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GSE61233
Mus musculus
27 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
SCOPE: We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet.
Publication Title
A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Background & Aims: In this study, we investigated metabolic and molecular effects of weekly intervening 30% calorie restriction on long term natural progression of non-alcoholic fatty liver disease (NAFLD), which was induced by a medium fat diet.
Publication Title
A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
LEM Domain proteins are key components of the nuclear lamina. Mutations in LEM-D proteins cause dystrophic diseases associated with compromised adult stem cells, yet it remains unclear how LEM-D proteins support stem cell function. Studies described here use the homologue of the LEM-D protein emerin in Drosophila, Otefin (Ote) as a model to understand LEM-D protein function in adult stem cells. Loss of Ote causes female sterility due to a complex germline stem cell (GSC) phenotype that includes both an early block in germline differentiation followed by GSC death. In vivo cell cycle analysis revealed that ote mutant GSCs display a lengthened S phase.We find that loss of the DNA Damage Response (DDR) Chk2 is able to not only rescue the lengthened S phase, but also GSC death and the block in germline differentiation. Activation of detrimental checkpoint in absence of Ote is conserved in both male and female GSCs and surprisingly occurs independent of detectable canonical DDR triggers, including transposon de-repression and DNA damage. Two defects were found to occur upstream of Chk2 activation: nuclear lamina morphological defects and altered heterochromatin organization. Together, our data identify the primary cause for a compromised adult stem cell population in the absence of a LEM-D protein.
Publication Title
Nuclear lamina dysfunction triggers a germline stem cell checkpoint.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The aim of present study was to describe the genetic pathways activated during the community acquired bacterial meningitis (BM) by using genome-wide RNA expression profiling combined with functional annotation of transcriptional changes. We included 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed with GeneChip Human Gene 1.0 ST Arrays enabling the analysis of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling. Functional annotation of the enriched gene sets was used to define changed genetic networks. We also analyzed if the gene expression profile depends on the clinical course and outcome. In order to verify the genechip results, we chose ten functionally relevant genes with high statistical significance (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, IL7R) and performed quantitative real-time (qRT) PCR.We identified the significant differences at p values of <0.05 in 8569 genes and after False Discovery Rate (FDR) correction, total of 5500 genes remained significant at p value of <0.01. Quantitative RT-PCR confirmed differential expression for selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation of humoral and cellular immune responses (enrichment score 43). Those changes were found in adults and in children with BM compared to the healthy controls. Gene expression profile didnt depend on the clinical outcome, but there was very strong influence by the type of the pathogen. This study demonstrates a strong functional genomic evidence of the over-active immune response during bacterial meningitis. This hyperactive response possibly explains the complicated clinical course of this disease.
Publication Title
Peripheral blood RNA gene expression profiling in patients with bacterial meningitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways.
Publication Title
High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Calorie restriction (CR) has been shown to extend life- and health-span in model species. For most humans, a life-long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can 1) provide long-term beneficial effects and 2) counteract diet-induced obesity in male aging mice. In this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate-fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight and liver health markers in male 24-month-old mice. Hepatic gene expression profiles of INT-exposed animals appeared much more comparable to CR than to MF-exposed mice. At 12 months of age, a subgroup of MF-exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24-month-old diet switch mice were highly similar to the INT-exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life. Weekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.
Publication Title
Intermittent calorie restriction largely counteracts the adverse health effects of a moderate-fat diet in aging C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (YO>5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression.
Publication Title
Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
By regulating digestion and absorption of nutrients and providing a barrier against the external environment the intestine provides a crucial contribution to the maintenance of health. To what extent aging-related changes in the intestinal system contribute to the impaired health of the aging body is still under debate. Young (4 months) and old (21 months) male C57BL/6J mice were fed a control low-fat (10E%) or a high-fat diet (45E%) for 2 weeks. During the intervention gross energy intake and energy excretion in the feces were measured. After sacrifice the small and large intestine were isolated whereby the small intestine was divided in three equal parts. Of each of the isolated segments Swiss rolls were prepared for histological analysis and the luminal content was isolated to examine alterations in the microflora with 16S rRNA Q-PCR. Furthermore, mucosal scrapings were isolated from each segment to determine differential gene expression by microarray analysis and global DNA methylation by pyrosequencing. Digestible energy intake was similar between the two age groups on both the control and the high-fat diet implying that macronutrient metabolism is not affected in 21-month-old mice. This observation was supported by the fact that the microarray analysis on RNA from intestinal scrapings showed no marked changes in expression of genes involved in metabolic processes. Decreased expression of Cubilin was observed in the intestine of 21-month-old mice, which might contribute to aging-induced vitamin B12 deficiency. Furthermore, microarray data analysis revealed enhanced expression of a high number of genes involved in immune response and inflammation in the colon, but not in the small intestine of the 21-month-old mice. Aging-induced global hypomethylation was observed in the colon and the distal part of the small intestine, but not in the first two sections of the small intestine. In 21-month old mice the most pronounced effects of aging was observed in the colon, limited changes were observed in the small intestine.
Publication Title
Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples