Adam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome.
The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling.
Specimen part
View SamplesEpilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. However, the molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. The alteration in peritumoral microenvironments is believed to play a significant role in inducing epileptogenesis.
Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.
Sex, Specimen part, Disease, Disease stage
View SamplesTranscriptomes of mesenchymal stromal cells from bone marrow (bmMSC) were compared to MSC from term placenta (pMSC).
Expression of Desmoglein 2, Desmocollin 3 and Plakophilin 2 in Placenta and Bone Marrow-Derived Mesenchymal Stromal Cells.
Specimen part
View SamplesTreatment of stationary growth phase Staphylococcus aureus SA113 with 100-fold of the MIC of the lipopeptide antibiotic daptomycin leaves alive a small fraction of drug tolerant albeit genetically susceptible bacteria. This study shows that cells of this subpopulation exhibit active metabolism even hours after the onset of the drug challenge. Isotopologue profiling using fully 13C-labeled glucose revealed de novo biosynthesis of the amino acids Ala, Asp, Glu, Ser, Gly and His. The isotopologue composition in Asp and Glu suggested an increased activity of the TCA cycle under daptomycin treatment compared to unaffected stationary growth phase cells. Microarray analysis showed differential expression of specific genes 10 minutes and 3 hours after addition of the drug. Besides factors involved in drug response, a number of metabolic genes appear to shape the signature of daptomycin-tolerant S. aureus cells. These observations will be useful towards the development of new strategies against persisters and related forms of bacterial cells with downshifted physiology.
Metabolic and transcriptional activities of Staphylococcus aureus challenged with high-doses of daptomycin.
No sample metadata fields
View SamplesFor Staphylococcus aureus it was shown previously that aminocoumarinecoumarin antibiotics such as novobiocin lead to immediate down-regulation of recA expression and thereby inhibition of the SOS response, the mutation frequency and the recombination capacity. Aminocoumarinecoumarin function by inhibition of the ATPase activity of the gyrase subunit B. Here we analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. By use of a novobiocin resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and Northern blot hybridization revealed that the expression of a distinct set of genes is increased (e.g. recF-gyrB-gyrA, rib operon and ure operon )), or decreased (e.g. arlRS, recA, lukA, hlgC, fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the supercoiling level in S. aureus. Thus, down-regulation of arlRS might in part compensate for the relaxing effect of novobiocin. Novobiocin resulted in down-regulation of several of arlRS repressed target genes in an arl mutant. Global analysis and gene mapping of supercoiling sensitive genes did not give indications that they are clustered in the genome. Promoter fusion assays confirmed that responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. The results indicate that molecular property of the spacers of a given promoter dictatesa given promoter rather than chromosomal topology dictates the responsiveness towards changes in supercoiling rather than chromosomal topology.
Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus.
Treatment
View SamplesCD20 is a clinically validated target for Non-Hodgkins lymphomas and autoimmune diseases. Interactions of CD20 with the B cell receptor (BCR) and components of the BCR signaling cascade have been reported. In this study we show that antibodies against CD20 or activation of the BCR by specific antibodies induce very similar expression patterns of up- or down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa.
Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines.
Cell line, Treatment
View SamplesBackground: Several genetic defects of the nucleotide excision repair (NER) pathway, including deficiency of the Excision Repair Cross-Complementing rodent repair deficiency, complementation group 1 (ERCC1), result in pre-mature aging, impaired growth, microcephaly and delayed development of the cerebellum. Such a phenotype also occurs in ERCC1-knockout mice which survive for up to 4 weeks after birth. Therefore, we analyzed cerebellar and hippocamapal transcriptomes of these animals at 3 weeks of age to identify the candidate mechanisms underlying brain consequences of reduced ERCC1 activity.
Downregulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice.
No sample metadata fields
View SamplesBackground: Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome, DS), 18 (Edward syndrome, ES) and 13 (Patau syndrome, PS) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effects due to the trisomic chromosome, a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to define whether (1) overexpression of genes of the trisomic chromosome contributes solely to the phenotype, if (2) all genes of the trisomic chromosome are upregulated similarly and whether the ratio of gene expression is in agreement with the gene dosis, (3) whether the different trisomies behave similarly in the characteristics of transcriptional dysregulation, and (4) whether transcriptional pattern can be potentially used in prenatal diagnosis. Methods: Using oligonucleotide microarrays (Affymetrix, U133 Plus 2.0), we analyzed whole genome expression profiles representing 54.000 probe sets in cultured amniocytes (AC) and chorion villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 21, 18 and 13. Findings: We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional level of approximately 12-13 % of the supernumerary chromosome appeared similar to the respective chromosome pair in normal karyotypes. Expression values as well as the expression patterns of genes from the trisomic chromosome can distinguish the respective trisomic samples from euploid controls. A subset of chromosome 21-genes including the DSCR1-gene involved in fetal heart development was consistently up-regulated in different tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 13 and trisomy 18 vigorous downstream transcriptional changes were found. Interpretation: Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. As several transcriptional pathways are altered, complex regulatory mechanisms are involved in the pathogenesis of autosomal trisomies. A genome-wide transcriptional dysregulation was predominantly observed in trisomies 13 and 18, whereas a more to chromosome 21 restricted expression alteration was found in trisomy 21.
Specific transcriptional changes in human fetuses with autosomal trisomies.
Sex, Age, Specimen part
View SamplesThese samples were all taken from patients who underwent investigations including colonoscopy but where all tests were normal and the diagnosis of irritable bowel syndrome was reached. These observations have been used as references in studies of colonic gene expression in inflammatory bowel diseases
Clinical phenotype and gene expression profile in Crohn's disease.
No sample metadata fields
View SamplesThis is a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive component (IDC) of nine breast ductal carcinoma to identify novel molecular markers characterizing the transition from DCIS to IDC for a better understanding of its molecular biology.
Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis.
No sample metadata fields
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