Female infertility syndromes are among the most prevalent chronic health disorders in women, but their molecular basis remains unknown because of the complexity of oogenesis and uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover such ovarian fertility factors en masse, we employed a mouse model (Foxo3), where follicles are assembled normally but are then synchronously activated. Gene expression profiling of mutant and normal ovaries led to the identification a surprisingly large set of ovarian factors. The set included the vast majority of known ovarian factors, many of which when mutated produce female sterility phenotypes, but most were novel. Subsequent analyses revealed novel classes of ovarian factors and significant overrpresentation on the X chromosome, among other insights into the general properties of oogenesis genes and their patterns of expression.
Genomewide discovery and classification of candidate ovarian fertility genes in the mouse.
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View SamplesLysR-type transcriptional regulators (LTTRs) are emerging as key circuit components in regulating microbial stress responses and are implicated in modulating oxidative stress in the human opportunistic pathogen Pseudomonas aeruginosa. The oxidative stress response encapsulates several strategies to overcome the deleterious effects of reactive oxygen species. However, many of the regulatory components and associated molecular mechanisms underpinning this key adaptive response remain to be characterised. Comparative analysis of publically available transcriptomic datasets led to the identification of a novel LTTR, PA2206, whose expression was altered in response to a range of host signals in addition to oxidative stress. PA2206 was found to be required for tolerance to H2O2 in vitro and lethality in vivo in the Zebrafish embryo model of infection. Transcriptomic analysis in the presence of H2O2 showed that PA2206 altered the expression of 58 genes, including a large repertoire of oxidative stress and iron responsive genes, independent of the master regulator of oxidative stress, OxyR. Contrary to the classic mechanism of LysR regulation, PA2206 did not autoregulate its own expression and did not influence expression of adjacent or divergently transcribed genes. The PA2214-15 operon was identified as a direct target of PA2206 with truncated promoter fragments revealing binding to the 5-ATTGCCTGGGGTTAT-3 LysR box adjacent to the predicted -35 region. PA2206 also interacted with the pvdS promoter suggesting a global dimension to the PA2206 regulon, and suggests PA2206 is an important regulatory component of P. aeruginosa adaptation during oxidative stress.
A non-classical LysR-type transcriptional regulator PA2206 is required for an effective oxidative stress response in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesWe recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations prior to wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Overall design: Lewis Lung Carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2, 3, or 4 wks and compared to PBS injected control. Muscle wasting was evident at 4 wks LLC. Animals were anesthetized using isoflourane and gastrocnemius muscles were collected for analysis. Conclusions: Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.
Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice.
Specimen part, Cell line, Subject
View SamplesATFS-1 has been shown to regulate transcription of mitochondrial chaperone genes such as mtHsp70/hsp-6 and hsp-60 in response to mitocondrial stress. To identify the entire ATFS-1-mediated response, we compared the transcript profiles from wild-type and atfs-1(tm4525) worms raised in the absence and presence of mitochondrial stress.
Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.
Specimen part
View SamplesWe previously identified a number of genes which were differentially expressed during mitochondrial stress in an ATFS-1-dependent manner using an atfs-1 loss-of-function mutant allele . To complement the findings from our previous microarray, we compared the transcript profiles from wild-type and atfs-1(et18) gain-of-function worms (which have constitutively active ATFS-1) in the absence of mitochondrial stress.
Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response.
Specimen part
View SamplesZIP-3 has been shown to repress the mitochondrial-UPR response. To identify genes repressed by ZIP-3, we compared transcript profiles from wildtype, atfs-1(tm4919) and zip-3(gk3164) worms raised on control RNAi or spg-7 RNAi Overall design: RNA samples were prepared from wild-type(wt) and zip-3(gk3164)(mutant) worms fed either control RNAi or spg-7 RNAi. Worms were synchronized by bleaching, raised on NGM plates seeded with control RNAi or spg-7 RNAi till L4 stage and then harvested. Each experiment was performed in triplicate indicated as 1,2 and 3.
Mitochondrial UPR repression during <i>Pseudomonas aeruginosa</i> infection requires the bZIP protein ZIP-3.
Specimen part, Subject
View SamplesZIP-3 has been shown to repress the mitochondrial-UPR genes and immune response during P. aeruginosa infection. To identify genes repressed by ZIP-3, we compared transcript profiles from wildtype and zip-3(gk3164) worms raised on P. aeruginosa or E. coli. Overall design: RNA samples were prepared from wild-type(wt) and zip-3(gk3164)(mutant) worms fed either E. coli or P. aeruginosa. Worms were synchronized by bleaching, starved on empty NGM plates for 48h, transferred to E. coli or P. aeruginosa seeded NGM plates for 18h and then harvested. Each experiment was performed in triplicate indicated as 1,2 and 3.
Mitochondrial UPR repression during <i>Pseudomonas aeruginosa</i> infection requires the bZIP protein ZIP-3.
Specimen part, Subject
View SamplesTo determine the effect on gene expression of intratumoral injection of the Toll-like receptor agonist CpG1826. MC38 colon cancer cells were injected subcutaneously into C57BL/6 mice and allowed to establish until ~40 mm2.
Toll-Like Receptor Triggering and T-Cell Costimulation Induce Potent Antitumor Immunity in Mice.
Specimen part
View SamplesBackground
Expression quantitative trait loci mapping identifies new genetic models of glutathione S-transferase variation.
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View SamplesReceptor tyrosine kinases MET and EGFR are critically involved in initiation of liver regeneration. Other cytokines and signaling molecules also help in the early part of the process. Regeneration employs effective redundancy schemes to compensate for missing signals. Elimination of any single signaling pathway only delays but does not abolish the process. Our present study, however, shows that combined systemic elimination of MET and EGFR signaling abolishes liver regeneration, prevents restoration of liver mass and leads to liver decompensation. Our results demonstrate that liver function is dependent on synchronous availability of signaling from these two pathways. The study shows that MET and EGFR separately control many non-overlapping signaling endpoints, allowing for compensation when only one of the signals is blocked. The combined elimination of the signals however was not tolerated. The results provide critical new information on interactive MET and EGFR signaling and the contribution of their combined absence to regeneration arrest and liver decompensation.
Combined systemic elimination of MET and epidermal growth factor receptor signaling completely abolishes liver regeneration and leads to liver decompensation.
Specimen part, Time
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