We aimed to determine the infect of Ascaris suum infection on mucosal immune pathways in pigs
Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro.
Specimen part
View SamplesUncontrolled microglial activation may lead to development of inflammation-induced brain damage. Here we uncover a ribosome-based mechanism/check point involved in control of the innate immune response and microglial activation. Using an in vivo model-system for analysis of the dynamic translational state of microglial ribosomes with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly up-regulated and ribosome-associated mRNAs were not translated resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA and immunomodulatory/homeostatic protein signature. We find that this is due to specific translational suppression of highly expressed mRNAs through a 3UTR-mediated mechanism involving the RNA binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia.
Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts.
Treatment
View SamplesCell-type specific transcriptional profiles were generated by FACS (Fluorescence Activated Cell Sorting) sorting of roots that express cell-type specific GFP-reporters. Four different GFP-reporter lines were utilized allowing us to obtain transcriptional profiles for cells in major radial zones of the root. FACS cell populations were isolated from roots grown under standard conditions or roots that had been transfered to media supplemented with 140 mM NaCl for 1 hour, 3 hours, 8 hours, 20 hours, 32 hours and 48 hours.
A spatio-temporal understanding of growth regulation during the salt stress response in Arabidopsis.
Specimen part
View SamplesThe purpose of this study was to analyze the transcriptional effects induced by glatiramer acetate treatment (GA; Copaxone, 20 mg injected subcutaneously once daily) in blood monocytes of patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of monocytes from 8 MS patients within the first two months of GA administration.
Glatiramer acetate treatment effects on gene expression in monocytes of multiple sclerosis patients.
Sex, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients.
Sex, Disease
View SamplesThe purpose of this study was to investigate the expression dynamics of mRNAs and microRNAs in response to subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) or relapsing-remitting type of the disease (RRMS).
MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients.
Sex, Disease
View SamplesWe present single-cell mRNA-Sequencing of various endothelial and hematopoietic populations isolated from the mouse embryonic aorta at E10 and E11. Our study reveals the transcriptional dynamics occuring during endothelial to hematopoietic transition, the process responsible for the production of hematopoietic stem cells. Overall design: single-cell mRNA-Sequencing of various endothelial and hematopoietic populations isolated from the mouse embryonic aorta at E10 and E11
Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta.
Specimen part, Cell line, Subject
View SamplesGene silencing via heterochromatin formation plays a major role in cell differentiation and maintenance of homeostasis. Here, we report the identification and characterization of a novel heterochromatinization factor in vertebrates, Bromo Adjacent Homology Domain-containing protein 1 (BAHD1). BAHD1 interacts with HP1, MBD1, HDAC5 and with several transcription factors. Through electron and immunofluorescence microscopy studies, we show that BAHD1 overexpression directs HP1 to specific nuclear sites and promotes formation of large heterochromatic domains, which lack acetyl histone H3 and are enriched in H3 trimethylated at lysine 27. Furthermore, ectopically expressed BAHD1 colocalizes with the heterochromatic X inactive chromosome. As highlighted by whole genome microarray analysis of BAHD1 knock down cells, BAHD1 represses several proliferation and survival genes and in particular, the insulin-like growth factor II gene (IGF2). BAHD1 specifically binds the CpG-rich P3 promoter of IGF2. This region contains DNA binding sequences for the transcription factor SP1, with which BAHD1 co-immunoprecipitates. Collectively, these findings provide evidence that BAHD1 acts as a silencer by recruiting proteins that coordinate heterochromatin assembly at specific sites in the genome.
Human BAHD1 promotes heterochromatic gene silencing.
Cell line
View SamplesEndocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
A phase II neoadjuvant trial of anastrozole, fulvestrant, and gefitinib in patients with newly diagnosed estrogen receptor positive breast cancer.
No sample metadata fields
View SamplesAlthough many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neural degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered sub-cellular transport as well as activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that perturbations in these pathways were indeed the source of altered transcript levels. Overall design: 5 samples, 2 patient-derived SOD1A4V and 3 isogenic control samples where the mutation has been corrected. All samples are motor neurons derived from induced pluripotent stem cells (iPSCs), and isolated after lentiviral infection with an Hb9:RFP construct and FACS purification. Each sample is a separate biological replicate.
Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1.
No sample metadata fields
View Samples