Ontology highlight
ABSTRACT:
PROVIDER: PRJNA857184 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20067762_1.fastq.gz | Fastqsanger.gz | |||
| SRR20067762_2.fastq.gz | Fastqsanger.gz | |||
| SRR20067763_1.fastq.gz | Fastqsanger.gz | |||
| SRR20067763_2.fastq.gz | Fastqsanger.gz | |||
| SRR20067764_1.fastq.gz | Fastqsanger.gz |
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Project description:This study investigates stress's impact on Alzheimer's disease (AD) using male APP/PS1 transgenic mice. Negative stressors (chronic social defeat, restraint) and positive hedonia (environmental enrichment, EE) were applied. Stress worsens AD pathology, while EE slows progression. Brain RNA-seq reveals IL-6 and IL-10 as key stress-related AD regulators. Flow cytometry shows CD8+/CD4+ T cell ratio shifts in response to SE and EE. SE increases CD8+/CD4+ ratio, opposite in EE. Depletion and enrichment of CD8+ T cells both accelerate AD, indicating immune intervention's negative impact. Stress management and balanced immunity may aid AD therapy, highlighting novel potential treatment.
2023-12-15 | GSE244131 | GEO
Project description:Epidemiological studies have shown that lower activity of the cholesteryl ester transfer protein (CETP) correlates with reduced Alzheimer’s disease (AD) risk. While small molecule CETP inhibitors like evacetrapib have previously been assessed for cardiovascular diseases, their involvement in AD has not been investigated. Here, we establish CETP as a novel pharmacological target for AD treatment. Using CETP transgenic mice crossed to a mouse model of amyloidosis and administering evacetrapib, we provide evidence that CETP inhibition maintained memory independent of classic AD markers, increased hippocampal cholesterol, altered plasma lipoproteins, and changed transcription of genes linked to brain barriers. Using proteomic data of cerebrospinal fluid (CSF) from cognitively unimpaired at-risk individuals at risk for AD in the PResymptomatic EValuation of Experimental or Novel Treatments for AD (PREVENT-AD) cohort, we confirm that our mouse model reflects physiological changes in pre-symptomatic human subjects. We propose the repurposing of CETP inhibitors as an effective therapeutic strategy to delay or prevent cognitive impairment in AD.
2026-04-10 | GSE314221 | GEO
Project description:Estrogens impair bile acid (BA) homeostasis, leading to intrahepatic cholestasis of pregnancy (ICP). ICP is characterized by elevated serum bilirubin and BAs, severe pruritus, and an increased risk of adverse perinatal outcomes. The constitutive androstane receptor (CAR) regulates genes involved in xenobiotic and BA detoxification. Previous studies suggest that CAR activation is protective in bile duct ligation–induced cholestasis and that major genes involved in BA elimination are downregulated in ethinylestradiol (EE)–induced cholestasis in mice. We examined whether CAR ligands could ameliorate cholestasis and prevent hepatic injury in an EE-induced cholestasis model using biochemical, transcriptomic, and BA metabolomic analyses. We found that estradiol inhibits and downregulates CAR target genes in vitro. Consistently, EE significantly suppresses hepatic CAR target gene expression in vivo, whereas the murine CAR agonist TCPOBOP partially restores the expression of selected detoxification genes, improves plasma alkaline phosphatase levels, and decreases hepatic BA accumulation. In humanized PXR–CAR–CYP3A mice with EE-induced cholestasis, MI763F, a novel and potent human CAR agonist, recapitulates the effects of TCPOBOP on key genes involved in BA metabolism and the BA metabolome, and significantly reduces hepatic BA accumulation. These results demonstrate that CAR ligands counteract EE-mediated disruption of genes involved in BA homeostasis.
2026-06-01 | GSE314547 | GEO
Project description:Bifidobacterium breve represents one of the most abundant (bifido)bacterial species in the gastro-intestinal tract of (breast-fed) infants, where their presence is believed to be beneficial. In the present study whole genome sequencing, employing PacBio’s Single Molecule, Real-Time (SMRT) sequencing platform, combined with comparative genome analysis allowed the most extensive genetic investigation of this taxon. Our findings demonstrate that Restriction/Modification (R/M) systems constitute a substantial part of the B. breve variome. Availing of the methylome data generated by SMRT sequencing, combined with targeted Illumina bisulfite sequencing (BiSeq) and comparative genome analysis, we were able to detect methylation recognition motifs and assign these to identified B. breve R/M systems, where in several cases such assignments were confirmed by restriction analysis. Furthermore, cloning of a selected methyltransferase-encoding gene validated the activity of the corresponding R/M system, and was shown to overcome the barrier they impose to genetic accessibility, thus allowing future genetic manipulation of members of this species.
2017-12-13 | GSE104927 | GEO
Project description:Using a mouse model overexpressing human SNCA and profiling the hippocampal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through long-term enriched environment (EE) exposure. We observed that EE prevented perturbations of genes attributed to neuronal and glial cell types and linked to glutamate signaling, calcium homeostasis, inflammation, and related processes of SNCA biology. Cluster and promoter analyses suggested driver genes that specifically responded to the EE, and pointed to a pivotal role of Egr1 to have hierarchically activated other drivers. We suggest a model in which EE-induced driver genes prevent and counter-balance perturbations of SNCA overexpression, restoring a largely normalized gene expression profile and system state.
2018-05-14 | GSE96961 | GEO
Project description:Phenotypic screening of a random mutant library combined with microarray analysis of the transcriptional response of B. breve UCC2003 to iron limitation, allowed the identification of a number of genes implicated in the survival of Bifidbacterium breve UCC2003 under iron-limiting conditions. Of the identified genes, two putative iron-uptake systems, were further characterised: (i) a presumed ferrous iron uptake system, designated here as bfeUO, and (ii) a predicted ferric iron/siderophore uptake system, designated sifABCDE. In silico analysis also illustrated that these two clusters are highly conserved across members of the genus Bifidobacterium and are invariably co-located. Murine colonization studies demonstrated that B. breve UCC2003-bfeU and B. breve UCC2003-sifA insertion mutants are able to colonize a healthy murine gut as efficiently as the wild type B. breve strain, indicating that these genes are not crucial for gut survival or colonization in a healthy host.
2016-12-23 | GSE92758 | GEO
Project description:Alzheimer’s disease (AD) is a serious neurodegenerative disease in which miRNAs have been linked to its pathogenesis. miR-603 is a primate-specific miRNA. Through ADNI data analysis, we found a SNP rs11014002 in pre-miR-603 which promotes the biogenesis of mature miR-603 is associated with AD risk. We further identified that LRPAP1, a protein which antagonizes the function of LRP1 in Aβ clearance and AD susceptibility, is a target gene of miR-603. Moreover, overexpression of miR-603 increased the protein level of LRP1, suggesting the protective role of miR-603 in AD. Both significant increase and loss of regulatory function of miR-603 hint the existence of a compensatory mechanism in hippocampus of AD subjects. Furthermore, we found that miR-603 could directly downregulate E2F1 and prevent cells from H2O2 induced-apoptosis. This work provides the first evidence that miR-603 may modulate AD susceptibility and the SNP rs11014002 (T-carrier genotype) might be a protective factor for AD. There are two groups: Negative Control and miR-603 overexpression. We performed experiments on HEK293 cell and Hela cell.
2015-05-18 | E-GEOD-68987 | biostudies-arrayexpress
Project description:Environmental enrichment (EE) conditions have profound beneficial effects for reinstating cognitive ability in neuropathological disorders like Alzheimer’s disease (AD). While EE benefits involve epigenetic gene control mechanisms that comprise histone acetylation, the histone acetyltransferases (HATs) involved remain largely unknown. Here, we examine a role for Tip60 HAT action in mediating activity- dependent beneficial neuroadaptations to EE using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that flies raised under EE conditions display enhanced MB axonal outgrowth, synapse protein production, histone acetylation induction and transcriptional activation of cognition linked genes when compared to their genotypically identical siblings raised under isolated conditions. Further, these beneficial changes are impaired in both Tip60 HAT mutant flies and APP neurodegenerative flies. While EE conditions provide only slight beneficial neuroadaptive changes in the APP neurodegenerative fly MB, such positive changes are significantly enhanced by increasing MB Tip60 HAT levels. Our results implicate Tip60 as a critical mediator of EE-induced benefits, and provide insight into synergistic behavioral and epigenetic based approaches for treatment of cognitive disorders. EE has been shown to positively impact gene expression profiles in the mouse brain that are enriched in functions such as neuronal structure, synaptic plasticity and neurotransmission. Thus, we asked whether the EE induced beneficial MB structural and synaptic changes we observe are accompanied by neuroadaptive transcriptional benefits in the Drosophila MB, and if so, is Tip60 HAT action required for this process. To address this question, we accessed EE induced beneficial transcriptional changes using microarray.
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Project description:Enteroendocrine cells (EEs) in the intestinal epithelium have important endocrine functions, yet this cell lineage exhibits great local and regional variations that have hampered detailed characterization of EE subtypes. Through single cell RNA-sequencing analysis, combined with a collection of neuropeptide/receptor knock-in strains, here we provide a comprehensive analysis of cellular diversity, spatial distribution and transcription factor (TF) code of EEs in adult Drosophila midgut. We identify 10 major EE subtypes that totally produced 14 different classes of hormone peptides. Each EE on average co-produces 2-5 different classes of hormone peptides. Functional screen with subtype-enriched TFs suggests a combinatorial TF code that controls EE cell diversity, with class-specific TFs Mirr and Ptx1that respectively define two major classes of EEs, and regional TFs such as Esg, Drm, Exex and Fer1that further define regional EE identity. Our single-cell data should greatly facilitate Drosophila modeling of EE differentiation and function.
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Project description:This work reports on the identification and molecular characterization of a two-component regulatory system (2CRS), encoded by phoRP in Bifidobacterium breve UCC2003, which controls the response to phosphate (Pi) starvation. The response regulator PhoP was shown to bind to the promoter region of pstSCAB, specifying a predicted Pi transporter system, as well as that of phoU, which specifies a putative Pi-responsive regulatory protein. This interaction is assumed to cause transcriptional activation under conditions of Pi limitation. The phoRP genes appear to be subject to positive auto-regulation, and with pstSCAB and phoU, represent the complete regulon controlled by the phoRP-encoded 2CRS in B. breve UCC2003. Determination of the minimal PhoP binding region combined with bioinformatic analysis revealed the probable recognition sequence of PhoP, designated here as the PHO box, which together with phoRP is conserved among many high GC-content Gram+ bacteria. The importance of the phoRP 2CRS in the response of B. breve to Pi starvation conditions was confirmed by generating a B. breve::phoP insertion mutant which exhibited decreased growth under phosphate-limiting conditions as compared to its parent strain UCC2003. In order to investigate differences in global gene expression upon growth of B. breve UCC2003 under low phosphate conditions compared to normal growing cells, DNA microarray experiments were performed in CDM. Total RNA was isolated from B. breve UCC2003 cultures under normal conditions and cultures grown under low phosphate conditions. Starvation experiments with wildtype and overexpression strains were performed in triplicate, while knockout array experiments where performed as single experiments and targets were confirmed with QRT-PCR.
2012-09-06 | E-GEOD-34983 | biostudies-arrayexpress