Project description:Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
Project description:Burkholderia oklahomensis EO147 agglutinin (BOA) is a 29 kDa member of the Oscillatoria agardhii agglutinin (OAA) family of lectins. Members of the OAA family recognize high-mannose glycans, and, by binding to the HIV envelope glycoprotein 120 (gp120), block the virus from binding to and entering the host cell, thereby inhibiting infection. OAA-family lectins comprise either one or two homologous domains, with a single domain possessing two glycan binding sites. We solved the structure of BOA in the ligand-free form as well as in complex with four molecules of 3?,6?-mannopentaose, the core unit of the N-linked high-mannose structures found on gp120 in vivo. This is the first structure of a double-domain OAA-family lectin in which all four binding sites are occupied by ligand. The structural details of the BOA-glycan interactions presented here, together with determination of affinity constants and HIV inactivation data, shed further light onto the structure-function relationship in this important class of anti-HIV proteins.
Project description:Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
Project description:Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld–Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 (IRF1) and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer.
Project description:Marjolin’s Ulcer is an aggressive cutaneous malignancy that typically ensues over a period of time in the post-burned lesions and scars or any other chronic wound. Marjolin’s Ulcer makes up 1.2% of all skin cancers, it is reported that 2% of squamous cell carcinoma and 0.03% of basal cell carcinoma originate in burn scars. Recent studies have shown that long non-coding (lncRNA) plays critical roles in a myriad of biological processes and human diseases,Since the roles of lncRNA in Marjolin’s Ulcer remain unknown,they were investigated in the study.Our findings indicate that the expression profiles of lncRNAs has changed in Marjolin’s Ulcer as compared with normal skin and para-cancerous scar, and may provide novel insight into the molecular mechanism underlying the disease and potential novel diagnostic or therapeutic targets for Marjolin’s Ulcer.