Myc is required for adaptive beta cell replication in young mice but is not sufficient in one year old mice fed with a high fat
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PROVIDER: PRJNA545355 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: To test the role of Myc in adaptive expansion of beta cells Methods: Islets were isolated from 8 week old or one year old male C57BL6 mice fed a standard or high fat diet. RNAseq and DNA mehtylseq was performed. Results: RNAseq showed that Myc target genes are upregulted in young, but not old mice after a short term high fat diet. DNA methylation analysis shows hypomethylation of cell cycle genes that are Myc targets in islets from young mice fed with a HFD. Importantly, DNA hypomethylation of Myc response elements does not occur in islets from one-year-old mice fed short-term HFD Conclusions: We conclude that Myc is required for metabolic stress-mediated beta cell expansion in young mice, but with aging Myc upregulation in beta cells is not sufficient to induce beta cell replication by, at least partly, an epigenetically-mediated resistance to Myc action.
2020-09-29 | GSE131941 | GEO
Project description: Not available
| S-EPMC6754239 | biostudies-literature
Project description:Lausannevirus one year genome evolution in allopatric versus sympatric conditions
| PRJEB20258 | ENA
Project description:We investigated ecotoxicological effects and toxicogenomic responses in fathead minnows (Pimephales promelas) exposed to an environmentally-relevant concentration (0.83 mg/L) of the munitions compound cyclotrimethylenetrinitramine (RDX) in one year and multi-generational assays. In the one year assay, RDX effects were discerned by comparing breeding groups reared in control or RDX-exposure conditions for one year. RDX had no detectable effect on gonad-somatic index, or condition factor in females assayed at 1 day and at 1, 3, 6, 9, and 12 months, however the liver-somatic index was significantly increased versus controls only at the 12 month time point. RDX had no effect on live-prey capture rates at all time points assayed and no significant impacts on egg production, fertilization or hatch success in the 1-year exposure trial. Genomic analyses indicated that RDX exposure caused limited differential expression of transcripts within time points and no functional conservation of effects indicative of RDX exposure among time points for either brain or liver tissues in the one year exposure. In the multi-generational assay, the effects of acute (96h) exposure to RDX were compared in fish reared to the F2 generation in either control or RDX-exposure conditions. The RDX-reared fish were not observed to have appreciably enhanced RDX tolerance versus the control-reared fish. However, significant differences in gene expression were observed among the control and RDX-reared fish related to neuro-excitatory glutamate metabolism, sensory signaling and processes in neurological development. In total, our results indicate that exposure to an RDX concentration approximating maximum levels observed in the field (0.83 mg/L) caused limited impacts in fathead minnows in a one year exposure, however caused altered expression in genes involved in neural function in a multi-generational exposure.
2010-07-30 | GSE21101 | GEO
Project description:We investigated ecotoxicological effects and toxicogenomic responses in fathead minnows (Pimephales promelas) exposed to an environmentally-relevant concentration (0.83 mg/L) of the munitions compound cyclotrimethylenetrinitramine (RDX) in one year and multi-generational assays. In the one year assay, RDX effects were discerned by comparing breeding groups reared in control or RDX-exposure conditions for one year. RDX had no detectable effect on gonad-somatic index, or condition factor in females assayed at 1 day and at 1, 3, 6, 9, and 12 months, however the liver-somatic index was significantly increased versus controls only at the 12 month time point. RDX had no effect on live-prey capture rates at all time points assayed and no significant impacts on egg production, fertilization or hatch success in the 1-year exposure trial. Genomic analyses indicated that RDX exposure caused limited differential expression of transcripts within time points and no functional conservation of effects indicative of RDX exposure among time points for either brain or liver tissues in the one year exposure. In the multi-generational assay, the effects of acute (96h) exposure to RDX were compared in fish reared to the F2 generation in either control or RDX-exposure conditions. The RDX-reared fish were not observed to have appreciably enhanced RDX tolerance versus the control-reared fish. However, significant differences in gene expression were observed among the control and RDX-reared fish related to neuro-excitatory glutamate metabolism, sensory signaling and processes in neurological development. In total, our results indicate that exposure to an RDX concentration approximating maximum levels observed in the field (0.83 mg/L) caused limited impacts in fathead minnows in a one year exposure, however caused altered expression in genes involved in neural function in a multi-generational exposure.
2010-07-30 | GSE21100 | GEO
Project description:We investigated ecotoxicological effects and toxicogenomic responses in fathead minnows (Pimephales promelas) exposed to an environmentally-relevant concentration (0.83 mg/L) of the munitions compound cyclotrimethylenetrinitramine (RDX) in one year and multi-generational assays. In the one year assay, RDX effects were discerned by comparing breeding groups reared in control or RDX-exposure conditions for one year. RDX had no detectable effect on gonad-somatic index, or condition factor in females assayed at 1 day and at 1, 3, 6, 9, and 12 months, however the liver-somatic index was significantly increased versus controls only at the 12 month time point. RDX had no effect on live-prey capture rates at all time points assayed and no significant impacts on egg production, fertilization or hatch success in the 1-year exposure trial. Genomic analyses indicated that RDX exposure caused limited differential expression of transcripts within time points and no functional conservation of effects indicative of RDX exposure among time points for either brain or liver tissues in the one year exposure. In the multi-generational assay, the effects of acute (96h) exposure to RDX were compared in fish reared to the F2 generation in either control or RDX-exposure conditions. The RDX-reared fish were not observed to have appreciably enhanced RDX tolerance versus the control-reared fish. However, significant differences in gene expression were observed among the control and RDX-reared fish related to neuro-excitatory glutamate metabolism, sensory signaling and processes in neurological development. In total, our results indicate that exposure to an RDX concentration approximating maximum levels observed in the field (0.83 mg/L) caused limited impacts in fathead minnows in a one year exposure, however caused altered expression in genes involved in neural function in a multi-generational exposure. Adult fathead minnows were exposed to 0.83 mg/L (0.15 mg/L standard deviation) in experimental units including 2 male and 4 fish. Five replicate males were randomly sampled with replacement from each of 8 control and 8 RDX-exposed experimental units at 1d, 1mo, 3mo, 6mo, 9mo and 12mo sampling periods. Liver tissue was investigated for differential expression in response to RDX exposure.
2010-07-30 | E-GEOD-21100 | biostudies-arrayexpress
Project description:We investigated ecotoxicological effects and toxicogenomic responses in fathead minnows (Pimephales promelas) exposed to an environmentally-relevant concentration (0.83 mg/L) of the munitions compound cyclotrimethylenetrinitramine (RDX) in one year and multi-generational assays. In the one year assay, RDX effects were discerned by comparing breeding groups reared in control or RDX-exposure conditions for one year. RDX had no detectable effect on gonad-somatic index, or condition factor in females assayed at 1 day and at 1, 3, 6, 9, and 12 months, however the liver-somatic index was significantly increased versus controls only at the 12 month time point. RDX had no effect on live-prey capture rates at all time points assayed and no significant impacts on egg production, fertilization or hatch success in the 1-year exposure trial. Genomic analyses indicated that RDX exposure caused limited differential expression of transcripts within time points and no functional conservation of effects indicative of RDX exposure among time points for either brain or liver tissues in the one year exposure. In the multi-generational assay, the effects of acute (96h) exposure to RDX were compared in fish reared to the F2 generation in either control or RDX-exposure conditions. The RDX-reared fish were not observed to have appreciably enhanced RDX tolerance versus the control-reared fish. However, significant differences in gene expression were observed among the control and RDX-reared fish related to neuro-excitatory glutamate metabolism, sensory signaling and processes in neurological development. In total, our results indicate that exposure to an RDX concentration approximating maximum levels observed in the field (0.83 mg/L) caused limited impacts in fathead minnows in a one year exposure, however caused altered expression in genes involved in neural function in a multi-generational exposure. Adult fathead minnows were exposed to 0.83 mg/L (0.15 mg/L standard deviation) in experimental units including 2 male and 4 fish. Five replicate males were randomly sampled with replacement from each of 8 control and 8 RDX-exposed experimental units at 1d, 1mo, 3mo, 6mo, 9mo and 12mo sampling periods. Brain tissue was investigated for differential expression in response to RDX exposure. Data were analyzed in 3 separate investigations. First, the Reference vs Reference data were analysed to determine an empirical false positive detection rate. Next, in order to meet milestones set up by our upper management, we were forced to generate results prior to the end of the bioassay. Therefore, we investigated gene expression among Control and RDX-exposed fish in the 1 day - 6 month sampling periods. Investigation of gene expression among the control and RDX-exposed fish for the 9 month and 12 month time periods were investigated separately.
2010-07-30 | E-GEOD-21101 | biostudies-arrayexpress
Project description:Due to difficulties inherent in designating conservation units for effective species management and conservation, the use of multiple complementary sources of information is required to identify and assess the designation of conservation units based on the degree of variation among populations within a species. In this study, we combined estimates of microsatellite and transcriptomic variation to assess the population structure and potential for adaptive variation of threatened Atlantic salmon, Salmo salar, among rivers in the Bay of Fundy. In general, population structure identified by genetic differentiation was consistent with the patterns of variation in gene expression. Both data sets provided clear indication of strong regional differentiation between rivers located within the inner Bay of Fundy relative to rivers located within the outer Bay of Fundy or the Southern Uplands region. There was also support for more refined population structure; there was some differentiation in both microsatellite and gene expression patterns between salmon from rivers in the two regions of the inner Bay of Fundy: Chignecto Bay and Minas Basin. Consistent patterns apparent in the genetic and transcriptomic dataset indicate that Atlantic salmon populations from the inner and outer Bay of Fundy reflect unique genetic lineages, with some evidence of unique genetic legacies between regions of the inner Bay of Fundy, and even between individual rivers within a region. Consistency of the microarray data across two years helps to validate the use of this technique as a useful tool in assessment of variation among wild populations for species conservation. Atlantic salmon samples used in this analysis were collected from Mactaquac and Coldbrook Biodiversity Centres on the east coast of Canada. In year one, eight individuals were hybridized per strain (five strains; 40 individuals in total). This design incorporated dye-swap replicates in which two slides were hybridized with the same pair of individuals, but the dyes were swapped for one of the slides. Therefore, in year one a total of 40 slides were used. Because of the large number of strains assessed in year two (12), dyes were balanced across slides to maximize biological replication. Six individuals were hybridized per strain; three of these were labelled with Cy3, and three were labelled with Cy5 (for a total of 36 arrays in year two).
2010-05-19 | E-GEOD-19111 | biostudies-arrayexpress
Project description:Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value=38±34%%; negative predictive value=73±30%, c-statistic=0.59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and 0.58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e. those with a relatively normal 1-year biopsy and eGFR >40) remains difficult.
2021-08-31 | GSE181757 | GEO
Project description:We previously observed reduced graft survival for kidney transplants having interstitial fibrosis with subclinical inflammation, but not fibrosis alone, on 1-year protocol biopsy. The current study aimed to determine whether fibrosis with inflammation at 1 year is associated with renal functional decline in a low-risk transplant cohort and to characterize the nature of the inflammation. Subjects were living-donor, tacrolimus/mycophenolate-treated transplant recipients without overt risk factors for reduced graft survival (n=151). Transplants with normal histology (n=86) or fibrosis alone (n=45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, while those having fibrosis with inflammation (n=20) had declining glomerular filtration rate and reduced graft survival. Immunohistochemistry confirmed increased interstitial T-cells and macrophages/dendritic cells in the fibrosis with inflammation group. Gene expression was performed on a subset of biopsies in each group and demonstrated increased expression of transcripts related to innate and cognate immunity in transplants having fibrosis with inflammation. Pathway- and pathological process-specific analyses of microarray profiles revealed that, in fibrosis with inflammation, over-expressed transcripts were enriched for potentially damaging immunological activities including Toll-like receptor signaling, antigen presentation/dendritic cell maturation, interferon gamma-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes. Thus, fibrosis with inflammation in 1-year protocol biopsies is associated with reduced graft survival and function and with a rejection-like gene expression signature even in recipients with no clinical risk for inferior outcome. Early interventions aimed at altering rejection-like inflammation may favor improved long-term KTx survival.
2010-11-01 | GSE22459 | GEO