Efferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Specimen part
View SamplesCarbon nanotubes are cylindrically-shaped carbon nanostructures, made up of layers of graphene rolled onto themselves, with diameters similar to those of neuronal processes. In the last decade, CNT have been used as biocompatible growing substrates for neuronal attachment, differentiation and growth. In the perspective of new developments in tissue engineering, and in particular in spinal cord repair strategies, based on the use of CNTs, our aim is to clarify the biophysical interactions between CNTs and spinal cord neurons, studying the development of the morphological and functional characteristics of spinal neurons grown on CNT-based interfaces.
Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.
Specimen part
View SamplesAldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear.
Effect of acute aldosterone administration on gene expression profile in the heart.
No sample metadata fields
View SamplesFlowering time is a complex trait regulated by many genes that are integrated in different genetic pathways. Different genetic screenings carried out during the past decades have revealed an intrincated genetic regulatory network governing this trait. Efforts aimed at improving our understanding of how such genetic pathways respond to genetic and enviromental cues are needed.
The arabidopsis DNA polymerase δ has a role in the deposition of transcriptionally active epigenetic marks, development and flowering.
Age, Specimen part
View SamplesOvercoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-Ras-V12-induced senescence. Mechanistically, a PAK4 – RELB - C/EBPa axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Se151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPa. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition. Overall design: We quantify transcription via high-throughput RNA sequencing in two human breast cancer cell lines (BT-549 and Hs578T) 72hrs after transient transfection with control (siControl) or PAK4-targetting siRNA.
PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer.
Specimen part, Cell line, Subject
View SamplesTo provide a global study of transcriptome changes under drought stress, the gene expression levels of a durum wheat genotype (Triticum durum Desf. cultivar Creso) and two bread wheat genotypes (Triticum aestivum L. cultivar Chinese Spring -CS- and its deletion line CS_5AL-10) were investigated. The 5A chromosome deletion line (5AL-10) lacks the distal part (43%) of the long arm of chromosome 5A. Each genotype was subjected to two different levels of water stress at the grain filling stage. After anthesis, three different levels of soil water content (SWC) were induced as described below: control (CTRL; SWC=28%), moderate stress (MS; SWC=18%), and severe stress (SS; SWC=12.5%). For each sample, three biological replicates were performed, for a total of 27 hybridizations. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Alessio Aprile. The equivalent experiment is TA23 at PLEXdb.]
Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome.
Specimen part, Treatment
View SamplesMetastasis leads to the majority of deaths in breast cancer patients. Here we investigated the molecular and biochemical signaling pathways altered by RECK, a major metastasis suppressor gene in breast cancer. We overexpressed RECK in 2 highly invasive cell lines and knocked-down RECK expression in 2 poorly invasive cell lines. IPA analysis of differentially expressed genes revealed IL-6, and IL8 signaling alteration with RECK pertubation. This lead us to discover that RECK suppresses metastasis and neoangiogenesis at secondary sites by inhibiting STAT3 dependent VEGF & uPA regulating. This finding is significant because it reveals the biology behind a major metastasis suppressor gene in cancer.
RECK controls breast cancer metastasis by modulating a convergent, STAT3-dependent neoangiogenic switch.
Specimen part, Cell line
View SamplesMost hepatocellular carcinomas in younger patients from Peru arise from non-cirrhotic livers. Histological examination of the non-tumor liver tissues highlights the presence of clear cell foci in a significant fraction of Peruvian patients with hepatocellular carcinoma.
Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America.
Specimen part, Disease stage, Subject
View SamplesGlioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression.
Transcriptional diversity of long-term glioblastoma survivors.
Disease stage
View SamplesHyperglycemia can contribute to the detrimental effects of diabetes in the vasculature.
Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization.
Specimen part
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