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Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate immune responses and prevent excessive inflammation. The nervous(More)
In response to bacterial endotoxin (e.g., LPS) or endogenous proinflammatory cytokines (e.g., TNF and IL-1beta), innate immune cells release HMGB1, a late cytokine mediator of lethal endotoxemia and sepsis. The delayed kinetics of HMGB1 release makes it an attractive therapeutic target with a wider window of opportunity for the treatment of lethal systemic(More)
Localized accessibility of critical DNA sequences to the regulatory machinery is a key requirement for regulation of human genes. Here we describe a high-resolution, genome-scale approach for quantifying chromatin accessibility by measuring DNase I sensitivity as a continuous function of genome position using tiling DNA microarrays (DNase-array). We(More)
Distinct subtypes of cortical GABAergic interneurons provide inhibitory signals that are indispensable for neural network function. The Dlx homeobox genes have a central role in regulating their development and function. We have characterized the activity of three cis-regulatory sequences involved in forebrain expression of vertebrate Dlx genes: upstream(More)
Motivation: In the living cell nucleus, genomic DNA is packaged into chromatin. DNA sequences that regulate transcription and other chromosomal processes are associated with local disruptions, or ‘openings’, in chromatin structure caused by the cooperative action of regulatory proteins. Such perturbations are extremely specific for cis-regulatory elements(More)
Somatic mutations and large-scale depletion in mitochondrial DNA (mtDNA) have been extensively detected in various human cancers. However, it still remains unclear whether the alterations in mtDNA content are related to the clinicopathological parameters and patient prognosis in breast cancer. In the present study, we analyzed the copy number of mtDNA in 59(More)
Mitochondria are key organelles in eukaryotic cells principally responsible for multiple cellular functions. In addition to a plethora of somatic mutations as well as polymorphic sequence variations in mitochondrial DNA (mtDNA), the identification of increased or reduced mtDNA copy number has been increasingly reported in a broad range of primary human(More)
We developed a quantitative methodology, digital analysis of chromatin structure (DACS), for high-throughput, automated mapping of DNase I-hypersensitive sites and associated cis-regulatory sequences in the human and other complex genomes. We used 19/20-bp genomic DNA tags to localize individual DNase I cutting events in nuclear chromatin and produced(More)
Dlx homeobox genes play a crucial role in the migration and differentiation of the subpallial precursor cells that give rise to various subtypes of gamma-aminobutyric acid (GABA)-expressing neurons of the forebrain, including local-circuit cortical interneurons. Aberrant development of GABAergic interneurons has been linked to several neurodevelopmental(More)
PURPOSE We examined changes of the central nervous system in patients with advanced primary open-angle glaucoma (POAG). METHODS The clinical observational study included 15 patients with bilateral advanced POAG and 15 healthy normal control subjects, matched for age and sex with the study group. Retinal nerve fiber layer (RNFL) thickness was measured by(More)