Search results for " Sequence analysis"
showing 10 items of 294 documents
Genome interdependence in insect-bacterium symbioses
2001
Symbioses between unicellular and multicellular organisms have contributed significantly to the evolution of life on Earth. As exemplified by several studies of bacterium-insect symbioses, modern genomic techniques are providing exciting new information about the molecular basis and the biological roles of these complex relationships, revealing for instance that symbionts have lost many genes for functions that are provided by the host, but that they can provide amino acids that the host cannot synthesize.
Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells
2015
Abstract Background Apoptosis and other forms of cell death have been intensively investigated in the past years to explain the mode of action of synthetic anticancer drugs and natural products. Recently, a new form of cell death emerged, which was termed ferroptosis, because it depends on intracellular iron. Here, the role of genes involved in iron metabolism and homeostasis for the cytotoxicity of ten artemisinin derivatives have been systematically investigated. Material and methods Log10IC50 values of 10 artemisinin derivatives (artesunate, artemether, arteether, artenimol, artemisitene, arteanuin B, another monomeric artemisinin derivative and three artemisinin dimer molecules) were co…
Keratinocytes Determine Th1 Immunity during Early Experimental Leishmaniasis
2010
Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment of the early affected tissue delivers the initial triggers for Th-cell differentiation. To analyze this we studied differential gene expression in infected skin of resistant and susceptible mice 16h after parasite inoculation. Employing microarray technology, bioinformatics, laser-microdissection and in-situ-hybridization we found that the epidermis was the major source of immunomodulatory mediat…
Genome-Wide Association Analysis in Primary Sclerosing Cholangitis
2010
Background & Aims We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide association analysis of single nucleotide polymorphism (SNP) markers. Methods A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA) were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/The Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls). Results The strongest associations were detected near HLA-B at chromosome 6p21…
Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis
2013
To access publisher's full text version of this article click on the hyperlink at the bottom of the page Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci sh…
Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD.
2010
An inflammatory component is present in the microenvironment of most neoplastic tissues, including those not causally related to an obvious inflammatory process. Several microRNAs, and especially miR-155, play an essential role in both the innate and adaptative immune response. Resveratrol (trans-3,4#,5-trihydroxystilbene) is a natural antioxidant with anti-inflammatory properties that is currently at the stage of preclinical studies for human cancer prevention. Here, we establish that, in human THP-1 monocytic cells as well as in human blood monocytes, resveratrol upregulates miR- 663, a microRNA potentially targeting multiple genes implicated in the immune response. In THP-1 cells, miR-66…
Hepatocyte-Specific Smad7 Expression Attenuates TGF-β–Mediated Fibrogenesis and Protects Against Liver Damage
2008
Background & Aims The profibrogenic role of transforming growth factor (TGF)-β in liver has mostly been attributed to hepatic stellate cell activation and excess matrix synthesis. Hepatocytes are believed to contribute to increased rates of apoptosis. Methods Primary hepatocyte outgrowths and AML12 cells were used as an in vitro model to detect TGF-β effects on the cellular phenotype and expression profile. Furthermore, a transgenic mouse model was used to determine the outcome of hepatocyte-specific Smad7 expression on fibrogenesis following CCl 4 -dependent damage. Samples from patients with chronic liver diseases were assessed for (partial) epithelial-to-mesenchymal transition (EMT) in h…
Liver-specific Ldb1 deletion results in enhanced liver cancer development.
2009
Background & Aims LIM-domain-binding (Ldb) proteins have been demonstrated to be essential not only to key embryonic developmental processes but also to carcinogenesis. We have previously demonstrated Ldb1 to be of high biological and developmental relevance, as a targeted deletion of the Ldb1 gene in mice results in an embryonic lethal and pleiotropic phenotype. Methods We have now established a liver-specific Ldb1 knock out to investigate the role of Ldb1 in carcinogenesis, in particular in hepatocellular carcinoma (HCC) development, in vivo . Results These mice demonstrated a significantly enhanced growth of liver cancer by means of tumor size and number, advocating for an essential role…
Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis
2013
The mechanisms by which deregulated nuclear factor erythroid-2–related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and 13C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, reprogramming glucose metabolism. Sustained activation of NRF2 signaling in cancer cells attenuated miR-1 and miR-206 expression, leading to enhanced expression of PPP genes. Conversely, overexpression of miR-1 and miR-206 decreased the exp…
Global Functional Analyses of Cellular Responses to Pore-Forming Toxins
2011
Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we pe…