Ischemic tolerance can be induced by numerous preconditioning stimuli, including various Toll-like receptor (TLR) ligands. We have shown previously that systemic administration of the TLR4 ligand, lipopolysaccharide (LPS) or the TLR9 ligand, unmethylated CpG ODNs prior to transient brain ischemia in mice confers substantial protection against ischemic damage. To elucidate the molecular mechanisms of preconditioning, we compared brain and blood genomic profiles in response to preconditioning with these TLR ligands and to preconditioning via exposure to brief ischemia.
Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury.
Specimen part, Treatment
View SamplesIn recent years, several approaches have been taken in the peptide-based immunotherapy of metastatic renal cell carcinoma (RCC), although little is known about HLA presentation on metastases compared to primary tumor and normal tissue of RCC. In this study we compared primary tumor, normal tissue and metastases with the aim of identifying similarities and differences between these tissues. We performed this comparison for two RCC patients on the level of the HLA ligandome using mass spectrometry and for three patients on the level of the transcriptome using oligonucleotide microarrays. The quantitative results show that primary tumor is more similar to metastasis than to normal tissue, both on the level of HLA ligand presentation and mRNA. We were able to characterize a total of 142 peptides in the qualitative analysis of HLA-presented peptides. Six of them were significantly overpresented on metastasis, among them a peptide derived from CD151; fourteen were overpresented on both primary tumor and metastasis compared to normal tissue, among them an HLA ligand derived from tumor protein p53. Thus, we could demonstrate that peptide-based immunotherapy might affect tumor as well as metastasis of RCC, but not healthy kidney tissue. Furthermore we were able to identify several peptides derived from tumor-associated antigens that are suitable for vaccination of metastatic RCC.
HLA ligand profiles of primary renal cell carcinoma maintained in metastases.
Sex
View SamplesThe pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we demonstrate the variation of host gene expression which underlies the contrasting hepatic pathology observed between two inbred mouse strains following schistosome infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in BALB/c and CBA mice during an active Schistosoma japonicum infection. Here, we show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. Generally, up-regulated genes were largely associated with immune and inflammatory responses, antigen processing and cytokine/chemokine activity. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with significantly greater accumulation of neutrophils at granulomatous regions, compared to CBA mice. In contrast, up-regulated expression of eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the greater degree of liver damage in these mice. Genes involved in fibrosis showed similar levels of expression in both mouse strains. Genes associated with Th1 and Th2 responses showed no significant differences in expression between strains. These results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. Furthermore, this improved understanding of schistosome immunopathogenesis in the murine model will provide the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.
Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models.
Sex, Age, Specimen part, Time
View SamplesComparison between APPPS1-FVB and APPPS1-FVBxABCC1ko mice
Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice.
Specimen part
View SamplesWe have performed bioinformatic approaches to identify the level of enrichment between gene expression profiles characterizing MSI tumors and gene changes induced in vitro by the PARP-1 inhibitor Phenanthridinone and others using the Connectivity Map tool. In a first step, we have anyzed the expression of 300 colorectal cancers from the MECC study and generated a gene expression signature by microsatellite status. The criteria followed for selection of probe sets and detailed lists to be submitted subsequently to the Connectivity Map have been published previously by us in Clinical Cancer Research in 2009. In a second step, once we observed that deficiency in MRE11 exist among MSI tumors, our interest was focused on assessing if the homologous recombination pathway showed evidence of deregulation in MSI tumors. Therefore, we examined the expression levels of those genes integrated in the KEGG pathway hsa03440 using the previously generated gene expression data set.
MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers.
Sex, Age
View SamplesWe analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells.
Immunoregulatory natural killer cells suppress autoimmunity by down-regulating antigen-specific CD8+ T cells in mice.
Specimen part, Treatment
View SamplesThe signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. The purpose of this study was to identify eye-specific genes controlled by RA during photoreceptor differentiation in the zebrafish.
Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish.
Specimen part
View SamplesChromatin packaging in sperm protects it against DNA fragmentation, and the importance of proper chromatin packaging for boar fertility outcome has become increasingly evident. Little is known however about the molecular mechanisms underlying differences in sperm DNA fragmentation and an understanding of the genes controlling this sperm parameter could help in selecting the best boars for AI use. The aim of this study was to identify differentially expressed genes in testis of Norsvin Landrace and Duroc boars with good and bad sperm DNA fragmentation using transcriptome sequencing and to use the data for polymorphism search. RNA sequence reads were obtained using Illumina technology and mapped by TopHat using the Ensembl pig database. Differentially expressed genes and pathways were analyzed using the R Bioconductor packages edgeR and goseq respectively. Using a false discovery rate of 0.05, 309 and 375 genes were found displaying significant differences in expression level between the good and bad condition in Landrace and Duroc respectively. Of the differentially expressed genes, 72 were found in common for the two breeds. Gene ontology analysis revealed that terms common for the two breeds included extracellular matrix, extracellular region and calcium ion binding. Additionally, different metabolic processes were enriched in Landrace and Duroc, whereas immune response ontologies were found to be important in Landrace. SNP detection in Landrace/Duroc identified 53182/53931 variants in 10924/10748 transcripts and of these, 1573/1827 SNPs occurred in 189/241 unique genes that were also differentially expressed. Possible high impact variants were detected using SnpEff. Transcriptome sequencing identified differentially expressed genes and nucleotide variants related to differences in sperm DNA fragmentation, and functional annotation of the genes pointed towards important biochemical pathways. This study provides insights into the genetic network underlying this trait and is a first step towards using sperm DNA fragmentation for predicting boar fertility. Overall design: Nine Landrace, five low and four high, and eleven Duroc, five low and six high, boars were selected for transcriptome profiling based on their extreme DFI values. The biological replicates within the high and low groups were compared.
RNA sequencing reveals candidate genes and polymorphisms related to sperm DNA integrity in testis tissue from boars.
Subject
View SamplesHuman primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and derive embryonic stem cell properties.
Generation of pluripotent stem cells from adult human testis.
No sample metadata fields
View SamplesThe effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling.
LXR is a negative regulator of glucose uptake in human adipocytes.
Sex, Age, Specimen part, Subject
View Samples