{"title":"Review of Set Theory","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1201/9780429464676-1","DOIUrl":"https://doi.org/10.1201/9780429464676-1","url":null,"abstract":"","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130718953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As circulating monocytes enter the site of disease, the local microenvironment instructs their differentiation into tissue macrophages (M Φ ). To identify mechanisms that regulate M Φ differentiation, we studied human leprosy as a model, since M1-type antimicrobial M Φ predominate in lesions in the self-limited form, whereas M2-type phagocytic M Φ are charac-teristic of the lesions in the progressive form. Using a heterotypic co-culture model, we found that unstimulated endothelial cells (EC) trigger monocytes to become M2 M Φ . How-ever, biochemical screens identified that IFN- γ and two families of small molecules activated EC to induce monocytes to differentiate into M1 M Φ . The gene expression profiles induced in these activated EC, when overlapped with the transcriptomes of human leprosy lesions, identified Jagged1 (JAG1) as a potential regulator of M Φ differentiation. JAG1 protein was preferentially expressed in the lesions from the self-limited form of leprosy, and localized to the vascular endothelium. The ability of activated EC to induce M1 M Φ was JAG1-dependent and the addition tuberculoid leprosy. These differences in the immune response can be characterized by the phenotype and activation state of the macrophage. We illustrate how the local endothelial microenvironment can “ educate ” macrophages, identifying Jagged1 and select small molecules that can regulate this pathway. Therefore, these studies identify a potential strategy to intervene in infection and inflammation, by targeting macrophage instruction at the site of disease. Through the integration of in vitro modeling and gene expression profiles at the site of disease, we found that Jagged 1 harnesses the endothelial microenvironment to instruct antimicrobial macrophage responses in leprosy.
当循环单核细胞进入疾病部位时，局部微环境指示它们分化为组织巨噬细胞(M Φ)。为了确定调节M Φ分化的机制，我们研究了人类麻风病作为模型，因为m1型抗菌M Φ在自限性病变中占主导地位，而m2型吞噬性M Φ是进行性病变的特征。使用异型共培养模型，我们发现未受刺激的内皮细胞(EC)触发单核细胞变成M2 M Φ。然而，生化筛选发现IFN- γ和两个小分子家族激活EC，诱导单核细胞分化为M1 - M Φ。在这些活化EC中诱导的基因表达谱，当与人类麻风病变的转录组重叠时，鉴定出Jagged1 (JAG1)是M Φ分化的潜在调节因子。JAG1蛋白在自限性麻风病变中优先表达，并定位于血管内皮。活化EC诱导M1 - M Φ的能力依赖于jag1和附加结核样麻风。这些免疫反应的差异可以通过巨噬细胞的表型和激活状态来表征。我们说明了局部内皮微环境如何“教育”巨噬细胞，识别Jagged1并选择可以调节这一途径的小分子。因此，这些研究确定了通过在疾病部位靶向巨噬细胞指令来干预感染和炎症的潜在策略。通过整合体外模型和疾病部位的基因表达谱，我们发现Jagged 1利用内皮微环境指导麻风病中的抗菌巨噬细胞反应。
{"title":"Differentiation","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1201/9780429464676-7","DOIUrl":"https://doi.org/10.1201/9780429464676-7","url":null,"abstract":"As circulating monocytes enter the site of disease, the local microenvironment instructs their differentiation into tissue macrophages (M Φ ). To identify mechanisms that regulate M Φ differentiation, we studied human leprosy as a model, since M1-type antimicrobial M Φ predominate in lesions in the self-limited form, whereas M2-type phagocytic M Φ are charac-teristic of the lesions in the progressive form. Using a heterotypic co-culture model, we found that unstimulated endothelial cells (EC) trigger monocytes to become M2 M Φ . How-ever, biochemical screens identified that IFN- γ and two families of small molecules activated EC to induce monocytes to differentiate into M1 M Φ . The gene expression profiles induced in these activated EC, when overlapped with the transcriptomes of human leprosy lesions, identified Jagged1 (JAG1) as a potential regulator of M Φ differentiation. JAG1 protein was preferentially expressed in the lesions from the self-limited form of leprosy, and localized to the vascular endothelium. The ability of activated EC to induce M1 M Φ was JAG1-dependent and the addition tuberculoid leprosy. These differences in the immune response can be characterized by the phenotype and activation state of the macrophage. We illustrate how the local endothelial microenvironment can “ educate ” macrophages, identifying Jagged1 and select small molecules that can regulate this pathway. Therefore, these studies identify a potential strategy to intervene in infection and inflammation, by targeting macrophage instruction at the site of disease. Through the integration of in vitro modeling and gene expression profiles at the site of disease, we found that Jagged 1 harnesses the endothelial microenvironment to instruct antimicrobial macrophage responses in leprosy.","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134349367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metric Spaces – Basic Concepts, Complete Metric Spaces","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1201/9780429464676-4","DOIUrl":"https://doi.org/10.1201/9780429464676-4","url":null,"abstract":"","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127919923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Connectedness and Compactness","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1007/0-387-22727-x_4","DOIUrl":"https://doi.org/10.1007/0-387-22727-x_4","url":null,"abstract":"","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114875563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sequences and Series of Real Numbers","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1201/9780429464676-3","DOIUrl":"https://doi.org/10.1201/9780429464676-3","url":null,"abstract":"","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123655601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integration","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1201/9780429464676-8","DOIUrl":"https://doi.org/10.1201/9780429464676-8","url":null,"abstract":"","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116090935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sequences and Series of Functions","authors":"H. Dutta, P. Natarajan, Y. Cho","doi":"10.1201/9780429464676-9","DOIUrl":"https://doi.org/10.1201/9780429464676-9","url":null,"abstract":"","PeriodicalId":202330,"journal":{"name":"Concise Introduction to Basic Real Analysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123469087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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