DCs play a central role for the immune response against the mold Aspergillus fumigatus. Hypoxic microenvironments occur during infection with A. fumigatus. Hypoxia and signaling via hypoxia inducible factor 1 may modulate the response of DCs; however, the role in fungal infections is unclear.
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Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Sex, Specimen part
View SamplesDBA/2N Ahsg -/- mice suffer from sever soft tissue calcification. Gene expression in brown adipose tissue isolated from the pelvic region of 6 week old mice was analyzed, representing early stage calcification.
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Sex, Specimen part
View SamplesDBA/2N Ahsg -/- mice suffer from sever soft tissue calcification. Gene expression in whole kidney of 5-6 week old mice were analyzed, at this stage calcification is not yet macroscopically detectable.
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Sex, Specimen part
View SamplesEnteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammator microenvironment. In this study we isolated GFAP-positive myenteric glia from FVB/hGFAP-eGFP transgenic postnatal day 7 mice. Following cell sorting for the eGFP reporter, GFAP-positive EGCs were cultured for 3 weeks to generate neurosphere-like bodies. This cell culture was stimulated with LPS for 48 h and cells were employed for gene expression profiling. LPS-stimulated cell cultures were compared to untreated control cell cultures. Enriched GFAP+ EGC cultures secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Further, in vitro cultures were compared to GFAP-eGFP-positive cells directly analyzed after cell sorting of small intestinal LMMP digests (in vivo) to assess alterations in transcriptomic profiles due to the in vitro culture.
Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo.
Specimen part
View SamplesThe p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity. While p53 and the p73 isoform p73gamma have basic CTDs and form weak sequence-specific protein-DNA complexes, the major p73 isoforms alpha, beta and delta have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein-DNA complex stability, intranuclear mobility, promoter occupancy in vivo, transgene activation and induction of cell cycle arrest or apoptosis. A basic CTD in p53 and p73gamma therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. In contrast, most p73 isoforms exhibit constitutive DNA binding activity consistent with a predominant role in developmental control.
C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity.
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View Samplessh RNA of p73 in Fibroblasts compared to non-silencing control
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
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View SamplesTriggering of B cell receptors (BCR) induces a massive synthesis of NFATc1 in splenic B cells. By inactivating the Nfatc1 gene and re-expressing NFATc1 we show that NFATc1 levels are critical for the survival of splenic B cells upon BCR stimulation. NFATc1 ablation led to decreased BCR-induced Ca++ flux and proliferation of splenic B cells, increased apoptosis and suppressed germinal centre formation and immunoglobulin class switch by T cell-independent antigens. By controlling IL-10 synthesis in B cells, NFATc1 supported the proliferation and IL-2 synthesis of T cells in vitro and appeared to contribute to the mild clinical course of Experimental Autoimmune Encephalomyelitis in mice bearing NFATc1-/- B cells. These data indicate NFATc1 as a key factor controlling B cell function.
NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
Specimen part
View SamplesIn this study we analyzed the myeloma cell contact-mediated changes on the transcriptome of skeletal precursor cells. Therefore, human mesenchymal stem cells (MSC) and osteogenic precursor cells (OPC) were co-cultured with the representative myeloma cell line INA-6 for 24 h. Afterwards, MSC and OPC were separated from INA-6 cells by fluorescence activated cell sorting. Total RNA of MSC and OPC fractions was used for whole genome array analysis.
Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells -Implications for myeloma bone disease.
Sex, Age, Specimen part, Disease stage
View SamplesRationale: Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate receptors ER and ER. Since female sex hormones enhance global glucose utilization and because myocardial function and mass are tightly linked to cardiac glucose metabolism we tested the hypothesis that expression and activation of the estrogen receptor (ER) might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Methods and Results: Cardiac glucose uptake quantified in vivo by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was strongly impaired in ovarectomized compared to gonadal intact female C57BL/6JO mice. The selective ER agonist 16-LE2 and the non-selective ER and ER agonist 17-estradiol completely restored cardiac glucose uptake in ovarectomized mice. Cardiac FDG uptake was strongly decreased in female ER knockout mice (ERKO) compared to wild type littermates. Biochemical assays, affymetrix cDNA array analysis, western blotting and immuno-staining of cardiac glucose transporters revealed a positive correlation of ER dependent cardiac FDG uptake with preserved cardiac glucose transporter-1 expression and micro-vascular localization. Conclusions: Systemic activation of the ER estrogen receptor is sufficient and its expression is required to maintain physiological glucose uptake in the murine heart, which is likely to contribute to known cardio-protective estrogen effects.
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Sex, Age, Specimen part
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