Correlative controls (influences of one organ over another organ) of seeds over maternal growth are one of the most obvious phenotypic expressions of the trade-off between growth and reproduction. However, the underlying molecular mechanisms are largely unknown. Here, we characterize the physiological and molecular effects of correlative inhibition by seeds on Arabidopsis thaliana inflorescences, i.e. global proliferative arrest (GPA) during which all maternal growth ceases upon the production of a given number of seeds. We use laser-assisted microdissection and RNA-seq or Affymetrix GeneChip hybridizations to compare sterile growing, fertile growing and fertile arrested meristems or whole inflorescences. In shoot tissues, we detected the induction of stress- and senescence-related gene expression upon fruit production and GPA, and a drop in chlorophyll levels - suggestive of altered source-sink relationships between vegetative shoot and reproductive tissues. Levels of shoot reactive oxygen species, however, strongly decreased upon GPA - a phenomenon that is associated with bud dormancy in some perennials. Indeed, gene expression changes in arrested apical inflorescences after fruit removal resembled changes observed in axillary buds following release from apical dominance. This suggests that GPA represents a form of bud dormancy, and that dominance is gradually transferred from growing inflorescences to maturing seeds - allowing offspring control over maternal resources, simultaneously restricting offspring number.
Seed Production Affects Maternal Growth and Senescence in Arabidopsis.
No sample metadata fields
View SamplesSepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to determine if the pathogen is bacterial, fungal or neither of the two. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97%) for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83%) for an additional dataset comprising Cryptococcus neoformans infections. Furthermore, the noise-robustness of the classifier suggests high rates of correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.
Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study.
Sex, Specimen part, Subject, Time
View SamplesCarnitine is a water soluble quaternary amine which is essential for normal function of all tissues.
Effect of L-carnitine on the hepatic transcript profile in piglets as animal model.
Sex, Age, Specimen part
View SamplesThe purpose of this study was to characterize the transcriptional effects induced by intramuscular IFN-beta-1a treatment (Avonex, 30 g once weekly) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 24 MS patients within the first four weeks of IFN-beta administration.
Network analysis of transcriptional regulation in response to intramuscular interferon-β-1a multiple sclerosis treatment.
Sex
View SamplesBackground
Adapted Boolean network models for extracellular matrix formation.
Sex, Age
View SamplesHuman fibroblasts at different population doublings were treated with low amounts of rotenone (mild stress) and compared to untreated fibroblasts. Two different cell lines were used (MRC-5, HFF). Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 60 samples: 3 biological replicates for each group: MRC-5 cells at 4 different population doublings (PD) with and without rotenone; HFF cells at 6 different population doublings with and without rotenone
Hormetic effect of rotenone in primary human fibroblasts.
No sample metadata fields
View SamplesBackground. Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease, characterized by overexpression of pro-inflammatory/-destructive genes and other activating genes (e.g., proto-oncogenes) in the synovial membrane (SM). The gene expression in disease is often characterized by significant inter-individual variances via specific synchronization/ desynchronization of gene expression. To elucidate the contribution of the variance to the pathogenesis of disease, expression variances were tested in SM samples of RA patients, osteoarthritis (OA) patients, and normal controls (NC).
Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane.
Sex, Age, Disease
View SamplesTwo biological replicate experiments were performed to estimate the bias of the gene expression pattern of infected and non-infected HEp-2 cells. Microarrays hybridized with RNA from 2 h of non-infected HEp-2 cells were used as reference chips for the comparison with microarrays hybridized with RNA from 2 h and 4 h of eukaryotic cells exposed to wt-bacteria and .fasX-mutant. As a reference for chips hybridized with RNA prepared from 6 h p. i. and 8 h p. i. of both GAS-infected HEp-2 cells we used chips that were hybridized with RNA isolated from non-infected cells 8 h p. i. We also compared the microarray data from 2 h of non-infected HEp-2 cells with those from 8 h of non-infected HEp-2 cells to determine the influence of the extended culture on the non-infected cells. Only such genes which were differentially regulated after infection with wt-bacteria and .fasX-mutant infected cells and not differentially present in unequal amounts between the 2 h and 8 h of controls were included in the subsequent statistical analysis.
Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness.
Disease, Disease stage, Cell line, Time
View SamplesInflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Treatment options are limited and the mechanisms underlying its aggressiveness are poorly understood. Intermittent hypoxia (IH) causes oxidative stress and is emerging as important regulator of tumor metastasis. Vessels in IBC tumors were shown to be immature, which is a primary cause of IH. We therefore investigated the relevance of IH for the modulation of gene expression in IBC cells in order to assess IH as potential regulator of IBC aggressiveness. Gene array analysis of IBC cells following chronic IH (45-60 days) demonstrated increased expression of pro-metastatic genes of the extracellular matrix, such as tenascin-C (TNC; an essential factor of the metastatic niche) and matrix metalloproteinase 9 (MMP9), and of pro-inflammatory processes, such as cyclooxygenase-2 (COX-2). Investigating the oxidative stress-dependent regulation of TNC, we found a gradual sensitivity on mRNA and protein levels. Oxidative stress activated NF-E2-related factor 2 (Nrf2), c-Jun N-terminal kinase (JNK), c-Jun and nuclear factor B (NF-B), but TNC upregulation was only dependent on NF-B activation. Pharmacological inhibition of inhibitor of NF-B (IB) phosphorylation as well as overexpression of IB prevented TNC, MMP9 and COX-2 induction, whereas the pro-inflammatory cytokine interleukin-1 (IL-1) increased their expression levels. Analysis of the gene array data showed NF-B binding sites for 64% of all upregulated genes, linking NF-B and IH-dependent regulation of pro-metastatic gene expression in IBC cells. Our results provide a first link between intermittent hypoxia and pro-metastatic gene expression in IBC cells, revealing a putative novel mechanism for the high metastatic potential of IBC.
Intermittent hypoxia confers pro-metastatic gene expression selectively through NF-κB in inflammatory breast cancer cells.
No sample metadata fields
View SamplesSynovial fibroblasts of 6 RA patients were treated with IL1 or PDGF-D. The aim of this study was to outline mechanism of the disease RA by a treatment with one of these cytokines.
Novel application of multi-stimuli network inference to synovial fibroblasts of rheumatoid arthritis patients.
Treatment, Subject, Time
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