Immunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND. METHODS: mRNA was isolated from the monocytes of 86 HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined.
Transcriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning.
Age, Specimen part, Disease, Disease stage, Race
View SamplesMammalian lung development is a complex morphogenetic process, which initiates near mid-gestation and continues through early postnatal life. The lung arises as two lateral buds that emerge from the ventral foregut endoderm at ~ 9 days after fertilization (in mouse) and undergo numerous rounds of dichotomous branching to form the bronchial tree. This stage of development is referred to as the pseudoglandular phase, histologically characterized by loose mesenchyme surrounding undifferentiated epithelial tubes.
Expression profiling of the developing mouse lung: insights into the establishment of the extracellular matrix.
No sample metadata fields
View SamplesP. falciparum NF54 proliferates under micro-aerophilic conditions in an environment of 3% O2, 4% CO2, 93% N2. This strain was gradually adapted to proliferate under standard tissue culture conditions of 5% CO2/95% air (~19% O2) to generate P. falciparum HOX. We compared global gene expression profiles of the two strains to identify differences, if any.
Model system to define pharmacokinetic requirements for antimalarial drug efficacy.
No sample metadata fields
View SamplesCDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-ß pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday. Overall design: To analyse the binding targets of miR-432-5p we performed a mRNA pulldown using a synthetic biotin laballed miR-432-5p. RNAseq was performed to identify the captured mRNA.
MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance.
Specimen part, Subject
View SamplesRNA sequencing of nucleus pulposus cells transduced with shRNA (control or TonEBP-targeted) and either untreated or treated with TNF-a (24h) Overall design: Total mRNA was collected from primary nucleus pulposus cells and subjected to RNA sequencing, n=3 for all experimental groups
TNF-α promotes nuclear enrichment of the transcription factor TonEBP/NFAT5 to selectively control inflammatory but not osmoregulatory responses in nucleus pulposus cells.
No sample metadata fields
View SamplesWe analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Time
View SamplesThis study examines the innate immune response of human pluripotent stem cell derived airway epithelium. Immune challenge was performed with TNF-alpha or bacterial lipopolysaccharide (LPS)
Innate immune response of human pluripotent stem cell-derived airway epithelium.
Specimen part, Treatment
View SamplesThe retinoblastoma tumor suppressor protein (Rb) regulates early G1 phase checkpoints, including the DNA damage response, as well as cell cycle exit and differentiation. The widely accepted model of G1 cell cycle progression proposes that cyclin D:Cdk4/6 partially inactivates the Rb tumor suppressor during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, resulting in release of E2F transcription factors. However, this model remains largely unproven biochemically and the biologically active form(s) of Rb remains unknown. Here we find that Rb is un-phosphorylated in G0 cells and becomes exclusively mono-phosphorylated throughout all of early G1 phase by cyclin D:Cdk4/6. Early G1 phase mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but each shows a preferential binding pattern to specific E2F1-4 transcription factors. At the late G1 Restriction Point, cyclin E:Cdk2 inactivates Rb by a quantum hyper-phosphorylation (>12 phosphates/Rb). Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription. In contrast, a non-phosphorylatable ?Cdk-Rb allele was non-functional for regulating a DNA damage response, but functional for driving cell cycle exit and differentiation during myogenesis. These observations fundamentally change our understanding of G1 cell cycle progression and show that there is no progressive multi-phosphorylation or hypo-phosphorylation inactivation of Rb during early G1 phase by cyclin D:Cdk4/6. Instead, cyclin D:Cdk4/6 generates functionally active, mono-phosphorylated Rb that is the only Rb isoform present in cells during early G1 phase.
Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.
Specimen part
View SamplesThe mammalian forebrain is a tissue of stunning complexity comprised of numerous regions each containing many distinct cell types that differ in their intrinsic and synaptic physiology, morphology and connectivity. These differences are likely conferred by differential gene expression, but the extent and nature of cell type specific gene expression is largely unknown. Here, we carried out microarray analysis of twelve major classes of fluorescently labelled neurons within the forebrain and provide the first comprehensive view of gene expression differences. The results demonstrate a profound molecular heterogeneity among neuronal subtypes, represented disproportionately by gene paralogs, and begin to reveal the genetic programs underlying the fundamental divisions between neuronal classes including that between glutamatergic and GABAergic neurons.
Molecular taxonomy of major neuronal classes in the adult mouse forebrain.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
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