This article reports on the full genome sequence of Paenibacillus terrae HPL-003, which is a gram-positive, endospore-forming, xylanase-producing bacterium isolated from soil found in forest residue on Gara Mountain. The strain HPL-003 contains 6,083,395 bp with a G+C content of 46.77 mol%, 2,633 protein-coding genes, and 117 structural RNAs. ...[more]
Project description:MORAB-003 significantly upregulated a number of genes involved in autophagic processing, including GABARAPL2, LC3II (MAP1LC3B), ATG3, ATG4B, and BECN1, while expression of the oncogenic factor PIK3C3 was downregulated. We used microarrays to detail the global programme of gene expression underlying growth inhibition of ovarian cancer cells treated with MORAB-003 microarray analysis of SKOV3ip1 cells with and without MORAb-003 treatment was performed under the following conditions: 1) cells plated in folate-free medium (7 days), 2) cells plated in medium with physiological levels of folic acid (2-10 nm) (7 days), 3) cells with physiological levels of folic acid (7 days) and 003 antibody (24 hours), 4) cells with physiologic levels of folic acid (7 days) and control 004 antibody (24 hours); 5) cells with physiological levels of folic acid (7 days) and MORAb003 antibody (24 hours) . For each condition, a single cell growth was carried out and an RNA sample was extracted. Three aliquots from each RNA sample were then hybridized to Affymetrix U133 2 arrays, for a total of 15 arrays. time course 7days and 24 hours
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy, with most patients facing an adverse clinical outcome. Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective γ-secretase inhibitor, in preclinical PDAC models. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity. In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity. Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice. In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts. Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFκB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. Pancreatic ductal adenocarcinoma xenografts were grown in Athymic Nude-Foxn1nu mice. RNA was extracted and profiled in Affymetrix platform to identify genes correlating with sensitivity to MRK-003
Project description:Transcriptional profiling of the bacteria Paenibacillus vortex comparing control untreated cells with kanamycin treated cells after 18 hours of exposure. Goal was to determine the effect of the antibiotic kanamycin in concentration which affect the colony morphology on global bacteria gene expression. Two-condition experiment, control cells vs. kanamycin treated cells. Biological replicates: 2 control replicates, 2 treated replicates. Pooling of 5 technical replicates for each biological replicate.
Project description:Fifty six genes from DESeq were differentially expressed in the treated versus control samples. More than 20% were related to immune, defense, wounding and inflammatory responses Overall design: Downregulation of REST-003 using siRNAs in MDA-MB-231 cells; we used siRNA against REST-003, as REST-003 may control invasiveness. We transfected si-Control (scramble) or si-REST-003 in MDA-MB-231: duplicate of both (total 4 samples).