Project description:Muscle wasting in Duchenne Muscular Dystrophy is caused by myofiber fragility and poor regeneration that leads to chronic inflammation and muscle replacement by fibrofatty tissue. Our recent findings demonstrated that Resolvins, a class bioactive lipids derived from omega-3 fatty acids, have the capacity to dampen inflammation and stimulate muscle regeneration to alleviate disease progression. This therapeutic avenue has many advantages compared to glucocorticoids, the current gold-standard treatment for Duchenne Muscular Dystrophy. However, the use of bioactive lipids as therapeutic drugs also faces many technical challenges such as their short-half life. Here, we explored the potential of synthetic agonist of bioactive lipid receptor, namely the Gpr18 agonist PSB-KD107, as a therapeutic alternative for Duchenne Muscular Dystrophy. We showed that PSB-KD107 can stimulate the myogenic capacity of human iPSC-derived myoblasts in vitro. RNAseq analysis revealed an enrichment in biological processes related to lipid metabolism, small molecule biosynthesis, and steroid-related processes in PSB-KD107-treated cells, as well as pathways related to fatty acid signaling such as Peroxisome proliferator-activated receptors, AMP-activated protein kinase, and sphingolipid signaling pathways. In vivo, the treatment of dystrophic mdx mice with PSB-KD107 resulted in reduced inflammation, enhanced myogenesis, and improved muscle function compared to vehicle-treated mice. Overall, our findings identified a novel therapeutic target for the treatment of Duchenne Muscular Dystrophy.
Project description:Genome-wide target genes of PPD2 were identified through ChIP-seq on Arabidopsis cell cultures. For ChIP-seq, PPD2 was fused to the GSyellow TAP tag and expressed from the 35S promoter. The p35S:PPD2-GSyellow construct was transformed into Arabidopsis thaliana PSB-D cell culture. ChIP was performed using anti-GFP antibody (abcam290).
Project description:RNA was isolated from wild-type dark grown PSB-D cell cultures in three biological repeats using the RNeasy Plant Mini Kit (Qiagen) and DNase I treated (Promega). A Trueseq RNA-Seq library (Illumina) was compiled and sequenced as 50-bp single read using Illumina HiSeq 2000.
Project description:Phosphate-solubilizing bacteria (PSB) have the ability to dissolve insoluble phosphate and enhance soil fertility. However, the growth and mineral phosphate solubilization of PSB could be affected by exogenous soluble phosphate and the mechanism has not been fully understood. In the present study, the growth and mineral phosphate-solubilizing characteristics of PSB strain Burkholderia multivorans WS-FJ9 were investigated at six levels of exogenous soluble phosphate (0, 0.5, 1, 5, 10 and 20 mM). The WS-FJ9 strain showed better growth at high levels of soluble phosphate. The phosphate-solubilizing activity of WS-FJ9 reduced as the soluble phosphate concentration increased, as well as the production of pyruvic acid. Transcriptome profiling of WS-FJ9 at three levels of exogenous soluble phosphate (0, 5 and 20 mM) identified 446 differentially expressed genes, among which 44 genes were continuously up-regulated when soluble phosphate concentration increased and 81 genes were continuously down-regulated. Some genes related to cell growth were continuously up-regulated which would account for the better growth of WS-FJ9 at high levels of soluble phosphate. Genes involved in glucose metabolism, including glycerate kinase, 2-oxoglutarate dehydrogenase, and sugar ABC-type transporter were continuously down-regulated which indicates that metabolic channeling of glucose towards phosphorylative pathway was negatively regulated by soluble phosphate.
Project description:Xanthomonas oryzae pv. oryzae strain PXO99A, so called Xoo, is disable to infect in rice cultivar carrying Xa21 gene. Disrupted mutant of raxR gene, response regulator of two-component regulatory system (TCS), in Xoo was previously shown to partially retrieve back the bacterial capability to establish in Xa21 rice. RaxR was shown to mediate the expression of other rax gene operon members and also its expression is changed dependent on cell population density. In this study, we investigated the regulatory mechanisms mediated by RaxR using whole-genome transcriptional profiling analysis in comparison of (i) PXO99R (PXO99 strain lacking RaxR) vs. PXO99, (ii) PXO99Rox (PXO99 strain overexpressing RaxR) vs. PXO99, and (iii) PXO99Rox vs. PXO99R. As a result of array analysis, we revealed that RaxR is not only required for AvrXa21 activitiy, it also plays roles in regulatory functions, for example, pathogenicity, motility, and stress tolerance. Then, we generated knock out mutants of RaxR regulon members to validate regulatory functions of RaxR and to extend other biological impacts of RaxR beyond the Xoo AvrXa21 activity. The combined interpretation from array analysis and mutant functional validation presents the complexity of regulatory pathways between AvrXa21 activity and other biological activities in Xoo. Keywords: Comparative transcription profiling between modified genetic mutant and wild type Three biological and dye-swap replicates, total six samples for each dataset. Three datasets contained; (i) raxR knockout mutant vs. wildtype PXO99A in PSB, nutrient rich media (ii) RaxR constitutively express mutant vs. wildtype PXO99A in PSB, nutrient rich media, and (iii) raxR knockout mutant vs. RaxR constitutively express mutant in PSB, nutrient rich media
Project description:Goal:identify the genes regulated by RON2 involved in the delay of floral transitional and those associated with leaf development. The gene expression profile of mature leaf 6 of ron2-1 EMS mutant and the wild-type Ler are compared. The plant material for this experiment was grown in LEPSE-INRA Montpellier, and the microarrays at the MAF-VIB Leuven with PSB-VIB Ghent.
Project description:Primary outcome(s): Overall survival Relationship between treatment outcomes of BRAF inhibitor combination therapy and genomic data on pretreatment ctDNA and RNA analysis