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Search Results: 1 - 10 of 27432 matches for " Geffers Robert "
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Differential Gene Expression from Genome-Wide Microarray Analyses Distinguishes Lohmann Selected Leghorn and Lohmann Brown Layers
Christin Habig, Robert Geffers, Ottmar Distl
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046787
Abstract: The Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) layer lines have been selected for high egg production since more than 50 years and belong to the worldwide leading commercial layer lines. The objectives of the present study were to characterize the molecular processes that are different among these two layer lines using whole genome RNA expression profiles. The hens were kept in the newly developed small group housing system Eurovent German with two different group sizes. Differential expression was observed for 6,276 microarray probes (FDR adjusted P-value <0.05) among the two layer lines LSL and LB. A 2-fold or greater change in gene expression was identified on 151 probe sets. In LSL, 72 of the 151 probe sets were up- and 79 of them were down-regulated. Gene ontology (GO) enrichment analysis accounting for biological processes evinced 18 GO-terms for the 72 probe sets with higher expression in LSL, especially those taking part in immune system processes and membrane organization. A total of 32 enriched GO-terms were determined among the 79 down-regulated probe sets of LSL. Particularly, these terms included phosphorus metabolic processes and signaling pathways. In conclusion, the phenotypic differences among the two layer lines LSL and LB are clearly reflected in their gene expression profiles of the cerebrum. These novel findings provide clues for genes involved in economically important line characteristics of commercial laying hens.
A Replication Study for Genome-Wide Gene Expression Levels in Two Layer Lines Elucidates Differentially Expressed Genes of Pathways Involved in Bone Remodeling and Immune Responsiveness
Christin Habig, Robert Geffers, Ottmar Distl
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098350
Abstract: The current replication study confirmed significant differences in gene expression profiles of the cerebrum among the two commercial layer lines Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB). Microarray analyses were performed for 30 LSL and another 30 LB laying hens kept in the small group housing system Eurovent German. A total of 14,103 microarray probe sets using customized Affymetrix ChiGene-1_0-st Arrays with 20,399 probe sets were differentially expressed among the two layer lines LSL and LB (FDR adjusted P-value <0.05). An at least 2-fold change in expression levels could be observed for 388 of these probe sets. In LSL, 214 of the 388 probe sets were down- and 174 were up-regulated and vice versa for the LB layer line. Among the 174 up-regulated probe sets in LSL, we identified 51 significantly enriched Gene ontology (GO) terms of the biological process category. A total of 63 enriched GO-terms could be identified for the 214 down-regulated probe sets of the layer line LSL. We identified nine genes significantly differentially expressed between the two layer lines in both microarray experiments. These genes play a crucial role in protection of neuronal cells from oxidative stress, bone mineral density and immune response among the two layer lines LSL and LB. Thus, the different regulation of these genes may significantly contribute to phenotypic trait differences among these layer lines. In conclusion, these novel findings provide a basis for further research to improve animal welfare in laying hens and these layer lines may be of general interest as an animal model.
Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions
Seifert Oliver,Matussek Andreas,Sj?gren Florence,Geffers Robert
Journal of Inflammation , 2012, DOI: 10.1186/1476-9255-9-43
Abstract: Background Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-α inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. Methods Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. Results Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. Conclusion The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions.
Global Transcriptome Analysis in Influenza-Infected Mouse Lungs Reveals the Kinetics of Innate and Adaptive Host Immune Responses
Claudia Pommerenke, Esther Wilk, Barkha Srivastava, Annika Schulze, Natalia Novoselova, Robert Geffers, Klaus Schughart
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041169
Abstract: An infection represents a highly dynamic process involving complex biological responses of the host at many levels. To describe such processes at a global level, we recorded gene expression changes in mouse lungs after a non-lethal infection with influenza A virus over a period of 60 days. Global analysis of the large data set identified distinct phases of the host response. The increase in interferon genes and up-regulation of a defined NK-specific gene set revealed the initiation of the early innate immune response phase. Subsequently, infiltration and activation of T and B cells could be observed by an augmentation of T and B cell specific signature gene expression. The changes in B cell gene expression and preceding chemokine subsets were associated with the formation of bronchus-associated lymphoid tissue. In addition, we compared the gene expression profiles from wild type mice with Rag2 mutant mice. This analysis readily demonstrated that the deficiency in the T and B cell responses in Rag2 mutants could be detected by changes in the global gene expression patterns of the whole lung. In conclusion, our comprehensive gene expression study describes for the first time the entire host response and its kinetics to an acute influenza A infection at the transcriptome level.
Local Induction of Immunosuppressive CD8+ T Cells in the Gut-Associated Lymphoid Tissues
Diana Fleissner,Wiebke Hansen,Robert Geffers,Jan Buer,Astrid M. Westendorf
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015373
Abstract: In contrast to intestinal CD4+ regulatory T cells (Tregs), the generation and function of immunomodulatory intestinal CD8+ T cells is less well defined. To dissect the immunologic mechanisms of CD8+ T cell function in the mucosa, reactivity against hemagglutinin (HA) expressed in intestinal epithelial cells of mice bearing a MHC class-I-restricted T-cell-receptor specific for HA was studied.
Evaluation of a microarray-hybridization based method applicable for discovery of single nucleotide polymorphisms (SNPs) in the Pseudomonas aeruginosa genome
Andreas D?tsch, Claudia Pommerenke, Florian Bredenbruch, Robert Geffers, Susanne H?ussler
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-29
Abstract: We developed a microarray-based method applicable for discovery of single nucleotide polymorphisms (SNPs) in P. aeruginosa as an easy and economical alternative to whole genome sequencing. About 50% of all SNPs theoretically covered by the array could be detected in a comparative hybridization of PAO1 and PA14 genomes at high specificity (> 0.996). Variations larger than SNPs were detected at much higher sensitivities, reaching nearly 100% for genetic differences affecting multiple consecutive probe oligonucleotides. The detailed comparison of the in silico alignment with experimental hybridization data lead to the identification of various factors influencing sensitivity and specificity in SNP detection and to the identification of strain specific features such as a large deletion within the PA4684 and PA4685 genes in the Washington Genome Center PAO1.The application of the genome array as a tool to identify adaptive mutations, to depict genome organizations, and to identify global regulons by the "ChIP-on-chip" technique will expand our knowledge on P. aeruginosa adaptation, evolution and regulatory mechanisms of persistence on a global scale and thus advance the development of effective therapies to overcome persistent disease.Pseudomonas aeruginosa is a very versatile bacterial organism that has a unique capability to thrive and survive in a great variety of habitats. The bacterium is ubiquitously found in aquatic and terrestic environments and has evolved as an important opportunistic pathogen that causes serious infections in plants, insects and vertebrates [1,2]. In the human host P. aeruginosa is mainly a nosocomial pathogen feared for entailing acute pneumonia and sepsis accompanied with very high mortality rates [3,4]. Moreover, P. aeruginosa is a dominant bacterial pathogen that causes chronic infections in patients with burns or suffering from cystic fibrosis (CF) [5-7]. Most of the CF patients acquire P. aeruginosa from the environment during their earl
Expression QTL mapping in regulatory and helper T cells from the BXD family of strains reveals novel cell-specific genes, gene-gene interactions and candidate genes for auto-immune disease
Rudi Alberts, Hairong Chen, Claudia Pommerenke, August B Smit, Sabine Spijker, Robert W Williams, Robert Geffers, Dunja Bruder, Klaus Schughart
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-610
Abstract: We isolated Treg and Th cells from a genetically diverse family of 31 BXD type recombinant inbred strains and the fully inbred parental strains of this family--C57BL/6J and DBA/2J. Subsequently genome-wide gene expression studies were performed from the isolated Treg and Th cells. A comparative analysis of the transcriptomes of these cell populations allowed us to identify many novel differentially expressed genes. Analysis of cis- and trans-expression Quantitative Trait Loci (eQTLs) highlighted common and unique regulatory mechanisms that are active in the two cell types. Trans-eQTL regions were found for the Treg functional genes Nrp1, Stat3 and Ikzf4. Analyses of the respective QTL intervals suggested several candidate genes that may be involved in regulating these genes in Treg cells. Similarly, possible candidate genes were found which may regulate the expression of F2rl1, Ctla4, Klrb1f. In addition, we identified a focused group of candidate genes that may be important for the maintenance of self-tolerance and the prevention of allergy.Variation of expression across the strains allowed us to find many novel gene-interaction networks in both T cell subsets. In addition, these two data sets enabled us to identify many differentially expressed genes and to nominate candidate genes that may have important functions for the maintenance of self-tolerance and the prevention of allergy.Regulatory T cells (Tregs) are key modulators of immune responses in mice and humans and represent key candidates for therapeutic interventions of a broad variety of immunological diseases [1]. While reduction or functional inactivation of Tregs would be beneficial for restoration of anti-tumor immunity, selective expansion of Tregs is a promising approach for preventing autoimmunity, allergy and organ graft rejection in the transplantation setting. Initially being described as thymus-derived CD25+ subpopulation within the na?ve CD4+ T-helper cell (Th) pool [2], during the last decade e
Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype
Charlotte Gustafsson, Jenny Mj?sberg, Andreas Matussek, Robert Geffers, Leif Matthiesen, G?ran Berg, Surendra Sharma, Jan Buer, Jan Ernerudh
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002078
Abstract: Background Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.
Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
Barkha Srivastava, Paulina B?a?ejewska, Manuela He?mann, Dunja Bruder, Robert Geffers, Susanne Mauel, Achim D. Gruber, Klaus Schughart
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004857
Abstract: The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influence of the genetic background to influenza A H1N1 (PR8) and H7N7 (SC35M) viruses. The seven inbred laboratory strains of mice analyzed exhibited different weight loss kinetics and survival rates after infection with PR8. Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains. The LD50 to the influenza virus PR8 in DBA/2J mice was more than 1000-fold lower than in C57BL/6J mice. High susceptibility in DBA/2J mice was also observed after infection with influenza strain SC35M. In addition, infected DBA/2J mice showed a higher viral load in their lungs, elevated expression of cytokines and chemokines, and a more severe and extended lung pathology compared to infected C57BL/6J mice. These findings indicate a major contribution of the genetic background of the host to influenza A virus infections. The overall response in highly susceptible DBA/2J mice resembled the pathology described for infections with the highly virulent influenza H1N1-1918 and newly emerged H5N1 viruses.
The Pseudomonas aeruginosa Transcriptome in Planktonic Cultures and Static Biofilms Using RNA Sequencing
Andreas D?tsch, Denitsa Eckweiler, Monika Schniederjans, Ariane Zimmermann, Vanessa Jensen, Maren Scharfe, Robert Geffers, Susanne H?ussler
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031092
Abstract: In this study, we evaluated how gene expression differs in mature Pseudomonas aeruginosa biofilms as opposed to planktonic cells by the use of RNA sequencing technology that gives rise to both quantitative and qualitative information on the transcriptome. Although a large proportion of genes were consistently regulated in both the stationary phase and biofilm cultures as opposed to the late exponential growth phase cultures, the global biofilm gene expression pattern was clearly distinct indicating that biofilms are not just surface attached cells in stationary phase. A large amount of the genes found to be biofilm specific were involved in adaptation to microaerophilic growth conditions, repression of type three secretion and production of extracellular matrix components. Additionally, we found many small RNAs to be differentially regulated most of them similarly in stationary phase cultures and biofilms. A qualitative analysis of the RNA-seq data revealed more than 3000 putative transcriptional start sites (TSS). By the use of rapid amplification of cDNA ends (5′-RACE) we confirmed the presence of three different TSS associated with the pqsABCDE operon, two in the promoter of pqsA and one upstream of the second gene, pqsB. Taken together, this study reports the first transcriptome study on P. aeruginosa that employs RNA sequencing technology and provides insights into the quantitative and qualitative transcriptome including the expression of small RNAs in P. aeruginosa biofilms.
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