Using these samples, it has been shown that the transcriptional landscape in glomeruli of Ercc1[-/] mice at a rather young age of 14 weeks mimics that of mice which have undergone real-life renal aging. Thus, young Ercc1[-/] mice can be used as a model system for glomerular aging in future studies.
No associated publication
Age
View SamplesElevated levels of adsorbable organic bromine compounds (AOBr) have been detected in German lakes, and cyanobacteria like Microcystis, which are known for the synthesis of microcystins, are one of the main producers of natural organobromines. However, very little is known about how environmental realistic concentrations of organobromines impact invertebrates. Here, the nematode C. elegans was exposed to AOBr-containing surface water samples and to a Microcystis aeruginosa enriched batch culture (MC-BA) and compared to single organobromines and microcystin-LR exposures. Stimulatory effects were observed in certain life trait variables, which were particularly pronounced in nematodes exposed to MC-BA. A whole genome DNA-microarray revealed that MC-BA led to the differential expression of more than 2000 genes, many of which are known to be involved in metabolic, neurologic, and morphologic processes. Moreover, the up-regulation of cyp- and the down-regulation of abu-genes suggested the presence of chronic stress. However, the nematodes were not marked by negative phenotypic responses. The observed difference in MC-BA and microcystin-LR (which impacted lifespan, growth and reproduction) exposed nematodes was hypothesized to be likely due to other compounds within the batch culture. Most likely the exposure to low concentrations of organobromines appears to buffer the effects of toxic substances, like microcystin-LR.
No associated publication
No sample metadata fields
View SamplesAnimal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel antibody transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von-Willebrand-factor A like domain 2) transfer showed clear variability among inbred mouse strains; i.e. severe cutaneous blistering and inflammation in C57Bl/6J, and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57Bl/6J or MRL/MpJ mice showed an impaired ROS release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune-complex activated neutrophils from either C57Bl/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA.
Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in Experimental Epidermolysis Bullosa Acquisita.
Disease
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.
No sample metadata fields
View SamplesRibosome Profiling was employed to learn about Ribosome A-site occupancies in response to uL11 siRNA treatment or scrambled siRNA treatment in Cystic Fibrosis Bronchial Epithelial (CFBE) cells. Overall design: Ribosome Profiling of cells 96h after siRNA transfection
Slowing ribosome velocity restores folding and function of mutant CFTR.
Specimen part, Subject
View Samplessh RNA of p73 in Fibroblasts compared to non-silencing control
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
No sample metadata fields
View SamplesHead and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer.
No sample metadata fields
View SamplesWe investigated whether we could identify gene expression profiles in initial core biopsies of breast cancer samples that would permit to a) predict a clinically meaningful response to Epi/Doc in terms of tumor size reduction, b) predict a profound reduction in intratumoral Ki67 protein expression, and c) predict an in vitro response to Epi/Doc in the ATP-TCA.
No associated publication
Specimen part
View SamplesIschemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation
Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in Swine.
Specimen part
View SamplesRegulation of genes in shoots and roots and Arabidopsis in response to Zn-deficiency in wild-type and hma2 hma4 mutants plants
Systemic Upregulation of MTP2- and HMA2-Mediated Zn Partitioning to the Shoot Supplements Local Zn Deficiency Responses.
Age, Specimen part
View Samples