Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barretts Metaplasia, with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-kB, driving the aberrant expression of intestine-specific caudal-related homeobox genes. However, early events in the pathogenesis of Barretts Metaplasia from a normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression. Initial 2D experiments with a range of bile salts observed that taurochenodeoxycholate (TCDC) impacted upon NF-kB activation without causing cell death. Informed by this, the 3D human oesophageal model was repeatedly exposed to TCDC in the presence and absence of acid, and the epithelial cells underwent gene expression profiling. We identified ~300 differentially expressed genes following each treatment, with a large and significant overlap between treatments. Enrichment analysis (Broad GSEA, DAVID and Metacore, GeneGo Inc) identified multiple gene sets related to cell signalling, inflammation, proliferation, differentiation and cell adhesion. Specifically NF-kB activation, Wnt signalling, cell adhesion and targets for the transcription factors PTF1A and HNF4 were highlighted. CDX1/2 transcription factors are believed to play a role in BM development; however, in this study their targets were not enriched, suggesting that CDX1/2 activation may not be the one of the initial events for BM formation. Our findings highlight new areas for investigation in the earliest stages of BM pathogenesis of oesophageal diseases and new potential therapeutic targets.
Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.
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C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis.
Specimen part, Subject
View SamplesObjective: An intronic GGGGCC-repeat expansion of C9ORF72 is the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The mechanism of neurodegeneration is unknown, but a direct effect on RNA processing mediated by RNA foci transcribed from the repeat sequence has been proposed.
C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones.
Specimen part, Cell line, Treatment
View SamplesAims: Loss of nuclear TDP-43 characterises sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP-43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether 1) RNA splicing dysregulation is present in lower motor neurons in ALS and in a motor neuron-like cell model, and 2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient-derived fibroblasts.
Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones.
Specimen part
View SamplesAims: Loss of nuclear TDP-43 characterises sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP-43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether 1) RNA splicing dysregulation is present in lower motor neurons in ALS and in a motor neuron-like cell model, and 2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient-derived fibroblasts.
Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones.
Specimen part
View SamplesManuka honey has been shown to inhibit growth in EMRSA-15 by inhibiting cell division, the mode of actin is currently unclear.
Synergy between oxacillin and manuka honey sensitizes methicillin-resistant Staphylococcus aureus to oxacillin.
No sample metadata fields
View SamplesObjective: to identify the early molecular processes involved in osseointegration associated with a micro roughened and nanosurface featured implants.
Comparative molecular assessment of early osseointegration in implant-adherent cells.
Sex, Specimen part
View SamplesNeuronal differentiation of PC12 cells in response to NGF is a prototypical model in which signal duration determines a biological response. Sustained ERK activity induced by NGF, as compared to transient activity induced by EGF, is critical to the differentiation of these cells. To characterize the transcriptional program activated preferentially by NGF, we compared global gene expression profiles between cells treated with NGF and EGF for 2-4 hrs, when sustained ERK signaling in response to NGF is most distinct from the transient signal elicited by EGF. This analysis identified 69 genes that were preferentially upregulated in response to NGF.
Global expression analysis identified a preferentially nerve growth factor-induced transcriptional program regulated by sustained mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and AP-1 protein activation during PC12 cell differentiation.
Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
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