Prenatal environmental exposure and neurodevelopmentally important gene expression in malformed brain tissue from pediatric intractable epilepsy patients

The primary objective of this proposal was to determine whether mitochondrial oxidative stress and variation in a particular mtDNA lineage contribute to the risk of developing cortical dysplasia and are potential contributing factors in epileptogenesis in children. The occurrence of epilepsy in children is highly associated with malformations of cortical development (MCD). It appears that MCD might arise from developmental errors due to environmental exposures in combination with inherited variation in response to environmental exposures and mitochondrial function. Therefore, it is postulated that variation in a particular mtDNA lineage of children contributes to the effects of mitochondrial DNA damage on MCD phenotype. Quantitative PCR and dot blot were used to examine mitochondrial oxidative damage and single nucleotide polymorphism (SNP) in the mitochondrial genome in brain tissue from 48 pediatric intractable epilepsy patients from Miami Children’s Hospital and 11 control samples from NICHD Brain and Tissue Bank for Developmental Disorders. Epilepsy patients showed higher mtDNA copy number compared to normal health subjects (controls). Oxidative mtDNA damage was lower in non-neoplastic but higher in neoplastic epilepsy patients compared to controls. There was a trend of lower mtDNA oxidative damage in the non-neoplastic (MCD) patients compared to controls, yet, the reverse was observed in neoplastic (MCD and Non-MCD) epilepsy patients. The presence of mtDNA SNP and haplogroups did not show any statistically significant relationships with epilepsy phenotypes. However, SNPs G9804A and G9952A were found in higher frequencies in epilepsy samples. Logistic regression analysis showed no relationship between mtDNA oxidative stress, mtDNA copy number, mitochondrial haplogroups and SNP variations with epilepsy in pediatric patients. The levels of mtDNA copy number and oxidative mtDNA damage and the SNPs G9952A and T10010C predicted neoplastic epilepsy, however, this was not significant due to a small sample size of pediatric subjects. Findings of this study indicate that an increase in mtDNA content may be compensatory mechanisms for defective mitochondria in intractable epilepsy and brain tumor. Further validation of these findings related to mitochondrial genotypes and mitochondrial dysfunction in pediatric epilepsy and MCD may lay the ground for the development of new therapies and prevention strategies during embryogenesis.

Present-day Pattern Variations in the Central and Eastern Pacific El Nino

El Niño and the Southern Oscillation (ENSO) is a cycle that is initiated in the equatorial Pacific Ocean and is recognized on interannual timescales by oscillating patterns in tropical Pacific sea surface temperatures (SST) and atmospheric circulations. Using correlation and regression analysis of datasets that include SST’s and other interdependent variables including precipitation, surface winds, sea level pressure, this research seeks to quantify recent changes in ENSO behavior. Specifically, the amplitude, frequency of occurrence, and spatial characteristics (i.e. events with maximum amplitude in the Central Pacific versus the Eastern Pacific) are investigated. The research is based on the question; “Are the statistics of ENSO changing due to increasing greenhouse gas concentrations?” Our hypothesis is that the present-day changes in amplitude, frequency, and spatial characteristics of ENSO are determined by the natural variability of the ocean-atmosphere climate system, not the observed changes in the radiative forcing due to change in the concentrations of greenhouse gases. Statistical analysis, including correlation and regression analysis, is performed on observational ocean and atmospheric datasets available from the National Oceanographic and Atmospheric Administration (NOAA), National Center for Atmospheric Research (NCAR) and coupled model simulations from the Coupled Model Inter-comparison Project (phase 5, CMIP5). Datasets are analyzed with a particular focus on ENSO over the last thirty years. Understanding the observed changes in the ENSO phenomenon over recent decades has a worldwide significance. ENSO is the largest climate signal on timescales of 2 - 7 years and affects billions of people via atmospheric teleconnections that originate in the tropical Pacific. These teleconnections explain why changes in ENSO can lead to climate variations in areas including North and South America, Asia, and Australia. For the United States, El Niño events are linked to decreased number of hurricanes in the Atlantic basin, reduction in precipitation in the Pacific Northwest, and increased precipitation throughout the southern United Stated during winter months. Understanding variability in the amplitude, frequency, and spatial characteristics of ENSO is crucial for decision makers who must adapt where regional ecology and agriculture are affected by ENSO.

Present-day Pattern Variations in the Central and Eastern Pacific El Nino

El Niño and the Southern Oscillation (ENSO) is a cycle that is initiated in the equatorial Pacific Ocean and is recognized on interannual timescales by oscillating patterns in tropical Pacific sea surface temperatures (SST) and atmospheric circulations. Using correlation and regression analysis of datasets that include SST’s and other interdependent variables including precipitation, surface winds, sea level pressure, this research seeks to quantify recent changes in ENSO behavior. Specifically, the amplitude, frequency of occurrence, and spatial characteristics (i.e. events with maximum amplitude in the Central Pacific versus the Eastern Pacific) are investigated. The research is based on the question; “Are the statistics of ENSO changing due to increasing greenhouse gas concentrations?” Our hypothesis is that the present-day changes in amplitude, frequency, and spatial characteristics of ENSO are determined by the natural variability of the ocean-atmosphere climate system, not the observed changes in the radiative forcing due to change in the concentrations of greenhouse gases. Statistical analysis, including correlation and regression analysis, is performed on observational ocean and atmospheric datasets available from the National Oceanographic and Atmospheric Administration (NOAA), National Center for Atmospheric Research (NCAR) and coupled model simulations from the Coupled Model Inter-comparison Project (phase 5, CMIP5). Datasets are analyzed with a particular focus on ENSO over the last thirty years. Understanding the observed changes in the ENSO phenomenon over recent decades has a worldwide significance. ENSO is the largest climate signal on timescales of 2 - 7 years and affects billions of people via atmospheric teleconnections that originate in the tropical Pacific. These teleconnections explain why changes in ENSO can lead to climate variations in areas including North and South America, Asia, and Australia. For the United States, El Niño events are linked to decreased number of hurricanes in the Atlantic basin, reduction in precipitation in the Pacific Northwest, and increased precipitation throughout the southern United Stated during winter months. Understanding variability in the amplitude, frequency, and spatial characteristics of ENSO is crucial for decision makers who must adapt where regional ecology and agriculture are affected by ENSO.