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Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using(More)
terestingly, BRG1 and BRM are highly homologous 10010 North Torrey Pines Road ATPases, yet they appear to direct very different cellular La Jolla, California 92037 pathways. Gene knockout studies in mice have demonstrated that homozygous inactivating mutations in BRG1 or INI1/SNF5 (a core BAF subunit) are embryonic lethal Summary whereas BRM-inactivated(More)
Long-term EEG monitoring in chronically epileptic animals produces very large EEG data files which require efficient algorithms to differentiate interictal spikes and seizures from normal brain activity, noise, and, artifact. We compared four methods for seizure detection based on (1) EEG power as computed using amplitude squared (the power method), (2) the(More)
The development of acquired epilepsy after a perinatal hypoxic-ischemic (HI) insult was investigated in rats. After unilateral carotid ligation with hypoxia on postnatal day 7, cortical electroencephalographic and behavioral seizures were recorded with continuous radio-telemetry and video. Chronic recordings were obtained between 2 and 12 months of age in(More)
Stroke in the neonatal brain is an important cause of neurologic morbidity. To characterize the dynamics of neural progenitor cell proliferation and maturation after survival delays in the neonatal brain following ischemia, we utilized unilateral carotid ligation alone to produce infarcts in postnatal day 12 CD1 mice. We investigated the neurogenesis(More)
Neonatal stroke presents with seizures that are usually treated with phenobarbital. We hypothesized that anticonvulsants would attenuate ischemic injury, but that the dose-dependent effects of standard anticonvulsants would impact important age-dependent and injury-dependent consequences. In this study, ischemia induced by unilateral carotid ligation in(More)
Stroke in term neonates remains a significant cause of long-term neurological morbidity. This study was designed to assess the relationships between ischemic stroke induced by permanent unilateral carotid ligation in P12 CD1 mice and the structural and functional outcomes in the young mice as a consequence. After P12 ischemic strokes, mice were behaviorally(More)
Stroke is a major cause of neurologic morbidity in neonates and children. Because neonatal and pediatric stroke frequently present with seizures, the question of which anticonvulsant best blocks acute ischemic seizures and reduces injury is clinically relevant. The purpose of this study was to determine the extent to which gabapentin is neuroprotective and(More)
Hypoxic-ischemic (HI) encephalopathy is an important neurological problem of the perinatal period. Little is known of the long-term progression of HI insults or the maladaptive changes that lead to epilepsy. Using rats with unilateral carotid occlusion followed by hypoxia at postnatal day 7, this study provides an initial analysis of the epilepsy caused by(More)
New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming, and optogenetic manipulations within epileptic networks are progressively unraveling the mysteries of epileptogenesis and ictogenesis. These techniques(More)