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listelement.badge.dso-type Item , Some aspects on PI-theory: bounded colength, minimal varieties and exponential growth(Universidade Federal de Minas Gerais, 2025-09-26) Wesley Quaresma CotaEsta tese situa-se no área das álgebras com identidades polinomiais, com foco principal na investigação do comportamento assintótico das identidades polinomiais e dos polinômios centrais em álgebras G-graduadas e em álgebras com involução graduada. Como determinar o conjunto completo de identidades polinomiais satisfeitas por uma dada álgebra é um problema notoriamente difícil, a teoria desenvolvida por Regev e Kemer desempenhou um papel crucial no avanço da área, ao propor uma abordagem baseada em invariantes numéricos associados à álgebra, tais como a sequência de codimensões, a sequência de cocomprimentos e o expoente. Esses invariantes, que constituem os objetos centrais deste trabalho, tornaram-se ferramentas essenciais no estudo de identidades polinomiais, fornecendo informações valiosas sobre seu crescimento assintótico. Esta dissertação concentra-se, em particular, em abordar três problemas fundamentais: (1) a classificação de variedades minimais de crescimento quadrático; (2) a classificação de variedades com cocomprimento limitado; e (3) a existência e integralidade do expoente central e do expoente central próprio. Os resultados obtidos contribuem significativamente para a classificação de variedades com crescimento polinomial e oferecem uma compreensão mais profunda do comportamento assintótico dos polinômios centrais em álgebras munidas de estruturas adicionais.listelement.badge.dso-type Item , MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells(Universidade Federal de Minas Gerais, 2017) Carolina Lavini Ramos; Hernandez Moura Silva; Alessandra Soares Schanoski; Sandra Maria Monteiro; Ludmila Rodrigues Pinto Ferreira; Ana Paula Pacanaro; Samirah Gomes; Janaína Batista; Kellen Faé; Jorge Kalil; Verônica CoelhoThe mechanisms underlying mesenchymal stem cells’ (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73+Foxp3+Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.listelement.badge.dso-type Item , Whole-Genome Cardiac DNA Methylation Fingerprint and Gene Expression Analysis Provide New Insights in the Pathogenesis of Chronic Chagas Disease Cardiomyopathy(Universidade Federal de Minas Gerais, 2017) Laurie Laugier; Amanda Farage Frade; Frederico Moraes Ferreira; Monique Andrade Baron; Priscila Camillo Teixeira; Sandrine Cabantous; Ludmila Rodrigues Pinto Ferreira; Laurence Louis; Vagner Oliveira Carvalho Rigaud; Fabio Antônio Gaiotto; Fernando Bacal; Pablo Pomerantzeff; Edimar Bocchi; Jorge Kalil; Ronaldo Honorato Barros Santos; Edecio Cunha Neto; Christophe ChevillardBackground: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects 10 million people worldwide. Approximately 12000 deaths attributable to Chagas disease occur annually due to chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy presenting with heart failure and arrythmia; 30% of infected subjects develop CCC years after infection. Genetic mechanisms play a role in differential progression to CCC, but little is known about the role of epigenetic modifications in pathological gene expression patterns in CCC patients’ myocardium. DNA methylation is the most common modification in the mammalian genome. Methods: We investigated the impact of genome-wide cardiac DNA methylation on global gene expression in myocardial samples from end-stage CCC patients, compared to control samples from organ donors. Results: In total, 4720 genes were differentially methylated between CCC patients and controls, of which 399 were also differentially expressed. Several of them were related to heart function or to the immune response and had methylation sites in their promoter region. Reporter gene and in silico transcription factor binding analyses indicated promoter methylation modified expression of key genes. Among those, we found potassium channel genes KCNA4 and KCNIP4, involved in electrical conduction and arrythmia, SMOC2, involved in matrix remodeling, as well as enkephalin and RUNX3, potentially involved in the increased T-helper 1 cytokine-mediated inflammatory damage in heart. Conclusions: Results support that DNA methylation plays a role in the regulation of expression of pathogenically relevant genes in CCC myocardium, and identify novel potential disease pathways and therapeutic targets in CCC.listelement.badge.dso-type Item , Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection(Universidade Federal de Minas Gerais, 2017) Ludmila Rodrigues Pinto Ferreira; Frederico Moraes Ferreira; Laurie Laugier; Sandrine Cabantous; Isabela Cunha Navarro; Darlan da Silva Cândido; Vagner Carvalho Rigaud; Juliana Monte Real; Glaucia Vilar Pereira; Isabela Resende Pereira; Leonardo Ruivo; Ramendra Pati Pandey; Marilda Savoia; Jorge Kalil; Joseli Lannes Vieira; Helder Nakaya; Christophe Chevillard; Edecio Cunha-NetoChagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions. Mouse models of T. cruzi infection have been used to study heart damage in Chagas disease. The aim of this study was to provide an interactome between miRNAs and their targetome in Chagas heart disease by integrating gene and microRNA expression profiling data from hearts of T. cruzi infected mice. Gene expression profiling revealed enrichment in biological processes and pathways associated with immune response and metabolism. Pathways, functional and upstream regulator analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs revealed enrichment in biological processes and pathways such as IFNγ, TNFα, NF-kB signaling signatures, CTL-mediated apoptosis, mitochondrial dysfunction, and Nrf2-modulated antioxidative responses. We also observed enrichment in other key heart disease-related processes like myocarditis, fibrosis, hypertrophy and arrhythmia. Our correlation study suggests that miRNAs may be implicated in the pathophysiological processes taking place the hearts of acutely T. cruzi-infected mice.listelement.badge.dso-type Item , Neuronal Parasitism, Early Myenteric Neurons Depopulation and Continuous Axonal Networking Damage as Underlying Mechanisms of the Experimental Intestinal Chagas' Disease(Universidade Federal de Minas Gerais, 2020) Mayra Fernanda Ricci; Samantha Ribeiro Béla; Michele Macedo Moraes; Maria Terezinha Bahia; Ana Lia Mazzet; Anny Carolline Silva Oliveira; Luciana Oliveira Andrade; Rafael Radi; Lucía Piacenza; Rosa Maria Esteves ArantesThere is a growing consensus that the balance between the persistence of infection and the host immune response is crucial for chronification of Chagas heart disease. Extrapolation for chagasic megacolon is hampered because research in humans and animal models that reproduce intestinal pathology is lacking. The parasite-host relationship and its consequence to the disease are not well-known. Our model describes the temporal changes in the mice intestine wall throughout the infection, parasitism, and the development of megacolon. It also presents the consequence of the infection of primary myenteric neurons in culture with Trypanosoma cruzi (T. cruzi). Oxidative neuronal damage, involving reactive nitrogen species induced by parasite infection and cytokine production, results in the denervation of the myenteric ganglia in the acute phase. The long-term inflammation induced by the parasite's DNA causes intramuscular axonal damage, smooth muscle hypertrophy, and inconsistent innervation, affecting contractility. Acute phase neuronal loss may be irreversible. However, the dynamics of the damages revealed herein indicate that neuroprotection interventions in acute and chronic phases may help to eradicate the parasite and control the inflammatory-induced increase of the intestinal wall thickness and axonal loss. Our model is a powerful approach to integrate the acute and chronic events triggered by T. cruzi, leading to megacolon.