Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here we demonstrate that inactivation of a central regulator of iron homeostasis (fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated a substantial reorganization of the Fur regulon in response to antibiotic treatment. We hypothesized that the impact of Fur on evolvability under antibiotic pressure is due to the elevated intracellular concentration of free iron and the consequent enhancement of oxidative damage-induced mutagenesis. In agreement with expectations, over-expression of iron storage proteins, inhibition of iron transport, or anaerobic conditions drastically suppressed the evolution of resistance, while inhibition of the SOS response-mediated mutagenesis had no such effect in fur deficient population. In sum, our work revealed the central role of iron metabolism in de novo evolution of antibiotic resistance, a pattern that could influence the development of novel antimicrobial strategies.
Perturbation of iron homeostasis promotes the evolution of antibiotic resistance.
No sample metadata fields
View SamplesThe transition of regularly cycling endometrium from the proliferative or Estrogen-dominant phase of the menstrual cycle to the Progesterone-dominant Early and Mid Secretory phases requires wide-spread changes in gene expression that shift the endometrium from a proliferative capacity to a differentiated 'decidual' phenotype in preparation for implantation. This process appears delayed in women with severe endometriosis, suggestive of a progesterone resistant endometrium in this disease.
Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.
No sample metadata fields
View SamplesA predictive gene list for response to high dose melphalan therapy in patients diagnosed with multiple myeloma is generated by combining results from dose response experiments and microarray data using a B-cell line panel and the introduction of multivariate regression techniques.
Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines.
Cell line
View SamplesHuman oviduct serves as a conduit for sperm in the peri-ovulatory phase and to nurture and facilitate transport of the developing embryo en route to the uterus for subsequent nidation during the luteal phase of the cycle. Interactions between the embryo and oviductal epithelial surface proteins and secreted products during the four day embryo transit are largely undefined. Herein, we have investigated gene expression in human oviduct in the early luteal vs. follicular phase to identify candidate genes and biomolecular processes that may participate in maturation and transport of the embryo as it traverses this tissue. Oviductal RNA was isolated, processed, and hybridized to oligonucleotide arrays. Resulting data were analyzed by bioinformatic approaches and revealed that 650 genes were significantly downregulated and 683 genes were significantly upregulated in the luteal vs. follicular phase. Real-time RT-PCR, immunoblot analysis, and immunohistochemistry confirmed select gene expression and cellular protein localization. The data demonstrate downregulation of genes involved in macrophage recruitment, immunomodulation, and matrix-degeneration and upregulation of ion transport and secretions as well as anti-angiogenic and early pregnancy recognition genes in luteal vs. follicular phase oviduct. Together, these data suggest a unique hormonally regulated environment during embryo development, maturation and transport through human oviduct.
The human oviduct transcriptome reveals an anti-inflammatory, anti-angiogenic, secretory and matrix-stable environment during embryo transit.
Specimen part
View SamplesWe used global gene expression profiles from human B-cell cell lines to generate gene expression signatures for prediction of response to the drugs cyclophosphamide, doxorubicin or vincristine. The signatures were validated in two publicly available clinical cohorts.
Predicting response to multidrug regimens in cancer patients using cell line experiments and regularised regression models.
Disease, Cell line
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A model system for assessing and comparing the ability of exon microarray and tag sequencing to detect genes specific for malignant B-cells.
Cell line
View SamplesDuring the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting immuno-acceptance of the fetal allograph. Global cross-talk between the trophoblast and the decidua has not been elucidated to date, and the current study used a functional genomics approach to investigate these paracrine interactions.
Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators.
No sample metadata fields
View SamplesThe purpose of this study was to develop a quantification method that can be used to assess the ability of tag-seq to detect malignant B-cell transcripts. The data support that tumour cell concentration is an important variable with fundamental impact on gene expression pattern. Overall design: We analysed eight serial dilutions of the malignant B-cell line, OCI-Ly8, into the embryonic kidney cell line, HEK293, by tag-sequencing. No technical replicates were performed.
A model system for assessing and comparing the ability of exon microarray and tag sequencing to detect genes specific for malignant B-cells.
Cell line, Subject
View SamplesThe purpose of this study was to develop a quantification method that can be used to assess the ability of exon microarray to detect malignant B-cell transcripts.
A model system for assessing and comparing the ability of exon microarray and tag sequencing to detect genes specific for malignant B-cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular classification of tissue from a transformed non-Hogkin's lymphoma case with unexpected long-time remission.
Sex, Specimen part
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