Project description:To investigate the responses of resistance gene Pi54 at transcriptome level in blast resistant transgenic rice line TP-Pi54 during infection by Magnaporthe oryzae, we studied the co-expression analysis using microarray along with susceptible non-transgenic line Taipei 309 (TP). Suitable controls for both lines were used. The comparative analysis of differentially expressed genes was conducted. Total RNA from the leaves of mock inoculated non transgenic line Taipei 309 (TP) and transgenic line (TP-Pi54) along with challenge inoculated plants were isolated at 72 hours post inoculation. The samples were analyzed in two different biological replications (A and B) making total eight samples.
Project description:To investigate the responses of resistance gene Pi54 at transcriptome level in blast resistant transgenic rice line TP-Pi54 during infection by Magnaporthe oryzae, we studied the co-expression analysis using microarray along with susceptible non-transgenic line Taipei 309 (TP). Suitable controls for both lines were used. The comparative analysis of differentially expressed genes was conducted.
Project description:To mimic the initial phases of systemic Candida infections with dissemination via the bloodstream, we used an ex vivo whole blood infection model. Dual TP of C. auris in blood gave insights into fungal adaptations and survival mechanisms as well as the host response to the infection.
Project description:Purpose: Compare transcriptional changes between drug treated (gilteritinib, TP-0903) and vehicle in acute myeloid leukemia xenografts. Methods: FLT3-ITD+ MOLM13-Luc+ AML cells were xenografted into NSG mice. Mice were randomized according to bioluminescence imaging, and treatment of FLT3 tyrosine kinase inhibitors (TP-0903, 60 mg/kg, once daily for 5 days/week; gilteritinib, 30 mg/kg, once daily for 5 days/week) was started on day 7 post-tail vein injection. At study end point, mice were humanely euthanized and bone marrow was collected. AML cells (human CD45+) were isolated, and RNA-seq was performed on total RNA. Sequencing reads were aligned and analyzed for differential gene expression of treatment vs vehicle cohorts. Results: The analysis revealed the transcriptional changes induced by TP-0903 or gilteritinib in MOLM13 AML xenograft model.
Project description:The thromboxane A2/prostaglandin H2 receptor (TP) plays an eminent role in the pathogenesis of cardiovascular disease and its expression has been reported to increase in the dysfunctional endothelium of cardiovascular high-risk patients. Yet it remains enigmatic in which way the vascular endothelial TP affects angiogenesis. Here we show that increased endothelial TP expression, in the absence of exogenous TP agonists, profoundly inhibits, whereas TP knockdown or endothelial-specific knockout enhance the angiogenic capacity of vascular endothelial cells in vitro and in vivo. Global transcriptome, lipidomic, and functional analyses reveal that the TP induces endothelial cyclooxygenase-2 and downregulates prostacyclin synthase to promote TP ligand release, persistent TP activation, suppression of VEGFR2 expression and inhibition of angiogenesis, effects that are reversed by pharmacological TP inhibition or prostacyclin synthase reconstitution. Further mechanistic analyses reveal that endothelial TP increase cell tension, disturb focal adhesion dynamics and inhibit migration, tube formation and angiogenic sprouting via pathways that enhance endothelial actomyosin contractility. In conclusion, our work uncovers an anti-angiogenic feedback loop by which the TP may disturb angiogenesis and vascular endothelial homeostasis in disease states associated with increased TP expression.
Project description:Piericidin A (PA), the most common member of the family of piericidins, is fermented from Streptomyces#sp.HBERC#58855. We have found that PA had significant cytostatic activity against the ACHN cells, which can be used as a potential drug against renal cell carcinoma (RCC). Therefore, we used the second-generation transcriptome sequencing (RNA-seq) to determine the expression changes of various genes in ACHN cells treated with PA (25nM,50nM) or DMSO (0.1%), so that we can investigate the molecular mechanism of PA against the RCC.
Project description:Thymidine phosphorylase (TP) catalyzes the reversible phosphorolysis of thymidine, deoxyuridine, and their analogs to the respective bases and 2-deoxy-D-ribose-1-phosphate. TP is identical to platelet-derived endothelial cell growth factor (PD-ECGF). TP was reported to induce many angiogenic factors. However, the molecular mechanism of the TP function is still obscure. To elucidate the molecular basis for the TP function in human epidermoid carcinoma KB cells, we performed a whole genome-wide microarray analysis. Genes upregulated in KB cells overexpressing TP are supposed to represent potential molecular targets of TP in KB cells.
Project description:A subset of post-infection irritable bowel syndrome (PI-IBS) patients have elevated, or high fecal proteolytic activity (PA). Fecal PA has been shown to correlate with increased symptom severity as well as lower quality of life scores, increased fecal output and increased intestinal permeability. To address the underlying mechanisms of barrier disruption as a consequence of high fecal PA, colonic biopsies were collected from healthy individuals PI-IBS patients (n=11). Individuals diagnosed with PI-IBS were further divided in to 2 subgroups, high PA and low PA as defined by the PA in matched fecal samples. RNA was extracted from the biopsies for bulk RNA sequencing to understand transcriptional differences between healthy and high PA PI-IBS patients as well as high PA and Low PA PI-IBS patients.
Project description:<p>The major goal of this project is to apply second generation resequencing technology to identify disease causing variants influencing pediatric and adult lung diseases in a collection of two longitudinal population cohorts of cystic fibrosis patients that have been well characterized for a comprehensive set of clinical traits. In Phase I, exome sequencing was performed on 43 cystic fibrosis patients with early <i>Pa</i> infection and 48 cystic fibrosis patients with late <i>Pa</i> infection to identify variants influencing the time to onset of <i>Pa</i> infection. In Phase II, additional exomes were added to the study, to reach a total of 91 individuals with early <i>Pa</i> infection and 96 with late <i>Pa</i> infection. The majority of the 340 subjects of Phase II do not have a <i>Pa</i> infection phenotype, but instead have a pulmonary function phenotype (121 severe vs. 124 mild impairment) as determined by the survival corrected Kulich FEV percentile of Corey et al. A small minority have intermediate phenotypes and/or show severe decline in lung function during childhood.</p>