Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.
Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury.
Specimen part
View SamplesWe aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis.
Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesTo understand the fruit changes and mechanisms involved in the compatible grapevine-virus interaction, we analyzed the berry transcriptome in two stages of development (veraison and ripening) in the red wine cultivar Cabernet Sauvignon infected with Grapevine leaf-roll-associated virus-3 (GLRaV-3). Analysis of global gene expression patterns indicate incomplete berry maturation in infected berries as compared to uninfected fruit suggesting viral infection interrupts the normal berry maturation process.
Compatible GLRaV-3 viral infections affect berry ripening decreasing sugar accumulation and anthocyanin biosynthesis in Vitis vinifera.
Age, Specimen part
View SamplesPlant growth promoting rhizobacteria (PGPR) induce positive effects in plants, such as increased growth or reduced stress susceptibility. The mechanisms behind PGPR/plant interaction are poorly understood, as most studies have described short- term responses on plants and only a few studies have analyzed plant molecular responses under PGPR colonization.
Effects of the plant growth-promoting bacterium Burkholderia phytofirmans PsJN throughout the life cycle of Arabidopsis thaliana.
Specimen part, Time
View SamplesBoron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We used microarrays to detail the global gene expression underlying boron toxicity in roots.
A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.
Specimen part, Treatment
View SamplesMammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a low/low/high/low or LLHL, which allowed the identification of genes regulated by mTORC1 by performing the appropriate comparisons
Regulation of TFEB and V-ATPases by mTORC1.
Specimen part, Treatment
View SamplesHistone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (E). Here, we report that the E-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of E-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Specimen part
View SamplesThe beneficial effect of the selective
Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome.
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View SamplesRNA from wt and SIN1 knock-out MEF cell lines were compared
mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1.
Specimen part
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