Similar Datasets
Project description:Proteoglycan glycosaminoglycan (GAG) chains are attached to a serine residue in the protein through a linkage series of sugars, the first of which is xylose. Xylosides are chemicals which compete with the xylose at the enzyme xylosyl transferase to prevent the attachment of GAG chains to proteins. These compounds have been employed at concentrations in the millimolar range as tools to study the role of GAG chains in proteoglycan function. In the course of our studies with xylosides, we conducted a dose-response curve for xyloside actions on neural cells. To our surprise, we found that concentrations of xylosides in the nanomolar to micromolar range had major effects on cell morphology of hippocampal neurons as well as of Neuro2a cells, affecting both actin and tubulin cytoskeletal dynamics. Such effects/morphological changes were not observed with higher xyloside concentrations. We found a dose-dependent alteration of GAG secretion by Neuro2a cells; however, concentrations of xylosides which were effective in altering neuronal morphology did not cause a large change in the rate of GAG chain secretion. In contrast, both low and high concentrations of xylosides altered HS and CS composition. RNAseq of treated cells demonstrated alterations in gene expression only after treatment with millimolar concentration of xylosides that had no effect on cell morphology. These observations support a novel action of xylosides on neuronal cells.
| S-EPMC9239447 | biostudies-literature
Project description:A Novel Cytoskeletal Action of Xylosides
| PRJNA848934 | ENA
Project description:The zebrafish embryotoxicity test (ZET) is considered as a useful alternative model in predictive toxicology. Currently, morphological assessment of the embryo is the main readout for this assay. However, implementation of transcriptomics may help to detect more subtle effects which may increase the sensitivity and predictability of the test. Most transcriptomics studies to date have used only a single toxicant concentration, generally selected based on the sensitivity of the classical morphological endpoint. However, effects on morphology and gene expression are dependent on compound concentration, which consequently may influence prediction of developmental toxicity. In this study, we tested a concentration-response of flusilazole in the ZET. At 24 hours post fertilization, microarray analysis revealed a number of processes to be regulated in a concentration-dependent way. We identified development related processes, retinol metabolism and transcription, as well as processes corresponding to the anti-fungal mechanism of action, steroid biosynthesis and fatty acid metabolism, to be differentially regulated. Retinol metabolism and transcription were already significantly altered at concentrations that were not inducing morphological effects. Differential expression of genes related to steroid biosynthesis and fatty acid metabolism showed a concentration-response similar to morphology. An increase in concentration was also positively associated with an increase in magnitude of expression for each individual gene. Our study shows that transcriptomics analysis in the ZET is a more sensitive readout of compound-induced effects than morphological assessment. However, the interpretation of differential gene expression in terms of predicting morphological effects is not straightforward and requires further study.
2012-03-21 | E-MTAB-832 | biostudies-arrayexpress
Project description:Screening of various bisquaternary bisnaphthalimides against a variety of human pathogens revealed one compound, designated MT02, with strong inhibitory effects against gram-positive bacteria. The minimal inhibitory concentrations ranged from 0.31 µg/ml against community-acquired methicillin resistant Staphylococcus aureus (MRSA) strain USA300 to 20 µg/ml against Streptococcus pneumonia. DNA-microarray studies generated a transcriptional signature characterized by a strong increase of genes involved in DNA-metabolism, DNA-replication, SOS-response and transport of positively charged compounds. Radioactive whole cell labeling experiments indicated a strong impact of MT02 on bacterial DNA-replication. Furthermore, surface plasmon resonance and gel retardation experiments demonstrated direct binding of MT02 to DNA in a concentration dependent, reversible and sequence-unspecific manner. The data presented suggest that the bisquaternary bisnaphthalimide MT02 exerts anti-gram-positive activity by binding to DNA and thereby prohibiting appropriate DNA-replication. WT strain exposed to MT02 for 60 minutes in rich medium
2011-01-04 | E-GEOD-23077 | biostudies-arrayexpress
Project description:Screening of various bisquaternary bisnaphthalimides against a variety of human pathogens revealed one compound, designated MT02, with strong inhibitory effects against gram-positive bacteria. The minimal inhibitory concentrations ranged from 0.31 µg/ml against community-acquired methicillin resistant Staphylococcus aureus (MRSA) strain USA300 to 20 µg/ml against Streptococcus pneumonia. DNA-microarray studies generated a transcriptional signature characterized by a strong increase of genes involved in DNA-metabolism, DNA-replication, SOS-response and transport of positively charged compounds. Radioactive whole cell labeling experiments indicated a strong impact of MT02 on bacterial DNA-replication. Furthermore, surface plasmon resonance and gel retardation experiments demonstrated direct binding of MT02 to DNA in a concentration dependent, reversible and sequence-unspecific manner. The data presented suggest that the bisquaternary bisnaphthalimide MT02 exerts anti-gram-positive activity by binding to DNA and thereby prohibiting appropriate DNA-replication.
2011-01-04 | GSE23077 | GEO
Project description:PrPC-dependent gene expression and cell signalling signature in Neuro2a cells. Role on mitogenic stimulation and cell morphology.
| PRJNA169139 | ENA
Project description:The roles of histone demethylase KDM7 in gene expression were analyzed by gene expression profiling experiments with mouse neuroblastoma cell line Neuro2A. Keywords: mouse neuroblastoma, Neuro2A, gene expression profiling, microarray, Affimetrix M430 2.0 chip In order to examine the effect of KDM7 in gene expression, we generated stable KDM7 knockdown cell lines in mouse neuroblastoma cell line Neuro2A. Total RNAs were extracted from 5 cell lines (parental cells: Neuro2A, empty vector: Neuro2A transfected with empty vector, EGFP KD: Neuro2A transfected with vector for EGFP knock down, KDM7 KD1: Neuro2A transfected with vector 1 for KDM7 knock down, and KDM7 KD2: Neuro2A transfected with vector 2 for KDM7 knock down) and analyzed for gene expression profiles using Affymetrix platform.
2010-03-06 | E-GEOD-17494 | biostudies-arrayexpress
Project description:Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis, however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TFmediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MTbased arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture and are grouped into three major phenotypic categories, based upon neuromorphometric analyses:¬¬ complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation.
2017-10-10 | GSE83938 | GEO
Project description:Age-dependent modifications of the germ cells epigenome remain poorly understood. Our objective was to assess the DNA methylation profile of human spermatozoa during aging. A cohort study was designed to investigate the effects of age and fertility status on sperm DNA methylation.
| EGAS00001004168 | EGA
Project description:We compared the gene expression in untransfected Neuro2A cells and in pCDNA3.1myc/his vector transfected Neuro2A cells
2012-02-29 | GSE36142 | GEO