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Global Gene Expression (global + gene_expression)
Terms modified by Global Gene Expression Selected AbstractsGene Expression Profiling in Cluster Headache: A Pilot Microarray StudyHEADACHE, Issue 10 2006Christina Sjöstrand MD Background.,Cluster headache (CH) is a primary neurovascular headache disorder characterized by attacks of excruciating pain accompanied by ipsilateral autonomic symptoms. CH pathophysiology is presumed to involve an activation of hypothalamic and trigeminovascular systems, but inflammation and immunological mechanisms have also been hypothesized to be of importance. Objective.,To identify differentially expressed genes during different clinical phases of CH, assuming that changes of pathophysiological importance would also be seen in peripheral venous blood. Methods.,Blood samples were drawn at 3 consecutive occasions from 3 episodic CH patients: during attacks, between attacks and in remission, and at 1 occasion from 3 matched controls. Global gene expression was analyzed with microarray tehnology using the Affymetrix Human Genome U133 2.0 Plus GeneChip® Set, covering more than 54,000 gene transcripts, corresponding to almost 22,000 genes. Quantitative RT-PCR on S100P gene expression was analyzed in 6 patients and 14 controls. Results.,Overall, quite small differences were seen intraindividually and large differences interindividually. However, pairwise comparisons of signal values showed upregulation of several S100 calcium binding proteins; S100A8 (calgranulin A), S100A12 (calgranulin C), and S100P during active phase of the disease compared to remission. Also, annexin A3 (calcium-binding) and ICAM3 showed upregulation. BIRC1 (neuronal apoptosis inhibitory protein), CREB5, HLA-DQA1, and HLA-DQB1 were upregulated in patients compared to controls. The upregulation of S100P during attack versus remission was confirmed by quantitative RT-PCR analysis. Conclusions.,The S100A8 and S100A12 proteins are considered markers of non-infectious inflammatory disease, while the function of S100P is still largely unknown. Furthermore, upregulation of HLA-DQ genes in CH patients may also indicate an inflammatory response. Upregulation of these pro-inflammatory genes during the active phase of CH has not formerly been reported. Data from this pilot microarray study provide a basis for further studies in CH. [source] Regulation of global gene expression in the bone marrow microenvironment by androgen: Androgen ablation increases insulin-like growth factor binding protein-5 expressionTHE PROSTATE, Issue 15 2007Chang Xu Abstract BACKGROUND Prostate cancer frequently metastasizes to bone. Androgen suppression treatment is initially highly effective, but eventually results in resistant cancer cells. This study evaluates the effects of androgen suppression on the bone and bone marrow (BM). In particular we questioned whether the androgen therapy could adversely facilitate prostate cancer progression through an increase growth factor secretion by the bone microenvironment. METHODS Global gene expression is analyzed on mPEDB DNA microarrays. Insulin-like growth factor binding protein-5 (IGFBP5) is detected by immunohistochemistry in mouse tissues and its regulation measured by qPCR and Western blotting in human BM stromal cells. Effects of extracellular matrix-associated IGFBP5 on human prostate epithelial cells are tested in an MTS cell-growth assay. RESULTS Castration increases expression of 159 genes (including 4 secreted cytokines) and suppresses expression of 84 genes. IGFBP5 is most consistently increased and the increase in expression is reversed by testosterone administration. IGFBP5 protein is detected in vivo in osteoblasts, BM stromal cells, and endothelial cells. Primary human stromal cell cultures secrete IGFBP5. In vitro, treatment of immortalized human marrow stromal cells with charcoal-stripped serum increases IGFBP5 mRNA expression, which is reversed by androgen supplementation. IGFBP5 is incorporated into the extracellular matrix. Further, IGFBP5 immobilized on extracellular matrices of stromal cells enhances the growth of immortalized prostate epithelial cells. CONCLUSIONS Androgen suppressive therapy increases IGFBP5 in the BM microenvironment and thereby may facilitate the progression of prostate cancer. Prostate 67: 1621,1629, 2007. © 2007 Wiley-Liss, Inc. [source] Identification of candidate genes involved in the radiosensitivity of esophageal cancer cells by microarray analysisDISEASES OF THE ESOPHAGUS, Issue 4 2008R. Ogawa SUMMARY., Radiotherapy plays a key role in the control of tumor growth in esophageal cancer patients. To identify the patients who will benefit most from radiation therapy, it is important to know the genes that are involved in the radiosensitivity of esophageal cancer cells. Hence, we examined the global gene expression in radiosensitive and radioresistant esophageal squamous cell carcinoma cell lines. Radiosensitivities of 13 esophageal cancer cell lines were measured. RNA was extracted from each esophageal cancer cell line and a normal esophageal epithelial cell line, and the global gene expression profiles were analyzed using a 34 594-spot oligonucleotide microarray. In the clonogenic assay, one cell line (TE-11) was identified to be highly sensitive to radiation, while the other cell lines were found to be relatively radioresistant. We identified 71 candidate genes that were differentially expressed in TE-11 by microarray analysis. The up-regulated genes included CABPR, FABP5, DSC2, GPX2, NME, CBR3, DOCK8, and ABCC5, while the down-regulated genes included RPA1, LDOC1, NDN, and SKP1A. Our investigation provided comprehensive information on genes related to radiosensitivity of esophageal cancer cells; this information can serve as a basis for further functional studies. [source] Lack of CbrB in Pseudomonas putida affects not only amino acids metabolism but also different stress responses and biofilm developmentENVIRONMENTAL MICROBIOLOGY, Issue 6 2010Cristina I. Amador Summary The CbrAB two-component system has been described in certain species of Pseudomonads as a global regulatory system required for the assimilation of several amino acids (e.g. histidine, proline or arginine) as carbon or carbon and nitrogen sources. In this work, we used global gene expression and phenotypic analyses to characterize the roles of the CbrAB system in Pseudomonas putida. Our results show that CbrB is involved in coordination with the nitrogen control system activator, NtrC, in the uptake and assimilation of several amino acids. In addition, CbrB affects other carbon utilization pathways and a number of apparently unrelated functions, such as chemotaxis, stress tolerance and biofilm development. Based on these new findings, we propose that CbrB is a high-ranked element in the regulatory hierarchy of P. putida that directly or indirectly controls a variety of metabolic and behavioural traits required for adaptation to changing environmental conditions. [source] Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P450 1A activity, and plasma phosphate in fish,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2009Lina Gunnarsson Abstract Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for 5 d. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sublethal toxicity, as well as illuminate possible causative agents. [source] The effect of hfq on global gene expression and virulence in Neisseria gonorrhoeaeFEBS JOURNAL, Issue 19 2009Manuela Dietrich Hfq is an RNA chaperone that functions as a pleiotropic regulator for RNA metabolism in bacteria. In several pathogenic bacteria, Hfq contributes indirectly to virulence by binding to riboregulators that modulate the stability or translation efficiency of RNA transcripts. To characterize the role of Hfq in the pathogenicity of Neisseria gonorrhoeae, we generated an N. gonorrhoeae hfq mutant. Infectivity and global changes in gene expression caused by the hfq mutation in N. gonorrhoeae strain MS11 were analyzed. Transcriptional analysis using a custom-made N. gonorrhoeae microarray revealed that 369 ORFs were differentially regulated in the hfq mutant, MS11hfq, in comparison with the wild-type strain (202 were upregulated, and 167 were downregulated). The loss-of-function mutation in hfq led to pleiotropic phenotypic effects, including an altered bacterial growth rate and reduced adherence to epithelial cells. Twitching motility and microcolony formation were not affected. Hfq also appears to play a minor role in inducing the inflammatory response of infected human epithelial cells. Interleukin-8 production was slightly decreased, and activation of c-Jun N-terminal kinase, a mitogen-activated protein kinase, was reduced in MS11hfq- infected epithelial cells in comparison with wild type-infected cells. However, activation of nuclear factor kappa B, extracellular signal-regulated kinase 1/2 and p38 remained unchanged. The data presented suggest that Hfq plays an important role as a post-transcriptional regulator in N. gonorrhoeae strain MS11 but does not contribute significantly to its virulence in cell culture models. [source] Frequent decreased expression of candidate tumor suppressor gene, DEC1, and its anchorage-independent growth properties and impact on global gene expression in esophageal carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Alfred Chi Chung Leung Abstract Previous studies showed that expression of the novel candidate tumor suppressor gene, DEC1 (Deleted in Esophageal Cancer 1), is reduced in esophageal carcinoma and suppresses cancer cell growth in vitro and tumor growth in vivo in nude mice. This study shows that DEC1 gene expression was downregulated in 100% of 16 esophageal squamous cell carcinoma (ESCC) cell lines and 52 and 45%, respectively, of esophageal tumor specimens from Hong Kong and a high-risk ESCC region of Henan, China. Using epitope tagging, the DEC1 protein was localized to both the cytoplasm and nucleus of the cell. In 3D Matrigel culture, no significant difference in colony numbers formed was observed for DEC1 stable transfectants, as compared to vector-alone transfectant controls. However, significantly smaller colony sizes were observed for the DEC1 transfectants. In in vitro cell migration, invasion and soft agar assays of DEC1 transfectants, only the soft agar assay showed statistically significant differences in colony numbers with the vector-alone controls, indicating that DEC1 may be involved in anchorage-independent cell growth. In addition, the global gene expression affected by DEC1 in tumor-suppressive stable transfectants was investigated using cDNA oligonucleotide microarray hybridization. Three candidate genes, TFPI-2, GDF15 and DUSP6, were identified through this approach; they are downregulated in tumor segregants of DEC1 stable transfectants, ESCC cell lines and esophageal tumors and have a potential role in tumor growth and progression. These studies show that DEC1 is involved in esophageal cancer development and help elucidate its functional role in tumor development. © 2007 Wiley-Liss, Inc. [source] Generation of pluripotent stem cells from eggs of aging miceAGING CELL, Issue 2 2010Junjiu Huang Summary Oocytes can reprogram genomes to form embryonic stem (ES) cells. Although ES cells largely escape senescence, oocytes themselves do senesce in the ovaries of most mammals. It remains to be determined whether ES cells can be established using eggs from old females, which exhibit reproductive senescence. We attempted to produce pluripotent stem cell lines from artificial activation of eggs (also called pES) from reproductive aged mice, to determine whether maternal aging affects pES cell production and pluripotency. We show that pES cell lines were generated with high efficiency from reproductive aged (old) mice, although parthenogenetic embryos from these mice produced fewer ES clones by initial two passages. Further, pES cell lines generated from old mice showed telomere length, expression of pluripotency molecular markers (Oct4, Nanog, SSEA1), alkaline phosphatase activity, teratoma formation and chimera production similar to young mice. Notably, DNA damage was reduced in pES cells from old mice compared to their progenitor parthenogenetic blastocysts, and did not differ from that of pES cells from young mice. Also, global gene expression differed only minimally between pES cells from young and old mice, in contrast to marked differences in gene expression in eggs from young and old mice. These data demonstrate that eggs from old mice can generate pluripotent stem cells, and suggest that the isolation and in vitro culture of ES cells must select cells with high levels of DNA and telomere integrity, and/or with capacity to repair DNA and telomeres. [source] Genes Associated With Alcohol Abuse and Tobacco Smoking in the Human Nucleus Accumbens and Ventral Tegmental AreaALCOHOLISM, Issue 7 2010Traute Flatscher-Bader Background:, The incidence of alcohol and tobacco co-abuse is as high as 80%. The molecular mechanism underlying this comorbidity is virtually unknown, but interactions between these drugs have important implications for the development of and recovery from drug dependence. Methods:, We investigated the effects of chronic tobacco and alcohol abuse and the interaction of the 2 behaviors on global gene expression in the human nucleus accumbens using cDNA microarrays and 20 alcoholic and control cases, with and without smoking comorbidity. Changes in gene expression were established by factorial ANOVA. Unsupervised hierarchical clustering was utilized to probe the strength of the data sets. Applying real-time PCR differential expression of candidate genes was confirmed in the nucleus accumbens and explored further in a second core region of the mesolimbic system, the ventral tegmental area. Results:, Subjecting the data sets derived from microarray gene expression screening to unsupervised hierarchical clustering tied the cases into distinct groups. When considering all alcohol-responsive genes, alcoholics were separated from nonalcoholics with the exception of 1 control case. All smokers were distinguished from nonsmokers based on similarity in expression of smoking-sensitive genes. In the nucleus accumbens, alcohol-responsive genes were associated with transcription, lipid metabolism, and signaling. Smoking-sensitive genes were predominantly assigned to functional groups concerned with RNA processing and the endoplasmic reticulum. Both drugs influenced the expression of genes involved in matrix remodeling, proliferation, and cell morphogenesis. Additionally, a gene set encoding proteins involved in the canonical pathway "regulation of the actin cytoskeleton" was induced in response to alcohol and tobacco co-abuse and included. Alcohol abuse elevated the expression of candidate genes in this pathway in the nucleus accumbens and ventral tegmental area, while smoking comorbidity blunted this induction in the ventral tegmental area. Conclusions:, The region-specific modulation of alcohol-sensitive gene expression by smoking may have important consequences for alcohol-induced aberrations within the mesolimbic dopaminergic system. [source] Genome-wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stressMOLECULAR MICROBIOLOGY, Issue 1 2009Brice Enjalbert Summary Candida albicans is more pathogenic than Candida dubliniensis. However, this disparity in virulence is surprising given the high level of sequence conservation and the wide range of phenotypic traits shared by these two species. Increased sensitivity to environmental stresses has been suggested to be a possible contributory factor to the lower virulence of C. dubliniensis. In this study, we investigated, in the first comparison of C. albicans and C. dubliniensis by transcriptional profiling, global gene expression in each species when grown under conditions in which the two species exhibit differential stress tolerance. The profiles revealed similar core responses to stresses in both species, but differences in the amplitude of the general transcriptional responses to thermal, salt and oxidative stress. Differences in the regulation of specific stress genes were observed between the two species. In particular, ENA21, encoding a sodium ion transporter, was strongly induced in C. albicans but not in C. dubliniensis. In addition, ENA21 was identified in a forward genetic screen for C. albicans genomic sequences that increase salt tolerance in C. dubliniensis. Introduction of a single copy of CaENA21 was subsequently shown to be sufficient to confer salt tolerance upon C. dubliniensis. [source] Signaling pathways in osteoblast proinflammatory responses to infection by Porphyromonas gingivalisMOLECULAR ORAL MICROBIOLOGY, Issue 2 2008T. Ohno Introduction:, We recently investigated global gene expression in ST2 mouse stromal cells infected by the periodontal pathogen Porphyromonas gingivalis using microarray technology, and found that the bacterium induces a wide range of proinflammatory gene expression. Here, we reported the signaling pathways involved in those proinflammatory responses. Methods:, ST2 cells and primary calvarial osteoblasts from C3H/HeN, C57BL/6, and MyD88-deficient (MyD88,/,) mice were infected with P. gingivalis ATCC33277 and its gingipain-deficient mutant KDP136. Expression of the chemokines CCL5 and CXCL10, and matrix metalloproteinase-9 (MMP9) were quantified by real-time polymerase chain reaction, while phosphorylation of protein kinases and degradation of an inhibitor of nuclear factor-,B, I,B-,, were detected by Western blotting, and activation of transcriptional factors was determined by a luciferase reporter assay. The effects of inhibitors of transcriptional factors and protein kinases were also investigated. Results:, Infection by P. gingivalis elicited gene expression of CCL5, CXCL10, and MMP9 in both ST2 cells and osteoblasts. Western blot and reporter assay results revealed activation of nuclear factor-,B (NF-,B) and activator protein-1 transcription factors. The NF-,B inhibitor suppressed the expression of CCL5 and MMP9, but not that of CXCL10, whereas P. gingivalis infection induced significant CCL5 expression in MyD88,/, osteoblasts. In addition, activation of protease-activated receptors by trypsin elicited significant induction of CXCL10. Conclusion:, Our results suggest that various proinflammatory responses in P. gingivalis -infected stromal/osteoblast cells are NF-,B-dependent, but not always dependent on the Toll-like receptor/MyD88 pathway, while some responses are related to the activation of protease-activated receptors. Thus, P. gingivalis does not fully utilize well-established pathogen recognition molecules such as Toll-like receptors. [source] Comparison of global gene expression between porcine testis tissue xenografts and porcine testis in situMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 6 2007Wenxian Zeng Abstract Testis tissue from immature mammalian donor animals, grafted ectopically to immunodeficient mouse hosts, can undergo complete spermatogenesis with the production of fertilization-competent spermatozoa. To further characterize testis tissue xenografts as a model for testis function in situ, the objective of this study was to compare gene expression between porcine testis tissue xenografts and testis tissue in situ. Pieces of testis tissue from 1-week-old piglets were grafted onto immunodeficient male mice and a littermate piglet was raised for comparison as control. Complete spermatogenesis was present in the testis tissue xenografts at 8 months after transplantation into mouse hosts and in the 8-month-old control porcine testis tissue. Total RNA was isolated from xenografts and control tissue, and the RNA was labeled and hybridized to the porcine genome array. By analyzing the expression of 23,256 transcripts, we found that 71 genes were differentially expressed with at least a fourfold difference between xenografts and control tissue. Interestingly, none of the 56 transcripts present on the array that were annotated in porcine testis showed differential expression between xenografts and control testis. This analysis indicates that global gene expression in porcine testis xenografts appears comparable to testis tissue in situ. These findings support the hypothesis that testis tissue xenografts can provide a representative model to study mammalian spermatogenesis. Mol. Reprod. Dev. 74: 674,679, 2007. © 2006 Wiley-Liss, Inc. [source] Global gene expression profile of Orientia tsutsugamushiPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2010Bon-A Cho Abstract Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of Scrub typhus. The control mechanisms for bacterial gene expression are largely unknown. Here, the global gene expression of O. tsutsugamushi within eukaryotic cells was examined using a microarray and proteomic approaches for the first time. These approaches identified 643 genes, corresponding to approximately 30% of the genes encoded in the genome. The majority of expressed genes belonged to several functional categories including protein translation, protein processing/secretion, and replication/repair. We also searched the conserved sequence blocks (CSBs) in the O. tsutsugamushi genome which is unique in that up to 40% of its genome consists of dispersed repeated sequences. Although extensive shuffling of genomic sequences was observed between two different strains, 204 CSBs, covering 48% of the genome, were identified. When combining the data of CSBs and global gene expression, the CSBs correlates well with the location of expressed genes, suggesting the functional conservation between gene expression and genomic location. Finally, we compared the gene expression of the bacteria-infected fibroblasts and macrophages using microarray analysis. Some major changes were the downregulation of genes involved in translation, protein processing and secretion, which correlated with the reduction in bacterial translation rates and growth within macrophages. [source] Seed after-ripening is a discrete developmental pathway associated with specific gene networks in ArabidopsisTHE PLANT JOURNAL, Issue 2 2008Esther Carrera Summary After-ripening (AR) is a time and environment regulated process occurring in the dry seed, which determines the germination potential of seeds. Both metabolism and perception of the phytohormone abscisic acid (ABA) are important in the initiation and maintenance of dormancy. However, molecular mechanisms that regulate the capacity for dormancy or germination through AR are unknown. To understand the relationship between ABA and AR, we analysed genome expression in Arabidopsis thaliana mutants defective in seed ABA synthesis (aba1-1) or perception (abi1-1). Even though imbibed mutant seeds showed no dormancy, they exhibited changes in global gene expression resulting from dry AR that were comparable with changes occurring in wild-type (WT) seeds. Core gene sets were identified that were positively or negatively regulated by dry seed storage. Each set included a gene encoding repression or activation of ABA function (LPP2 and ABA1, respectively), thereby suggesting a mechanism through which dry AR may modulate subsequent germination potential in WT seeds. Application of exogenous ABA to after-ripened WT seeds did not reimpose characteristics of freshly harvested seeds on imbibed seed gene expression patterns. It was shown that secondary dormancy states reinstate AR status-specific gene expression patterns. A model is presented that separates the action of ABA in seed dormancy from AR and dry storage regulated gene expression. These results have major implications for the study of genetic mechanisms altered in seeds as a result of crop domestication into agriculture, and for seed behaviour during dormancy cycling in natural ecosystems. [source] Regulation of global gene expression in the bone marrow microenvironment by androgen: Androgen ablation increases insulin-like growth factor binding protein-5 expressionTHE PROSTATE, Issue 15 2007Chang Xu Abstract BACKGROUND Prostate cancer frequently metastasizes to bone. Androgen suppression treatment is initially highly effective, but eventually results in resistant cancer cells. This study evaluates the effects of androgen suppression on the bone and bone marrow (BM). In particular we questioned whether the androgen therapy could adversely facilitate prostate cancer progression through an increase growth factor secretion by the bone microenvironment. METHODS Global gene expression is analyzed on mPEDB DNA microarrays. Insulin-like growth factor binding protein-5 (IGFBP5) is detected by immunohistochemistry in mouse tissues and its regulation measured by qPCR and Western blotting in human BM stromal cells. Effects of extracellular matrix-associated IGFBP5 on human prostate epithelial cells are tested in an MTS cell-growth assay. RESULTS Castration increases expression of 159 genes (including 4 secreted cytokines) and suppresses expression of 84 genes. IGFBP5 is most consistently increased and the increase in expression is reversed by testosterone administration. IGFBP5 protein is detected in vivo in osteoblasts, BM stromal cells, and endothelial cells. Primary human stromal cell cultures secrete IGFBP5. In vitro, treatment of immortalized human marrow stromal cells with charcoal-stripped serum increases IGFBP5 mRNA expression, which is reversed by androgen supplementation. IGFBP5 is incorporated into the extracellular matrix. Further, IGFBP5 immobilized on extracellular matrices of stromal cells enhances the growth of immortalized prostate epithelial cells. CONCLUSIONS Androgen suppressive therapy increases IGFBP5 in the BM microenvironment and thereby may facilitate the progression of prostate cancer. Prostate 67: 1621,1629, 2007. © 2007 Wiley-Liss, Inc. [source] Microarray Studies in Bacillus subtilisBIOTECHNOLOGY JOURNAL, Issue 7 2009nar Kocaba Abstract This review focuses on the construction of a global, comprehensive understanding of Bacillus subtilis through microarray studies. The microarray studies in B. subtilis were analysed based on the theme of the work, by mentioning the growth media, bioreactor operation conditions, RNA isolation method, number of data points analysed in exponential or stationary phases, compared genotypes, induction and repression ratios, investigated gene(s) and their positive and/or negative influences. Based on the theme and scope of the studies, the articles were reviewed under seven thematic sections, i.e., effects of gene deletion(s) or overexpression, effects of overexression of heterologous genes, comparison of global gene expression between aerobic and anaerobic respiration, effects of temperature change, effects of transported molecules, effects of limitations and stress conditions, and other microarray studies in B. subtilis. [source] | ||||||||||||||||