaling and dysregulated interleukin-6 secretion in dendritic cells by nanomolar thimerosal. Environmental Health Perspectives 2006;114(7):1083-1091. |
R833292 (2007) R833292 (Final) R829388 (2006) R829388 (Final) R829388C006 (2005) |
|
|
Greco CM, Navarro CS, Hunsaker MR, Maezawa I, Shuler JF, Tassone F, Delany M, Au JW, Berman RF, Jin L-W, Schumann C, Hagerman PJ, Hagerman RJ. Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome. Molecular Autism 2011;2(1):2 (13 pp.). |
R833292 (2012) |
Exit Exit Exit |
|
Gregg JP, Lit L, Baron CA, Hertz-Picciotto I, Walker W, Davis RA, Croen LA, Ozonoff S, Hansen R, Pessah IN, Sharp FR. Gene expression changes in children with autism. Genomics 2008;91(1):22-29. |
R833292 (2008) R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Hall LM, Kimlin MG, Aronov PA, Hammock BD, Slusser JR, Woodhouse LR, Stephensen CB. Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. Journal of Nutrition 2010;140(3):542-550. |
R833292 (Final) |
Exit Exit Exit |
|
Halladay AK, Amaral D, Aschner M, Bolivar VJ, Bowman A, DiCicco-Bloom E, Hyman SL, Keller F, Lein P, Pessah I, Restifo L, Threadgill DW. Animal models of autism spectrum disorders: information for neurotoxicologists. NeuroToxicology 2009;30(5):811-821. |
R833292 (Final) |
Exit Exit Exit |
|
Hansen RL, Ozonoff S, Krakowiak P, Angkustsiri K, Jones C, Deprey LJ, Le D-N, Croen LA, Hertz-Picciotto I. Regression in autism: prevalence and associated factors in the CHARGE Study. Ambulatory Pediatrics 2008;8(1):25-31. |
R833292 (2008) R833292 (2009) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit Exit |
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Hart L, Thigpen A, Willits N, Lyons L, Hertz-Picciotto I, Hart B. Affectionate Interactions of Cats with Children Having Autism Spectrum Disorder. FRONTIERS IN VETERINARY SCIENCE 2018;5(39). |
R833292 (Final) R829388 (Final) R835432 (Final) |
Exit |
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Herr CE, Dostal M, Ghosh R, Ashwood P, Lipsett M, Pinkerton KE, Sram R, Hertz-Picciotto I. Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths. Environmental Health 2010;9:46. |
R833292 (2010) R833292 (Final) |
Exit Exit |
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Herr CEW, Ghosh R, Dostal M, Skokanova V, Ashwood P, Lipsett M, Joad JP, Pinkerton KE, Yap P-S, Frost JD, Sram R, Hertz-Picciotto I. Exposure to air pollution in critical prenatal time windows and IgE levels in newborns. Pediatric Allergy and Immunology 2011;22(1 Pt 1):75-84. |
R833292 (2011) R833292 (2012) R833292 (Final) |
Exit |
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Hertz-Picciotto I, Charles MJ, James RA, Keller JA, Willman E, Teplin S. In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth. Epidemiology 2005;16(5):648-656. |
R833292 (2007) R833292 (Final) R829388 (2006) R829388 (2007) R829388 (Final) |
Exit |
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Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. The CHARGE Study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environmental Health Perspectives 2006;114(7):1119-1125. |
R833292 (2007) R833292 (Final) R829388 (2006) R829388 (Final) R829388C004 (2005) |
|
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Hertz-Picciotto I, Baker RJ, Yap PS, Dostal M, Joad JP, Lipsett M, Greenfield T, Herr CE, Benes I, Shumway RH, Pinkerton KE, Sram R. Early childhood lower respiratory illness and air pollution. Environmental Health Perspectives 2007;115(10):1510-1518. |
R833292 (2007) R833292 (Final) R829388 (2007) R829388 (Final) R831540 (Final) |
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Hertz-Picciotto I, Park HY, Dostal M, Kocan A, Trnovec T, Sram R. Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. Basic and Clinical Pharmacology and Toxicology 2008;102(2):146-154. |
R833292 (2008) R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Hertz-Picciotto I, Jusko TA, Willman EJ, Baker RJ, Keller JA, Teplin SW, Charles MJ. A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio. Environmental Health 2008;7:37. |
R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009;20(1):84-90. |
R833292 (2009) R833292 (Final) |
Exit Exit |
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Hertz-Picciotto I, Cassady D, Lee K, Bennett DH, Ritz B, Vogt R. Study of Use of Products and Exposure-Related Behaviors (SUPERB):study design, methods, and demographic characteristics of cohorts. Environmental Health 2010;9:54 (14 pp.). |
R833292 (2010) R833292 (Final) R831540 (Final) |
Exit Exit Exit |
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Hertz-Picciotto I, Green PG, Delwiche L, Hansen R, Walker C, Pessah IN. Blood mercury concentrations in CHARGE Study children with and without autism. Environmental Health Perspectives 2010;118(1):161-166. |
R833292 (2009) R833292 (Final) |
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Hertz-Picciotto I, Bergman A, Fangstrom B, Rose M, Krakowiak P, Pessah I, Hansen R, Bennett DH. Polybrominated diphenyl ethers in relation to autism and developmental delay: a case-control study. Environmental Health 2011;10(1):1. |
R833292 (2011) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Heuer LS, Rose M, Ashwood P, Van de Water J. Decreased levels of total immunoglobulin in children with autism are not a result of B cell dysfunction. Journal of Neuroimmunology 2012;251(1-2):94-102. |
R833292 (2012) R833292 (Final) |
Exit |
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Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J. Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Research 2008;1(5):275-283. |
R833292 (2009) R833292 (Final) |
Exit |
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Heuer L, Braunschweig D, Ashwood P, Van de Water J, Campbell DB. Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression. Translational Psychiatry 2011;1:e48. |
R833292 (2011) R833292 (Final) |
Exit Exit Exit |
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Hillyard SL, German JB. Non-essential dietary factors: from test tube to lifespan. Journal of the Science of Food and Agriculture 2007;87(10):1802-1805. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Hillyard SL, German JB. Quantitative lipid analysis and life span of the fat-3 mutant of Caenorhabditis elegans. Journal of Agricultural and Food Chemistry 2009;57(8):3389-3396. |
R833292 (Final) |
Exit |
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Hinde K, German JB. Food in an evolutionary context: insights from mother's milk. Journal of the Science of Food and Agriculture 2012;92(11):2219-2223. |
R833292 (2012) |
Exit |
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Horvathova M, Jahnova E, Palkovicova L, Trnovec T, Hertz-Picciotto I. Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls. Journal of Immunotoxicology 2011;8(4):333-345. |
R833292 (2012) |
Exit |
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Horvathova M, Jahnova E, Palkovicova L, Trnovec T, Hertz-Picciotto I. The kinetics of cell surface receptor expression in children perinatally exposed to polychlorinated biphenyls. Journal of Immunotoxicology 2011;8(4):367-380. |
R833292 (2012) |
Exit |
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Howards PP, Hertz-Picciotto I. Invited commentary: disinfection by-products and pregnancy loss—lessons. American Journal of Epidemiology 2006;164(11):1052-1055. |
R833292 (2007) R833292 (Final) R829388 (2007) R829388 (Final) R831540 (Final) |
Exit Exit Exit |
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Hua S, Nwosu CC, Strum JS, Seipert RR, An HJ, Zivkovic AM, German JB, Lebrilla CB. Site-specific protein glycosylation analysis with glycan isomer differentiation. Analytical and Bioanalytical Chemistry 2012;403(5):1291-1302. |
R833292 (2012) R833292 (Final) |
Exit Exit |
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Huang H, Nishi K, Gee SJ, Hammock BD. Evaluation of chiral α-cyanoesters as general fluorescent substrates for screening enantioselective esterases. Journal of Agricultural and Food Chemistry 2006;54(3):694-699. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit |
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Hwang H-M, Park E-K, Young TM, Hammock BD. Occurrence of endocrine-disrupting chemicals in indoor dust. Science of the Total Environment 2008;404(1):26-35. |
R833292 (Final) |
Exit Exit Exit |
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Inceoglu B, Schmelzer KR, Morisseau C, Jinks SL, Hammock BD. Soluble epoxide hydrolase inhibition reveals novel biological functions of epoxyeicosatrienoic acids (EETs). Prostaglandins & Other Lipid Mediators 2007;82(1-4):42-49. |
R833292 (Final) R829388 (Final) |
Exit |
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Jaubert PJ, Golub MS, Lo YY, Germann SL, Dehoff MH, Worley PF, Kang SH, Schwarz MK, Seeburg PH, Berman RF. Complex, multimodal behavioral profile of the Homer1 knockout mouse. Genes, Brain and Behavior 2007;6(2):141-154. |
R833292 (2007) R833292 (Final) R829388 (2006) R829388 (Final) R829388C005 (2005) |
Exit Exit Exit |
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Jusko TA, Koepsell TD, Baker RJ, Greenfield TA, Willman EJ, Charles MJ, Teplin SW, Checkoway H, Hertz-Picciotto I. Maternal DDT exposures in relation to fetal and 5-year growth. Epidemiology 2006;17(6):692-700. |
R833292 (2007) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit |
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Jusko TA, De Roos AJ, Schwartz SM, Lawrence BP, Palkovicova L, Nemessanyi T, Drobna B, Fabisikova A, Kocan A, Sonneborn D, Jahnova E, Kavanagh TJ, Trnovec T, Hertz-Picciotto I. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age. Environmental Research 2010;110(4):388-395. |
R833292 (2010) R833292 (Final) |
Exit Exit |
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Kania-Korwel I, Barnhart CD, Stamou M, Truong KM, El-Komy MHME, Lein PJ, Veng-Pedersen P, Lehmler H-J. 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and its hydroxylated metabolites are enantiomerically enriched in female mice. Environmental Science & Technology 2012;46(20):11393-11401. |
R833292 (2012) |
Exit |
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Kenet T, Froemke RC, Schreiner CE, Pessah IN, Merzenich MM. Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex. Proceedings of the National Academy of Sciences of the United States of America 2007;104(18):7646-7651. |
R833292 (2007) R833292 (2008) R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
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Kim H-J, Ahn KC, Ma SJ, Gee SJ, Hammock BD. Development of sensitive immunoassays for the detection of the glucuronide conjugate of 3-phenoxybenzyl alcohol, a putative human urinary biomarker for pyrethroid exposure. Journal of Agricultural and Food Chemistry 2007;55(10):3750-3757. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Kim H-J, McCoy M, Gee SJ, Gonzalez-Sapienza GG, Hammock BD. Noncompetitive phage anti-immunocomplex real-time polymerase chain reaction for sensitive detection of small molecules. Analytical Chemistry 2011;83(1):246-253. |
R833292 (2012) R833292 (Final) |
Exit |
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Kim H-J, McCoy MR, Majkova Z, Dechant JE, Gee SJ, Tabares-da Rosa S, Gonzalez-Sapienza GG, Hammock BD. Isolation of alpaca anti-hapten heavy chain single domain antibodies for development of sensitive immunoassay. Analytical Chemistry 2012;84(2):1165-1171. |
R833292 (2012) R833292 (Final) |
Exit |
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Kim H-J, Rossotti MA, Ahn KC, Gonzalez-Sapienza GG, Gee SJ, Musker R, Hammock BD. Development of a noncompetitive phage anti-immunocomplex assay for brominated diphenyl ether 47. Analytical Biochemistry 2010;401(1):38-46. |
R833292 (Final) |
Exit Exit Exit |
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Kim KH, Inan SY, Berman RF, Pessah IN. Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation. Toxicology and Applied Pharmacology 2009;237(2):168-177. |
R833292 (Final) R829388 (Final) R829388C006 (2005) |
Exit Exit Exit |
|
Kim KH, Bose DD, Ghogha A, Riehl J, Zhang R, Barnhart CD, Lein PJ, Pessah IN. Para-and ortho-substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity. Environmental Health Perspectives 2011;119(4):519-526. |
R833292 (2012) R833292 (Final) R829388 (2006) R829388 (Final) |
|
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Kim KH, Pessah IN. Perinatal exposure to environmental polychlorinated biphenyls sensitizes hippocampus to excitotoxicity ex vivo. NeuroToxicology 2011;32(6):981-985. |
R833292 (2011) R833292 (Final) |
Exit Exit Exit |
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Koenig CM, Walker CK, Qi L, Pessah IN, Berman RF. Lack of evidence for neonatal misoprostol neurodevelopmental toxicity in C57BL6/J mice. PLoS ONE 2012;7(6):e38911 (7 pp.). |
R833292 (2012) R833292 (Final) |
Exit Exit |
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Koenig CM, Lango J, Pessah IN, Berman RF. Maternal transfer of BDE-47 to offspring and neurobehavioral development in C57BL/6J mice. Neurotoxicology and Teratology 2012;34(6):571-580. |
R833292 (2012) R835432 (2013) |
Exit Exit Exit |
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Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, Croen LA, Hansen RL. Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study. Journal of Sleep Research 2008;17(2):197-206. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL, Hertz-Picciotto I. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012;129(5):e1121-e1128. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
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Lange MC, Lemay DG, German JB. A multi-ontology framework to guide agriculture and food towards diet and health. Journal of the Science of Food and Agriculture 2007;87(8):1427-1434. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Lee H, Lerno Jr. LA, Choe Y, Chu CS, Gillies LA, Grimm R, Lebrilla CB, German JB. Multiple precursor ion scanning of gangliosides and sulfatides with a reversed-phase microfluidic chip and quadrupole time-of-flight mass spectrometry. Analytical Chemistry 2012;84(14):5905-5912. |
R833292 (2012) |
Exit |
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Lein PJ, Barnhart CD, Pessah IN. Acute hippocampal slice preparation and hippocampal slice cultures. Methods in Molecular Biology 2011;758:115-134. |
R833292 (Final) |
Exit |
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Lemay DG, Neville MC, Rudolph MC, Pollard KS, German JB. Gene regulatory networks in lactation: identification of global principles using bioinformatics. BMC Systems Biology 2007;1:56 (24 pp.). |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Lemay DG, Zivkovic AM, German JB. Building the bridges to bioinformatics in nutrition research. American Journal of Clinical Nutrition 2007;86(5):1261-1269. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Lemay DG, Lynn DJ, Martin WF, Neville MC, Casey TM, Rincon G, Kriventseva EV, Barris WC, Hinrichs AS, Molenaar AJ, Pollard KS, Maqbool NJ, Singh K, Murney R, Zdobnov EM, Tellam RL, Medrano JF, German JB, Rijnkels M. The bovine lactation genome: insights into the evolution of mammalian milk. Genome Biology 2009;10(4):R43 (18 pp.). |
R833292 (Final) |
Exit Exit Exit |
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Li L. Survival prediction of diffuse large-B-cell lymphoma based on both clinical and gene expression information. Bioinformatics 2006;22(4):466-471. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
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Li N, Liu J-Y, Timofeyev V, Qiu H, Hwang SH, Tuteja D, Lu L, Yang J, Mochida H, Low R, Hammock BD, Chiamvimonvat N. Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: insight gained using metabolomic approaches. Journal of Molecular and Cellular Cardiology 2009;47(6):835-845. |
R833292 (Final) |
Exit |
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Li N, Liu J-Y, Qiu H, Harris TR, Sirish P, Hammock BD, Chiamvimonvat N. Use of metabolomic profiling in the study of arachidonic acid metabolism in cardiovascular disease. Congestive Heart Failure 2011;17(1):42-46. |
R833292 (Final) |
Exit Exit Exit |
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Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah IN, Hagerman PJ. Signaling defects in iPSC-derived fragile X premutation neurons. Human Molecular Genetics 2012;21(17):3795-3805. |
R833292 (2012) R835432 (2013) |
Exit Exit Exit |
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Lyall K, Song L, Botteron K, Croen L, Dager S, Fallin M, Hazlett H, Kauffman E, Landar R, Ladd-Acosta C. The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism. AUTISM RESEARCH 2020;. |
R833292 (Final) |
Exit |
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Magby JP, Neal AP, Atchison WD, Pessah IP, Shafer TJ. Channelopathies: summary of the hot topic keynotes session. NeuroToxicology 2011;32(5):661-665. |
R833292 (2011) R833292 (Final) |
Exit Exit Exit |
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Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain, Behavior, and Immunity 2008;22(6):806-816. |
R833292 (2008) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Masuno MN, Pessah IN, Olmstead MM, Molinski TF. Simplified cyclic analogues of bastadin-5. Structure-activity relationships for modulation of the RyR1/FKBP12 Ca2+ channel complex. Journal of Medicinal Chemistry 2006;49(15):4497-4511. |
R833292 (2007) R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
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McCanlies EC, Fekedulegn D, Mnatsakanova A, Burchfiel CM, Sanderson WT, Charles LE, Hertz-Picciotto I. Parental occupational exposures and autism spectrum disorder. Journal of Autism and Developmental Disorders 2012;42(11):2323-2334. |
R833292 (2012) R833292 (Final) R836159 (2019) |
Exit |
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Merin N, Young GS, Ozonoff S, Rogers SJ. Visual fixation patterns during reciprocal social interaction distinguish a subgroup of 6-month-old infants at-risk for autism from comparison infants. Journal of Autism and Developmental Disorders 2007;37(1):108-121. |
R833292 (2007) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit |
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Mitchell MM, Woods R, Chi L-H, Schmidt RJ, Pessah IN, Kostyniak PJ, LaSalle JM. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environmental and Molecular Mutagenesis 2012;53(8):589-598. |
R833292 (2012) R833292 (Final) R835432 (2013) |
Exit Exit Exit |
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Morisseau C, Merzlikin O, Lin A, He G, Feng W, Padilla I, Denison MS, Pessah IN, Hammock BD. Toxicology in the fast lane: application of high-throughput bioassays to detect modulation of key enzymes and receptors. Environmental Health Perspectives 2009;117(12):1867-1872. |
R833292 (2009) R833292 (Final) |
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Nadig AS, Ozonoff S, Young GS, Rozga A, Sigman M, Rogers SJ. A prospective study of response to name in infants at risk for autism. Archives of Pediatrics & Adolescent Medicine 2007;161(4):378-383. |
R833292 (2007) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit Exit |
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Nagarajan RP, Patzel KA, Martin M, Yasui DH, Swanberg SE, Hertz-Picciotto I, Hansen RL, Van de Water J, Pessah IN, Jiang R, Robinson WP, LaSalle JM. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Research 2008;1(3):169-178. |
R833292 (2008) R833292 (2009) R833292 (Final) |
Exit |
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Newman JW, Kaysen GA, Hammock BD, Shearer GC. Proteinuria increases oxylipid concentrations in VLDL and HDL, but not LDL particles in the rat. Journal of Lipid Research 2007;48(8):1792-1800. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Newschaffer CJ, Croen LA, Fallin MD, Hertz-Picciotto I, Nguyen DV, Lee NL, Berry CA, Farzadegan H, Hess HN, Landa RJ, Levy SE, Massolo ML, Meyerer SC, Mohammed SM, Oliver MC, Ozonoff S, Pandey J, Schroeder A, Shedd-Wise KM. Infant siblings and the investigation of autism risk factors. Journal of Neurodevelopmental Disorders 2012;4(1):7 (16 pp.). |
R833292 (2012) |
Full Text PDF Exit Abstract & Full Text HTML Exit |
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Nguyen DV, Senturk D. Distortion diagnostics for covariate-adjusted regression: graphical techniques based on local linear modeling. Journal of Data Science 2007;5(4):471-490. |
R833292 (Final) R829388 (Final) |
Exit Exit |
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Nguyen DV, Senturk D, Carroll RJ. Covariate-adjusted linear mixed effects model with an application to longitudinal data. Journal of Nonparametric Statistics 20(6):459-481. |
R833292 (Final) |
Exit |
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Ninonuevo MR, Park Y, Yin H, Zhang J, Ward RE, Clowers BH, German JB, Freeman SL, Killeen K, Grimm R, Lebrilla CB. A strategy for annotating the human milk glycome. Journal of Agricultural and Food Chemistry 2006;54(20):7471-7480. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Ninonuevo MR, Ward RE, LoCascio RG, German JB, Freeman SL, Barboza M, Mills DA, Lebrilla CB. Methods for the quantitation of human milk oligosaccharides in bacterial fermentation by mass spectometry. Analytical Biochemistry 2007;361(1):15-23. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Oberbauer AM, German JB, Murray JD. Growth hormone enhances arachidonic acid metabolites in a growth hormone transgenic mouse. Lipids 2011;46(6):495-504. |
R833292 (2012) R833292 (Final) |
Exit |
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Oh J, Bennett D, Calafat A, Tancredi D, Roa D, Schmidt R, Hertz-Picciotto I, Shin H. Prenatal exposure to per-and polyfluoroalkyl substances in association with autism spectrum disorder in the MARBLES study. Enviornmenal International 2020;(106328). |
R833292 (Final) R829388 (Final) R829389 (Final) R835432 (Final) |
Exit Exit |
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Oh J, Bennett D, Tancredi D, Calafat A, Schmidt R, Hertz-Picciotto I, Shin H. Longitudinal Changes in Maternal Serum Concentrations of Per-and Polyfluoroalkyl Substances from Pregnancy to Two Years Postpartum. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2022;56(16):11449-11459. |
R833292 (Final) |
Exit Exit |
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Onore CE, Nordahl CW, Young GS, Van de Water JA, Rogers SJ, P Ashwood P. Levels of soluble adhesion molecules PECAM-1 and P-selectin are decreased in children with autism spectrum disorder. Biological Psychiatry 2012;72(12):1020-1025. |
R833292 (2012) |
Exit |
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Onore C, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Van de Water J, Ashwood P. Decreased cellular IL-23 but not IL-17 production in children with autism spectrum disorders. Journal of Neuroimmunology 2009;216(1-2):126-129. |
R833292 (2009) R833292 (2010) R833292 (Final) |
Exit |
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Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain, Behavior, and Immunity 2012;26(3):383-392. |
R833292 (2011) R833292 (Final) |
Exit Exit |
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Ostrovskaya O, Goyal R, Osman N, McAllister CE, Pessah IN, Hume JR, Wilson SM. Inhibition of ryanodine receptors by 4-(2-aminopropyl)-3,5-dichloro-N,N-dimethylaniline (FLA 365) in canine pulmonary arterial smooth muscle cells. Journal of Pharmacology and Experimental Therapeutics 2007;323(1):381-390. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
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Ozonoff S, Young GS, Goldring S, Greiss-Hess L, Herrera AM, Steele J, Macari S, Hepburn S, Rogers SJ. Gross motor development, movement abnormalities, and early identification of autism. Journal of Autism and Developmental Disorders 2008;38(4):644-656. |
R833292 (2007) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit |
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Ozonoff S, Heung K, Byrd R, Hansen R, Hertz-Picciotto I. The onset of autism: patterns of symptom emergence in the first years of life. Autism Research 2008;1(6):320-328. |
R833292 (2009) R833292 (Final) |
Exit |
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Ozonoff S, Iosif A-M, Young GS, Hepburn S, Thompson M, Colombi C, Cook IC, Werner E, Goldring S, Baguio F, Rogers SJ. Onset patterns in autism: correspondence between home video and parent report. Journal of the American Academy of Child & Adolescent Psychiatry 2011;50(8):796-806.e1. |
R833292 (2012) |
Exit |
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Ozonoff S. The first cut is the deepest: why do the reported effects of treatments decline over trials? Journal of Child Psychology and Psychiatry 2011;52(7):729-730 (editorial). |
R833292 (2012) |
Exit Exit Exit |
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Palkovicova L, Ursinyova M, Masanova V, Yu Z, Hertz-Picciotto I. Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. Journal of Exposure Science & Environmental Epidemiology 2008;18(3):326-331. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (2007) R829388 (Final) |
Exit Exit |
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Parenti M, Schmidt R, Ozonoff S, Shin H, Tancredi D, Daniel J, Krakowiak P, Hertz-Picciotto I, Walker C, SLupsky C. Maternal Serum and Placental Metabolomes in Association with Prenatal Phthalate Exposure and Neurodevelopmental Outcomes in the MARBLES Cohort. METABOLITES 2022;12(9):829. |
R833292 (Final) R829388 (Final) |
Exit Exit |
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Park HY, Hertz-Picciotto I, Sovcikova E, Kocan A, Drobna B, Trnovec T. Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs) by chemical structure and activity: a birth cohort study. Environmental Health 2010;9:51. |
R833292 (2010) R833292 (Final) |
Exit Exit Exit |
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Park H-Y, Hertz-Picciotto I, Petrik J, Palkovicova L, Kocan A, Trnovec T. Prenatal PCB exposure and thymus size at birth in neonates in Eastern Slovakia. Environmental Health Perspectives 2008;116(1):104-109. |
R833292 (Final) R829388 (Final) |
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Park H-Y, Park J-S, Sovcikova E, Kocan A, Linderholm L, Bergman A, Trnovec T, Hertz-Picciotto I. Exposure to hydroxylated polychlorinated biphenyls (OH-PCBs) in the prenatal period and subsequent neurodevelopment in Eastern Slovakia. Environmental Health Perspectives 2009;117(10):1600-1606. |
R833292 (Final) |
|
|
Park J-S, Bergman A, Linderholm L, Athanasiadou M, Kocan A, Petrik J, Drobna B, Trnovec T, Charles MJ, Hertz-Picciotto I. Placental transfer of polychlorinated biphenyls, their hydroxylated metabolites and pentachlorophenol in pregnant women from eastern Slovakia. Chemosphere 2008;70(9):1676-1684. |
R833292 (Final) |
Exit Exit Exit |
|
Paul R, Pessah IN, Gane L, Ono M, Hagerman PJ, Brunberg JA, Tassone F, Bourgeois JA, Adams PE, Nguyen DV, Hagerman R. Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins. Neurotoxicology 2010;31(4):399-402. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Pessah IN, Hansen LG, Albertson TE, Garner CE, Ta TA, Do Z, Kim KH, Wong PW. Structure-activity relationship for noncoplanar polychlorinated biphenyl congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1). Chemical Research in Toxicology 2006;19(1):92-101. |
R833292 (2007) R833292 (2009) R833292 (Final) R829388 (2006) R829388 (Final) R829388C006 (2005) |
Exit Exit Exit |
|
Pessah IN, Seegal RF, Lein PJ, LaSalle J, Yee BK, Van de Water J, Berman RF. Immunologic and neurodevelopmental susceptibilities of autism. NeuroToxicology 2008;29(3):532-545. |
R833292 (2008) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Pessah IN, Lehmler HJ, Robertson LW, Perez CF, Cabrales E, Bose DD, Feng W. Enantiomeric specificity of (-)-2,2',3,3',6,6'-hexachlorobiphenyl toward ryanodine receptor types 1 and 2. Chemical Research in Toxicology 2009;22(1):201-207. |
R833292 (Final) |
Exit |
|
Pessah IN, Cherednichenko G, Lein PJ. Minding the calcium store: ryanodine receptor activation as a convergent mechanism of PCB toxicity. Pharmacology & Therapeutics 2010;125(2):260-285. |
R833292 (2009) R833292 (Final) R829388 (Final) |
Exit Exit |
|
Pessah IN, Truong K. Additional Safety Assessments Needed for Diamide Insecticides.STOXICOLOGICAL SCIENCES 2019:170(2):509-524 |
R833292 (Final) |
Exit Exit |
|
Philippat C, Bennett DH, Krakowiak P, Rose M, Hwang HM, Hertz-Picciotto I. Phthalate concentrations in house dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study. Environmental Health 2015;14:56 (10 pp.). |
R833292 (Final) R829388 (Final) R835432 (2014) |
Exit Exit Exit |
|
Phimister AJ, Lango J, Lee EH, Ernst-Russell MA, Takeshima H, Ma J, Allen PD, Pessah IN. Conformation-dependent stability of junctophilin 1 (JP1) and ryanodine receptor type 1 (RyR1) channel complex is mediated by their hyper-reactive thiols. Journal of Biological Chemistry 2007;282(12):8667-8677. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Qi L, Wang Y-F, He Y. A comparison of multiple imputation and fully augmented weighted estimators for Cox regression with missing covariates. Statistics in Medicine 2010;29(25):2592-2604. |
R833292 (Final) |
Exit |
|
Qiu H, Li N, Liu J-Y, Harris TR, Hammock BD, Chiamvimonvat N. Soluble epoxide hydrolase inhibitors and heart failure. Cardiovascular Therapeutics 2011;29(2):99-111. |
R833292 (Final) |
Exit Exit Exit |
|
Rose D, Ashwood P. Rapid Communication:Plasma Interleukin-35 in Children with Autism . Brain Sciences2019;9(7):152;. |
R833292 (Final) |
Exit Exit |
|
Rose M, Bennett DH, Bergman A, Fangstrom B, Pessah IN, Hertz-Picciotto I. PBDEs in 2-5 year-old children from California and associations with diet and indoor environment. Environmental Science & Technology 2010;44(7):2648-2653. |
R833292 (2009) R833292 (2010) R833292 (Final) |
Exit |
|
Rossi CC, Van de Water J, Rogers SJ, Amaral DG. Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders. Brain, Behavior, and Immunity 2011;25(6):1123-1135. |
R833292 (2011) R833292 (2012) R833292 (Final) |
Exit Exit |
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Samso M, Feng W, Pessah IN, Allen PD. Coordinated movement of cytoplasmic and transmembrane domains of RyR1 upon gating. PLoS Biology 2009;7(4):e85 (16 pp.). |
R833292 (2009) R833292 (Final) |
Exit Exit |
|
Schmelzer KR, Inceoglu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, Hammock BD. Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proceedings of the National Academy of Sciences of the United States of America 2006;103(37):13646-13651. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Schmelzer KR, Wheelock AM, Dettmer K, Morin D, Hammock BD. The role of inflammatory mediators in the synergistic toxicity of ozone and 1-nitronaphthalene in rat airways. Environmental Health Perspectives 2006;114(9):1354-1360. |
R833292 (Final) R829388 (Final) |
|
|
Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 2011;22(4):476-485. |
R833292 (2011) R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. American Journal of Clinical Nutrition 2012;96(1):80-89. |
R833292 (2009) R833292 (2012) R833292 (Final) R829388 (Final) |
Exit Exit |
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Schmidt RJ, Tancredi DJ, Krakowiak P, Hansen RL, Ozonoff S. Maternal intake of supplemental iron and risk of autism spectrum disorder. American Journal of Epidemiology 2014;180(9):890-900. |
R833292 (Final) R829388 (Final) R835432 (2014) |
Exit Exit Exit |
|
Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Sconberg JL, Schmidt LC, Volk HE, Tassone F. Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. Early Human Development 2015;91(8):483-489. |
R833292 (Final) R829388 (Final) R835432 (2014) |
Exit Exit Exit |
|
Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, Ozonoff S, Ma CC, McCanlies EC, Bennett DH, Hertz-Picciotto I, Tancredi DJ, Volk HE. Combined prenatal pesticide exposure and folic acid intake in relation to autism spectrum disorder. Environmental Health Perspectives 2017;125(9):097007 (12 pp.). |
R833292 (Final) R829388 (Final) R835432 (2017) |
|
|
Schmidt RJ, Niu Q, Eyles DW, Hansen RL, Iosif, A. Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study. Autism Research 2019;12(6):976-988. |
R833292 (Final) |
Exit |
|
Senturk D, Nguyen DV. Partial covariate adjusted regression. Journal of Statistical Planning and Inference 2009;139(2):454-468. |
R833292 (Final) |
Exit Exit Exit |
|
Shearer GC, Newman JW, Hammock BD, Kaysen GA. Graded effects of proteinuria on HDL structure in nephrotic rats. Journal of the American Society of Nephrology 2005;16(5):1309-1319. |
R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Shelton JF, Tancredi DJ, Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Research 2010;3(1):30-39. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Shelton JF, Hertz-Picciotto I, Pessah IN. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environmental Health Perspectives 2012;120(7):944-951. |
R833292 (2012) R833292 (Final) R835432 (2013) |
|
|
Smilowitz JT, Dillard CJ, German JB. Milk beyond essential nutrients: the metabolic food. Australian Journal of Dairy Technology 2005;60(2):77-83. |
R833292 (Final) R829388 (Final) |
Exit Exit |
|
Sonneborn D, Park HY, Petrik J, Kocan A, Palkovicova L, Trnovec T, Nguyen D, Hertz-Picciotto I. Prenatal polychlorinated biphenyl exposures in eastern Slovakia modify effects of social factors on birthweight. Paediatric and Perinatal Epidemiology 2008;22(3):202-213. |
R833292 (Final) R829388 (Final) R831540 (Final) |
Exit Exit |
|
Sonneborn D, Park HY, Babinska K, Palkovicova L, Trnovec T, Kocan A, Nguyen DV, Hertz-Picciotto I. Serum PCB concentrations in relation to locally produced food items in eastern Slovakia. Journal of Exposure Science & Environmental Epidemiology 2008;18(6):581-587. |
R833292 (2009) R833292 (Final) R829388 (Final) R831540 (Final) |
Exit Exit |
|
Sotelo-Orizco J, Schmidt J, Slupsky C, Hertz-Picciotto I. Investigating the Urinary Metabolome in the First Year of Life and Its Association with Later Diagnosis of Autism Spectrum Disorder or Non-Typical Neurodevelopment in the MARBLES Study. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCE 2023;24(11):9454. |
R833292 (Final) |
Exit |
|
Stamova BS, Apperson M, Walker WL, Tian Y, Xu H, Adamczy P, Zhan X, Liu D-Z, Ander BP, Liao IH, Gregg JP, Turner RJ, Jickling GC, Lit L, Sharp FR. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood. BMC Medical Genomics 2009;2:49. |
R833292 (Final) |
Exit Exit Exit |
|
Stamova BS, Tian Y, Nordahl CW, Shen MD, Rogers S, Amaral DG, Sharp FR. Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders. Molecular Autism 2013;4:30 (16 pp.). |
R833292 (2012) |
Exit Exit |
|
Stamova B, Green PG, Tian Y, Hertz-Picciotto I, Pessah IN, Hansen R, Yang X, Teng J, Gregg JP, Ashwood P, Van de Water J, Sharp FR. Correlations between gene expression and mercury levels in blood of boys with and without autism. Neurotoxicity Research 2011;19(1):31-48. |
R833292 (2009) R833292 (2010) R833292 (Final) |
Exit Exit Exit |
|
Sundekilde UK, Barile D, Meyrand M, Poulsen NA, Larsen LB, Lebrilla CB, German JB, Bertram HC. Natural variability in bovine milk oligosaccharides from Danish Jersey and Holstein-Friesian breeds. Journal of Agricultural and Food Chemistry 2012;60(24):6188-6196. |
R833292 (2012) |
Exit |
|
Ta TA, Feng W, Molinski TF, Pessah IN. Hydroxylated xestospongins block inositol-1,4,5-trisphosphate-induced Ca2+ release and sensitive Ca2+-induced Ca2+ release mediated by ryanodine receptors. Molecular Pharmacology 2006;69(2):532-538. |
R833292 (Final) R829388 (2006) R829388 (Final) R829388C006 (2005) |
Exit Exit Exit |
|
Ta TA, Pessah IN. Ryanodine receptor type 1 (RyR1) possessing malignant hyperthermia mutation R615C exhibits heightened sensitivity to dysregulation by non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95). NeuroToxicology 2007;28(4):770-779. |
R833292 (2007) R833292 (2008) R833292 (2009) R833292 (Final) R829388 (2006) R829388 (Final) |
Exit Exit Exit |
|
Ta TA, Koenig CM, Golub MS, Pessah IN, Qi L, Aronov PA, Berman RF. Bioaccumulation and behavioral effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in perinatally exposed mice. Neurotoxicology and Teratology 2011;33(3):393-404. |
R833292 (2011) R833292 (Final) |
Exit Exit Exit |
|
Tabares-da Rosa S, Rossotti M, Carleiza C, Carrion F, Pritsch O, Ahn KC, Last JA, Hammock BD, Gonzalez-Sapienza G. Competitive selection from single domain antibody libraries allows isolation of high-affinity antihapten antibodies that are not favored in the llama immune response. Analytical Chemistry 2011;83(18):7213-7220. |
R833292 (2012) |
Exit |
|
Tassone F, Qi L, Zhang W, Hansen RL, Pessah IN, Hertz-Picciotto I. MAOA, DΒH and SLC6A4 variants in CHARGE: a case-control study of autism spectrum disorders. Autism Research 2011;4(4):250-261. |
R833292 (2011) R833292 (Final) |
Exit |
|
Tian Y, Green PG, Stamova B, Hertz-Picciotto I, Pessah IN, Hansen R, Yang X, Gregg JP, Ashwood P, Jickling G, Van de Water J, Sharp FR. Correlations of gene expression with blood lead levels in children with autism compared to typically developing controls. Neurotoxicity Research 2011;19(1):1-13. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Trnovec T, Dedík L, Jusko TA, Lancz K, Palkovicova L, Kocan A, Sovcikova E, Wimmerova S, Tihanyi J, Patayova H, Hertz-Picciotto I. Assessment of exposure to PCB 153 from breast feeding and normal food intake in individual children using a system approach model. Chemosphere 2011;85(11):1687-1693. |
R833292 (2012) |
Exit Exit Exit |
|
Ulu A, Davis BB, Tsai H-J, Kim I-H, Morisseau C, Inceoglu B, Fiehn O, Hammock BD, Weiss RH. Soluble epoxide hydrolase inhibitors reduce the development of atherosclerosis in apolipoprotein E-knockout mouse model. Journal of Cardiovascular Pharmacology 2008;52(4):314-323. |
R833292 (Final) |
Exit Exit Exit |
|
Van Meter KC, Christiansen LE, Hertz-Picciotto I, Azari R, Carpenter TE. A procedure to characterize geographic distributions of rare disorders in cohorts. International Journal of Health Geographics 2008;7:26. |
R833292 (Final) |
Exit Exit Exit |
|
Van Meter KC, Christiansen LE, Delwiche, LD, Azari R, Carpenter TE, Hertz-Picciotto I. Geographic distribution of autism in California: a retrospective birth cohort analysis. Autism Research 2010;3(1):19-29. |
R833292 (2009) R833292 (Final) |
Exit |
|
Verner MA, Sonneborn D, Lancz K, Muckle G, Ayotte P, Dewailly E, Kocan A, Palkovicova L, Trnovec T, Haddad S, Hertz-Picciotto I, Eggesbo M. Toxicokinetic modeling of persistent organic pollutant levels in blood from birth to 45 months of age in longitudinal birth cohort studies. Environmental Health Perspectives 2013;121(1):131-137. |
R833292 (2012) |
|
|
Vogel CFA, Goth SR, Dong B, Pessah IN, Matsumura F. Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase. Biochemical and Biophysical Research Communications 2008;375(3):331-335. |
R833292 (Final) |
Exit Exit Exit |
|
Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE Study. Environmental Health Perspectives 2011;119(6):873-877. |
R833292 (2011) R833292 (Final) |
|
|
Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Applied and Environmental Microbiology 2006;72(6):4497-4499. |
R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentability of human milk oligosaccharides by several strains of bifidobacteria. Molecular Nutrition & Food Research 2007;51(11):1398-1405. |
R833292 (Final) R829388 (Final) |
Exit |
|
Wayman GA, Bose DD, Yang D, Lesiak A, Bruun D, Impey S, Ledoux V, Pessah IN, Lein PJ. PCB 95 modulates calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environmental Health Perspectives 2012;120(7):1003-1009. |
R833292 (2012) R833292 (Final) |
|
|
Wayman GA, Yang D, Bose DD, Lesiak A, Ledoux V, Bruun D, Pessah IN, Lein PJ. PCB-95 promotes dendritic growth via ryanodine receptor-dependent mechanisms. Environmental Health Perspectives 2012;120(7):997-1002. |
R833292 (2012) R833292 (Final) R835432 (2013) |
|
|
Wiest MM, German JB, Harvey DJ, Watkins SM, Hertz-Picciotto I. Plasma fatty acid profiles in autism: a case-control study. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2009;80(4):221-227. |
R833292 (2009) R833292 (Final) |
Exit Exit |
|
Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J. Autoantibodies in autism spectrum disorders (ASD). Annals of the New York Academy of Sciences 2007;1107:79-91. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit Exit |
|
Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral DG, Van de Water J. Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain, Behavior, and Immunity 2009;23(1):64-74. |
R833292 (2008) R833292 (Final) |
Exit Exit Exit |
|
Wills S, Rossi CC, Bennett J, Martinez-Cerdeno V, Ashwood P, Amaral DG, Van de Water J. Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism. Molecular Autism 2011;2:5. |
R833292 (2011) R833292 (Final) |
Exit Exit Exit |
|
Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH, Chi LH, Kostyniak PJ, Pessah IN, Berman RF, LaSalle JM. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Human Molecular Genetics 2012;21(11):2399-2411. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Wu XM, Bennett DH, Ritz B, Frost J, Cassady D, Lee K, Hertz-Picciotto I. Residential insecticide usage in northern California homes with young children. Journal of Exposure Science & Environmental Epidemiology 2011;21(4):427-436. |
R833292 (2012) R831540 (Final) |
Exit Exit |
|
Wu XM, Bennett DH, Lee K, Cassady DL, Ritz B, Hertz-Picciotto I. Feasibility of using web surveys to collect time-activity data. Journal of Exposure Science & Environmental Epidemiology 2012;22(2):116-125. |
R833292 (2012) R831540 (Final) |
Exit Exit |
|
Wu X, Apte MG, Maddalena R, Bennett DH. Volatile organic compounds in small- and medium-sized commercial buildings in California. Environmental Science & Technology 2011;45(20):9075-9083. |
R833292 (2012) |
Exit |
|
Wu X, Bennett DH, Lee K, Cassady DL, Ritz B, Hertz-Picciotto I. Longitudinal variability of time-location/activity patterns of population at different ages:a longitudinal study in California. Environmental Health 2011;10:80 (15 pp.). |
R833292 (2012) R831540 (Final) |
Exit Exit Exit |
|
Yakes EA, Arsenault JE, Islam MM, Hossain MB, Ahmed T, German JB, Gillies LA, Rahman AS, Drake C, Jamil KM, Lewis BL, Brown KH. Intakes and breast-milk concentrations of essential fatty acids are low among Bangladeshi women with 24-48-month-old children. British Journal of Nutrition 2011;105(11):1660-1670. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Yakes EA, Arsenault JE, Islam MM, Ahmed T, German JB, Drake C, Hossain MB, Lewis BL, Rahman AS, Jamil KM, Brown KH. Dietary intake of polyunsaturated fatty acids among breast-feeding and non-breast-feeding 24- to 48-month-old children in Bangladesh. Journal of Pediatric Gastroenterology and Nutrition 2011;52(3):351-359. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Yang D, Kim KH, Phimister AV, Bachstetter AD, Ward TR, Stackman RW, Mervis RF, Wisniewski AB, Klein SL, Kodavanti PRS, Anderson KA, Wayman G, Pessah IN, Lein PJ. Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. Environmental Health Perspectives 2009;117(3):426-435. |
R833292 (Final) |
|
|
Yang J, Dong H, Hammock BD. Profiling the regulatory lipids: another systemic way to unveil the biological mystery. Current Opinion in Lipidology 2011;22(3):197-203. |
R833292 (2012) |
Exit |
|
Yang T, Riehl J, Esteve E, Matthaei KI, Goth S, Allen PD, Pessah IN, Lopez JR. Pharmacologic and functional characterization of malignant hyperthermia in the R163C RyR1 knock-in mouse. Anesthesiology 2006;105(6):1164-1175. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit Exit |
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Yang T, Allen PD, Pessah IN, Lopez JR. Enhanced excitation-coupled calcium entry in myotubes is associated with expression of RyR1 malignant hyperthermia mutations. Journal of Biological Chemistry 2007;282(52):37471-37478. |
R833292 (2007) R833292 (Final) R829388 (Final) |
Exit Exit Exit |
|
Zerbo O, Iosif AM, Delwiche L, Walker C, Hertz-Picciotto I. Month of conception and risk of autism. Epidemiology 2011;22(4):469-475. |
R833292 (2011) R833292 (Final) R829388 (Final) |
Exit Exit |
|
Zhang X, Lv CC, Tian J, Miao RJ, Xi W, Hertz-Picciotto I, Qi L. Prenatal and perinatal risk factors for autism in China. Journal of Autism and Developmental Disorders 2010;40(11):1311-1321. |
R833292 (2009) R833292 (Final) |
Exit Exit Exit |
|
Zivkovic AM, German JB, Esfandiari F, Halsted CH. Quantitative lipid metabolomic changes in alcoholic micropigs with fatty liver disease. Alcoholism: Clinical & Experimental Research 2009;33(4):751-758. |
R833292 (Final) |
Exit |
|
Zivkovic AM, Wiest MM, Nguyen U, Nording ML, Watkins SM, German JB. Assessing individual metabolic responsiveness to a lipid challenge using a targeted metabolomic approach. Metabolomics 2009;5(2):209-218. |
R833292 (Final) |
Exit |
|
Zivkovic AM, German JB. Metabolomics for assessment of nutritional status. Current Opinion in Clinical Nutrition and Metabolic Care 2009;12(5):501-507. |
R833292 (Final) |
Exit |
|
Zivkovic AM, Telis N, German JB, Hammock BD. Dietary omega-3 fatty acids in the modulation of inflammation and metabolic health. California Agriculture 2011;65(3):106-111. |
R833292 (Final) |
Exit Exit Exit |
|
Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proceedings of the National Academy of Sciences of the United States of America 2011;108(Suppl 1):4653-4658. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
|
Zivkovic AM, Barile D. Bovine milk as a source of functional oligosaccharides for improving human health. Advances in Nutrition 2011;2(3):284-289. |
R833292 (2012) R833292 (Final) |
Exit Exit Exit |
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Eltit JM, Li H, Ward CW, Molinski T, Pessah IN, Allen PD, Lopez JR. Orthograde dihydropyridine receptor signal regulates ryanodine receptor passive leak. Proceedings of the National Academy of Sciences of the United States of America2011;108(17):7046-7051. |
R833292 (2012) |
Exit Exit Exit |
|
Nordahl CW, Lange N, Li DD, Barnett LA, Lee A, Buonocore MH, Simon TJ, Rogers S, Ozonoff S, Amaral DG. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. Proceedings of the National Academy of Sciences of the United States of America 2011;108(50):20195-20200. |
R833292 (2012) |
Exit Exit Exit |
|
Shumway S, Thurm A, Swedo SE, Deprey L, Barnett LA, Amaral DG, Rogers SJ, Ozonoff S. Brief report: symptom onset patterns and functional outcomes in young children with autism spectrum disorders. Journal of Autism and Developmental Disorders 2011;41(12):1727-1732. |
R833292 (2012) |
Exit |
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Cunningham CL, Martinez Cerdeno V, Navarro Porras E, Prakash AN, Angelastro JM, Willemsen R, Hagerman PJ, Pessah IN, Berman RF, Noctor SC. Premutation CGG-repeat expansion of the Fmr1 gene impairs mouse neocortical development. Human Molecular Genetics 2011;20(1):64-79. |
R833292 (2012) |
Exit Exit Exit |
|
Jusko TA, De Roos AJ, Schwartz SM, Lawrence BP, Palkovicova L, Nemessanyi T, Drobna B, Fabisikova A, Kocan A, Jahnova E, Kavanagh TJ, Trnovec T, Hertz-Picciotto I. Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants. Journal of Immunotoxicology 2011;8(1):95-100. |
R833292 (2012) |
Exit |
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Ghosh R, Amirian E, Dostal M, Sram RJ, Hertz-Picciotto I. Indoor coal use and early childhood growth. Archives of Pediatrics & Adolescent Medicine 2011;165(6):492-497. |
R833292 (2012) |
Exit Exit |
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Hunsaker MR, Greco CM, Tassone F, Berman RF, Willemsen R, Hagerman RJ, Hagerman PJ. Rare intranuclear inclusions in the brains of 3 older adult males with fragile X syndrome: implications for the spectrum of fragile X-associated disorders. Journal of Neuropathology & Experimental Neurology 2011;70(6):462-469. |
R833292 (2012) |
Exit |
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Rozga A, Hutman T, Young GS, Rogers SJ, Ozonoff S, Dapretto M, Sigman M. Behavioral profiles of affected and unaffected siblings of children with autism: contribution of measures of mother-infant interaction and nonverbal communication. Journal of Autism and Developmental Disorders 2011;41(3):287-301. |
R833292 (2012) |
Exit Exit Exit |
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Bent S, Bertoglio K, Ashwood P, Bostrom A, Hendren RL. A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder. Journal of Autism Developmental Disorders 2011;41(5):545-554. |
R833292 (2012) |
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Bookman EB, McAllister K, Gillanders E, Wanke K, Balshaw D, Rutter J, Reedy J, Shaughnessy D, Agurs-Collins T, Paltoo D, Atienza A, Bierut L, Kraft P, Fallin MD, Perera F, Turkheimer E, Boardman J, Marazita ML, Rappaport SM, Boerwinkle E, Suomi SJ, Caporaso NE, Hertz-Picciotto I, Jacobson KC, Lowe WL, Goldman LR, Duggal P, Gunnar MR, Manolio TA, Green ED, Olster DH, Birnbaum LS for the NIH G × E Interplay Workshop participants. Gene-environment interplay in common complex diseases: forging an integrative model—recommendations from an NIH workshop. Genetic Epidemiology 2011;35(4):217-225. |
R833292 (2012) |
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Vivanti G, McCormick C, Young GS, Abucayan F, Hatt N, Nadig A, Ozonoff S, Rogers SJ. Intact and impaired mechanisms of action understanding in autism. Developmental Psychology 2011;47(3):841-856. |
R833292 (2012) |
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Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N. Genetic heritability and shared environmental factors among twin pairs with autism. JAMA Psychiatry (formerly Archives of General Psychiatry). 2011;68(11):1095-1102. |
R833292 (2012) |
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Young GS, Rogers SJ, Hutman T, Rozga A, Sigman M, Ozonoff S. Imitation from 12 to 24 months in autism and typical development: a longitudinal Rasch analysis. Developmental Psychology 2011;47(6):1565-1578. |
R833292 (2012) |
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Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterology Research and Practice 2011;2011:161358 (8 pp.). |
R833292 (2012) |
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Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM, Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ, Hukema RK. Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice. Acta Neuropathologica 2011;122(4):467-479. |
R833292 (2012) |
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Hunsaker MR, von Leden RE, Ta BT, Goodrich-Hunsaker NJ, Arque G, Kim K, Willemsen R, Berman RF. Motor deficits on a ladder rung task in male and female adolescent and adult CGG knock-in mice. Behavioural Brain Research 2011;222(1):117-121. |
R833292 (2012) |
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Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, Bryson S, Carver LJ, Constantino JN, Dobkins K, Hutman T, Iverson JM, Landa R, Rogers SJ, Sigman M, Stone WL. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics 2011;128(3):e488-e495. |
R833292 (2012) |
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Dutta SK, Mitra PS, Ghosh S, Zang S, Sonneborn D, Hertz-Picciotto I, Trnovec T, Palkovicova L, Sovcikova E, Ghimbovschi S, Hoffman EP. Differential gene expression and a functional analysis of PCB-exposed children: understanding disease and disorder development. Environment International 2012;40:143-154. |
R833292 (2012) |
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Jusko TA, Sonneborn D, Palkovicova L, Kocan A, Drobna B, Trnovec T, Hertz-Picciotto I. Pre- and postnatal polychlorinated biphenyl concentrations and longitudinal measures of thymus volume in infants. Environmental Health Prespectives 2012;120(4):595-600. |
R833292 (2012) |
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van Thriel C, Westerink RH, Beste C, Bale AS, Lein PJ, Leist M. Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts. Neurotoxicology 2012;33(4):911-924. |
R833292 (2012) |
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Ghosh R, Joad J, Benes I, Dostal M, Sram RJ, Hertz-Picciotto I. Ambient nitrogen oxides exposure and early childhood respiratory illnesses. Environment International 2012;39(1):96-102. |
R833292 (2012) |
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Mitra PS, Ghosh S, Zang S, Sonneborn D, Hertz-Picciotto I, Trnovec T, Palkovicova L, Sovcikova E, Ghimbovschi S, Hoffman EP, Dutta SK. Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk. Environment International 2012;39(1):188-199. |
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Barrientos GC, Feng W, Truong K, Matthaei KI, Yang T, Allen PD, Lopez JR, Pessah IN. Gene dose influences cellular and calcium channel dysregulation in heterozygous and homozygous T4826I-RYR1 malignant hyperthermia-susceptible muscle. The Journal of Biological Chemistry 2012;287(4):2863-2876. |
R833292 (2012) |
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Cao Z, Hulsizer S, Tassone F, Tang HT, Hagerman RJ, Rogawski MA, Hagerman PJ, Pessah IN. Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone. Human Molecular Genetics 2012;21(13):2923-2935. |
R833292 (2012) |
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Borthwell RM, Hunsaker MR, Willemsen R, Berman RF. Spatiotemporal processing deficits in female CGG KI mice modeling the fragile X premutation. Behavioural Brain Research 2012;233(1):29-34. |
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Bent S, Bertoglio K, Ashwood P, Nemeth E, Hendren RL. Brief report: hyperbaric oxygen therapy (HBOT) in children with autism spectrum disorder: a clinical trial. Journal of Autism Developmental Disorders 2012;42(6):1127-1132. |
R833292 (2012) |
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Lein PJ. Emerging concepts in neurotoxicology: models, mechanisms and modifying factors. NeuroToxicology 2012;33(3):516-517. |
R833292 (2012) |
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Yuen B, Boncompagni S, Feng W, Yang T, Lopez JR, Matthaei KI, Goth SR, Protasi F, Franzini-Armstrong C, Allen PD, Pessah IN. Mice expressing T4826I-RYR1 are viable but exhibit sex- and genotype-dependent susceptibility to malignant hyperthermia and muscle damage. FASEB Journal 2012;26(3):1311-1322. |
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Schebb NH, Ahn KC, Dong H, Gee SJ, Hammock BD. Whole blood is the sample matrix of choice for monitoring systemic triclocarban levels. Chemosphere 2012;87(7):825-827. |
R833292 (2012) |
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Braunschweig D, Golub MS, Koenig CM, Qi L, Pessah IN, Van de Water J, Berman RF. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. Journal of Neuroimmunology 2012;15;252(1-2):56-65. |
R833292 (2012) |
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Kaplan ES, Cao Z, Hulsizer S, Tassone F, Berman RF, Hagerman PJ, Pessah IN. Early mitochondrial abnormalities in hippocampal neurons cultured from Fmr1 pre-mutation mouse model. Journal of Neurochemistry 2012;123(4):613-621. |
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Ozonoff S. Editorial perspective: autism spectrum disorders in DSM-5--an historical perspective and the need for change. Journal of Child Psychology and Psychiatry 2012;53(10):1092-1094. |
R833292 (2012) |
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Winarni TI, Chonchaiya W, Sumekar TA, Ashwood P, Morales GM, Tassone F, Nguyen DV, Faradz SM, Van de Water J, Cook K, Hamlin A, Mu Y, Hagerman PJ, Hagerman RJ. Immune-mediated disorders among women carriers of fragile X premutation alleles. American Journal of Medical Genetics Part A 2012;158A(10):2473-2481. |
R833292 (2012) |
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Kim IH, Nishi K, Kasagami T, Morisseau C, Liu JY, Tsai HJ, Hammock BD. Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase. Bioorganic & Medicinal Chemistry Letters 2012;22(18):5889-5892. |
R833292 (2012) |
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Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, Chauhan A, Chauhan V, Dager SR, Dickson PE, Estes AM, Goldowitz D, Heck DH, Kemper TL, King BH, Martin LA, Millen KJ, Mittleman G, Mosconi MW, Persico AM, Sweeney JA, Webb SJ, Welsh JP. Consensus paper: pathological role of the cerebellum in autism. Cerebellum 2012;11(3):777-807. |
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Ozonoff S. DSM-5 and autism spectrum disorders--two decades of perspectives from the JCPP. Journal of Child Psychology and Psychiatry 2012;53(9):e4-e6 (editorial). |
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Onore C, Van de Water J, Ashwood P. Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism Research and Treatment 2012;2012:205362 (4 pp.). |
R833292 (2012) |
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Clifton MS, Wargo JP, Weathers WS, Colon M, Bennett DH, Tulve NS. Quantitative analysis of organophosphate and pyrethroid insecticides, pyrethroid transformation products, polybrominated diphenyl ethers and bisphenol A in residential surface wipe samples. Journal of Chromatography A 2013;1273:1-11. |
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Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic related air pollution, particulate matter, and autism. JAMA Psychiatry 2013;70(1):71-77. |
R833292 (2012) R835441 (2017) |
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Zerbo O, Iosif A-M, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study. Journal of Autism and Developmental Disorders 2013;43(1):25-33. |
R833292 (2012) R833292 (Final) |
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Breece E, Paciotti B, Nordahl CW, Ozonoff S, Van de Water JA, Rogers SJ, Amaral D, Ashwood P. Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors. Brain, Behavior, and Immunity 2013;31:69-75. |
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Tassone F, Choudhary NS, Tassone F, Durbin-Johnson B, Hansen R, Hertz-Picciotto I, Pessah I. Identification of expanded alleles of the FMR1 gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) study. Journal of Autism and Developmental Disorders 2013;43(3):530-539. |
R833292 (2012) |
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Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicology and Teratology 2013;36:67-81. |
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Schwartzer JJ, Koenig CM, Berman RF. Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions. Neurotoxicology and Teratology 2013;36:17-35. |
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Hertz-Picciotto I, Schmidt RJ, Walker CK, Bennett DH, Oliver M, Shedd-Wise KM, LaSalle JM, Giulivi C, Puschner B, Thomas J, Roa DL. A prospective study of environmental exposures and early biomarkers in autism spectrum disorder:design, protocols, and preliminary data from the MARBLES study. Environmental Health Perspectives 2018;126(11):117004. doi:10.1289/EHP535. |
R833292 (Final) R829388 (Final) |
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Zheng J, Yu Y, Feng W, Li J, Liu J, Zhang C, Dong Y, Pessah IN, Cao Z. Influence of nanomolar deltamethrin on the hallmarks of primary cultured cortical neuronal network and the role of ryanodine receptors. Environmental Health Perspectives 2019;127(6):67003 |
R833292 (Final) R829388 (Final) |
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Supplemental Keywords:
R83329201C001: Environmental Epidemiology: Autism, case control study, gene-environment interactions.R83329201C002: Immunological Susceptibility of Autism: Autism, immunotoxicity, autoimmunity, immunology, PCBs, PBDEs, autoantibodies.
R83329201C003: Neurodevelopmental Toxicology: mechanisms, dendritic cells, neuronal cell development, hippocampal excitability, seizures, mercury, PCBs, PBDEs.
Community Outreach and Translation Core Analytical Core: Mass spectrometry, biomarkers of autism, immunoassay, nanobody, vitamin D, glycoproteins, oligosaccharides, nutrition.
Statistical Analysis Core: Autism, biostatistics, gene selection., Scientific Discipline, Health, Genetics, Health Risk Assessment, Risk Assessments, Biochemistry, children's health, developmental neurotoxicology, ecotoxicogenomics, developmental effects, genetic analysis
Progress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R833292C001 PROJECT 1: Environmental Epidemiology of Autism
R833292C002 PROJECT 2: Immunological Susceptibility in Autism
R833292C003 PROJECT 3: Models of Neurosusceptibility
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2011 Progress Report
- 2010 Progress Report
- 2009 Progress Report
- 2008 Progress Report
- 2007 Progress Report
- Original Abstract
293 journal articles for this center