Este trabalho tem como objetivo e se justifica por analisar o primeiro movimento da Sinfonia n. 3, de Mahler (1860-1911) sob a ótica da vertente teórica que considera a forma como processo, no tempo. Composta em 1895, esta peça apresenta uma combinação de processos harmônicos dilatados pelo uso do cromatismo, entradas sucessivas de elementos temáticos, passagens direcionadas por eventos com flutuações na densidade, textura, timbre e rítmica, o que resultou em certa dissolução nas fronteiras formais tradicionais. Para atingir tal meta, tem por base os conceitos de forma como processo segundo Schmalfeldt (2011); música como processo por Hasty (1997); e breves considerações acerca de filosofia do processo e devir, de acordo com Seibt (2013). De maneira complementar às nossas discussões acerca de forma como processo, o \"modelo\" de Forma Sonata se fundamenta em Hepokosky e Darcy (2006) e as funções formais da sentença, em Caplin (1998). Os gráficos de vozes condutoras schenkerianas são apresentados segundo Forte e Gilbert (1992), e Neumeyer e Tepping (1992); os cinco componentes da tonalidade, de acordo com Tymoczko (2011); aspectos de textura, rítmica e dinâmica têm por base as considerações apresentadas por Berry (1987), Erickson (1975), Kostka (2012) e Schoenberg (2008 [1967]); aspectos de cunho histórico se baseiam principalmente em Fischer (2011) e Liberman (2010). Na conclusão buscamos a inter-relação das questões históricas e as da análise musical, resgatando os principais aspectos de nossa análise processualmente baseada sob a luz de uma reflexão sobre as questões revelados. / This work aims to analyze the first movement of Mahler\'s 3rd Symphony from the perspective of Form as Process. Composed in 1895, this musical piece features a combination of expanded harmonic processes by use of chromaticism, thematic elements, and events with fluctuations in density, texture, timbre and rhythm, which results in some dissolution from formal boundaries. To achieve this goal, we have based on the concepts of Form as Process, according to Schmalfeldt (2011); Music as Process, according to Hasty (1997); and Process Philosophy and Becoming, according to Seibt (2013). Complementary to these ideas we present Sonata Form according to Hepokosky and Darcy (2006) and Sentence according to Caplin (1998). We also present concepts of these authors: Forte and Gilbert (1992) and Neumeyer and Tepping (1992), schenkerian analysis; Tymoczko (2011), Five Components of Tonality; Berry (1987), Erickson (1975), Kostka (2012) and Schoenberg (2008 [1967]), liquidation, aspects of texture, rhythm and dynamic; Fischer (2011) and Liberman (2010), historical perspective. At the conclusion we present reflections about our musical analysis and relate it to historical issues.

Contexte. L'alimentation apporte à la fois des nutriments nécessaires au fonctionnement physiologique normal de l'organisme et des contaminants susceptibles d'impacter sur la santé. Il convient donc de prendre en compte ces deux aspects dans la détermination des consommations optimales du point de vue de la santé publique. Les produits de la mer représentent un cas d'étude intéressant car ils apportent à la fois des acides gras polyinsaturés oméga 3 à longue chaine (AGPI LC n-3), des vitamines et des oligoéléments, mais aussi du méthylmercure, de l'arsenic ou encore de polluants organiques persistants. Objectifs. L'objectif de la thèse était de déterminer dans quelles quantités la consommation de produits de la mer présentait un bénéfice nutritionnel, tout en limitant le risque lié aux contaminants apportés par l'alimentation. Méthodes. Les analyses ont principalement porté sur les données de l'étude Calipso menée sur 996 forts consommateurs de produits de la mer (au moins deux occurrences par semaine) de 18 ans et plus. Leurs apports nutritionnels et leur exposition aux contaminants ont été estimés à partir du recueil des consommations alimentaires et de biomarqueurs. Ce travail a permis, au regard de la couverture des besoins nutritionnels et des risques nutritionnels et sanitaire, la sélection de nutriments et contaminants pertinents, à l'apport desquels et à l'exposition auxquels les produits de la mer contribuent majoritairement. L'analyse risque-bénéfice a consisté en l'utilisation d'un modèle d'optimisation sous contraintes pour déterminer des consommations optimales de produits de la mer. L'objectif était d'optimiser les apports nutritionnels et l'exposition aux contaminants, sous contrainte d'atteinte des apports nutritionnels conseillés (ANC) et de non dépassement des valeurs toxicologiques de référence (VTR), en tenant compte des apports par le reste du régime. Résultats. Chez les forts consommateurs de produits de la mer, le risque sanitaire lié à l'exposition aux méthylmercure et l'arsenic inorganique ne sont pas négligeables. Chez ces mêmes consommateurs, les produits de la mer apparaissent également comme contributeurs majeurs d'apport en vitamine D et certains minéraux. Par ailleurs, une consommation de plus de 200 g/sem de poissons très gras n'entraine pas de bénéfice supplémentaire en termes de biomarqueur de santé cardiovasculaire. Tenant compte de ces éléments, il a été déterminé une consommation dite optimale, permettant à la fois de minimiser l'exposition à l'arsenic inorganique et d'augmenter l'apport de vitamine D en population générale, tout en garantissant l'atteinte de l'ANC pour les AGPI LC n-3, le sélénium et l'iode, le non dépassement des VTR établies pour le méthylmercure, le cadmium, les dioxines et polychlorobiphényles, ainsi que le non dépassement des limites de sécurité établies pour le zinc, le calcium et le cuivre. Cette consommation est de 200 g/semaine environ de certaines espèces de poissons gras et de 50 g/semaine environ de poissons maigres, mollusques ou crustacés. Conclusion. Une consommation optimale de produits de la mer entrainant à la fois un bénéfice nutritionnel et un risque sanitaire maitrisé a pu être définie. Il ressort de ce travail la nécessité de réduire les expositions à l'arsenic et d'affiner les résultats en utilisant le modèle pour certaines populations, en tenant compte des spécificités de ces populations.

<p>Insulin sensitivity is related to the fatty acid profile of skeletal muscle. The aim of this thesis was to investigate whether physical activity and dietary fat quality, independent of each other, influence the fatty acid composition of the skeletal muscle lipids. In an intervention study where middle-aged men were exercising for six weeks, and in a cross-sectional study comparing sedentary with endurance trained young men, it was demonstrated that the fatty acid composition of skeletal muscle lipids differed between physical active and inactive men. In brief, a lower proportion of palmitic acid (16:0) and total n-6 polyunsaturated fatty acids (PUFA) and a higher proportion of stearic (18:0) and oleic acid (18:1n-9) and total n-3 PUFA in the muscle phospholipids were associated with physical activity, despite similar fatty acid composition of the diet. In the second study, that included a larger training volume, differences in the fatty acid profile were also found in the skeletal muscle triglycerides. </p><p>In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle. </p><p>Furthermore, after a treatment period of three months, with diets with various dietary fat quality, the proportions of saturated fatty acids (14:0, 15:0 and 17:0) were higher and the proportion of 18:1 n-9 lower in subjects with a high intake of saturated fatty acids compared with subjects with a high intake of monounsaturated fatty acids. In addition subjects given n-3 supplementation had a higher proportion of total n-3 PUFA and lower n-6 PUFA in the skeletal muscle phospholipids than controls. Differences similar to those observed in the phospholipids were found in the triglycerides. </p><p>In summary, these results suggest that regular aerobic physical activity and dietary fat quality influence the fatty acid composition of the skeletal muscle lipids, which may affect insulin sensitivity and glucose homeostasis. </p>

<p>Numerous diseases are associated with reduced antioxidant defence and oxidative stress. The antioxidant defence includes dietary and endogenous antioxidants and involves complex interactions between them. The effects of dietary factors on antioxidant status and oxidative stress of healthy humans were investigated in the studies described in this thesis. Assays of plasma antioxidant capacity encompass interactions between various antioxidants. Although uric acid has an unclear function as an antioxidant, it is a major determinant of antioxidant capacity. We measured antioxidant capacity in the presence and absence of uric acid to provide more information on the application of measures of antioxidant capacity. Individuals with high dietary intakes of various antioxidants and antioxidant rich foods, especially when combined, had higher plasma antioxidant capacities than those with lower antioxidant intakes. However, there were no associations between dietary intake of antioxidants or antioxidant rich foods and the plasma concentration of F₂-isoprostanes, which is considered a reliable biomarker for oxidative stress. Intakes of various doses of a mixture of bilberry juice and black tea, rich in flavonoids for four weeks, increased antioxidant capacity in some groups, but urine levels of F₂-isoprostanes were not affected. There were substantial individual variations in responses to the drinks related to baseline antioxidant capacity. Supplementation with eicosapentaenoic acid and docosahexaenoic acid decreased the plasma levels of F₂-isoprostanes, but not prostaglandin F_2α formation or antioxidant capacity. </p><p>It was concluded that a high intake of foods rich in antioxidants is related to improved antioxidant status. After intake of foods rich in antioxidants, the antioxidant status may increase, but with considerable individual variation in the responses, which warrants further investigation. Lipid peroxidation <i>in vivo</i> is not easily affected by dietary antioxidants in healthy humans. Although n-3 fatty acids are highly unsaturated, they reduce nonenzymatic free radical-catalyzed lipid peroxidation, but not enzymatic lipid peroxidation.</p>

Insulin sensitivity is related to the fatty acid profile of skeletal muscle. The aim of this thesis was to investigate whether physical activity and dietary fat quality, independent of each other, influence the fatty acid composition of the skeletal muscle lipids. In an intervention study where middle-aged men were exercising for six weeks, and in a cross-sectional study comparing sedentary with endurance trained young men, it was demonstrated that the fatty acid composition of skeletal muscle lipids differed between physical active and inactive men. In brief, a lower proportion of palmitic acid (16:0) and total n-6 polyunsaturated fatty acids (PUFA) and a higher proportion of stearic (18:0) and oleic acid (18:1n-9) and total n-3 PUFA in the muscle phospholipids were associated with physical activity, despite similar fatty acid composition of the diet. In the second study, that included a larger training volume, differences in the fatty acid profile were also found in the skeletal muscle triglycerides. In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle. Furthermore, after a treatment period of three months, with diets with various dietary fat quality, the proportions of saturated fatty acids (14:0, 15:0 and 17:0) were higher and the proportion of 18:1 n-9 lower in subjects with a high intake of saturated fatty acids compared with subjects with a high intake of monounsaturated fatty acids. In addition subjects given n-3 supplementation had a higher proportion of total n-3 PUFA and lower n-6 PUFA in the skeletal muscle phospholipids than controls. Differences similar to those observed in the phospholipids were found in the triglycerides. In summary, these results suggest that regular aerobic physical activity and dietary fat quality influence the fatty acid composition of the skeletal muscle lipids, which may affect insulin sensitivity and glucose homeostasis.

Numerous diseases are associated with reduced antioxidant defence and oxidative stress. The antioxidant defence includes dietary and endogenous antioxidants and involves complex interactions between them. The effects of dietary factors on antioxidant status and oxidative stress of healthy humans were investigated in the studies described in this thesis. Assays of plasma antioxidant capacity encompass interactions between various antioxidants. Although uric acid has an unclear function as an antioxidant, it is a major determinant of antioxidant capacity. We measured antioxidant capacity in the presence and absence of uric acid to provide more information on the application of measures of antioxidant capacity. Individuals with high dietary intakes of various antioxidants and antioxidant rich foods, especially when combined, had higher plasma antioxidant capacities than those with lower antioxidant intakes. However, there were no associations between dietary intake of antioxidants or antioxidant rich foods and the plasma concentration of F2-isoprostanes, which is considered a reliable biomarker for oxidative stress. Intakes of various doses of a mixture of bilberry juice and black tea, rich in flavonoids for four weeks, increased antioxidant capacity in some groups, but urine levels of F2-isoprostanes were not affected. There were substantial individual variations in responses to the drinks related to baseline antioxidant capacity. Supplementation with eicosapentaenoic acid and docosahexaenoic acid decreased the plasma levels of F2-isoprostanes, but not prostaglandin F2α formation or antioxidant capacity. It was concluded that a high intake of foods rich in antioxidants is related to improved antioxidant status. After intake of foods rich in antioxidants, the antioxidant status may increase, but with considerable individual variation in the responses, which warrants further investigation. Lipid peroxidation in vivo is not easily affected by dietary antioxidants in healthy humans. Although n-3 fatty acids are highly unsaturated, they reduce nonenzymatic free radical-catalyzed lipid peroxidation, but not enzymatic lipid peroxidation.

Dietary n-3 polyunsaturated fatty acids (PUFA) have been shown to potently attenuate T cell-mediated inflammation, in part, by suppressing T cell activation and proliferation. Apoptosis is an important mechanism for preventing chronic inflammation by maintaining T cell homeostasis through the contraction of populations of activated T cells. We hypothesized that dietary n-3 PUFA would promote T cell apoptosis, thus, providing an additional mechanism to explain the anti-inflammatory effects. We specifically examined activation-induced cell death (AICD) since it is the form of apoptosis associated with peripheral T cell deletion involved in immunological tolerance and T cell homeostasis. Female C57BL/6 mice were fed diets containing either n-6 PUFA (control) or n-3 PUFA for 14 d. Splenic T cells were stimulated with CD3/CD28, CD3/PMA, or PMA/Ionomycin for 48 h followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide and flow cytometry. Cytokine analyses revealed that n-3 PUFA enhanced AICD only in T cells expressing a Th1-like cytokine profile (high IFN, low IL-4) compared to mice fed the n-6 PUFA control diet. Dietary n-3 PUFA significantly altered the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in T cell membranes. To examine the apparently selective effect of dietary n-3 PUFA on AICD in Th1 cells, CD4+ T cells were polarized in vitro to a Th1 phenotype by culture with IL-4, IL-2, and IL-12 for 2 d, followed by culture with IL-2 and IL-12 for 3 d in the presence of diet-matched homologous mouse serum (MS) to prevent loss of cell membrane fatty acids. Following polarization and reactivation, we observed that n-3 PUFA enhanced Th1 polarization and AICD only in cells cultured in the presence of MS, but not in fetal bovine serum. The n-3 PUFA enhancement of Th1 polarization and AICD was associated with the maintenance of diet-induced changes in EPA (20:5n-3) and DHA (22:6n-3) in plasma T cell membrane lipid rafts. Overall, these results suggest that dietary n-3 PUFA enhance both the polarization and deletion of pro-inflammatory Th1 cells, possibly as a result of alterations in lipid raft fatty acid composition.

No description available.

A oviposição é um estágio vulnerável do ciclo de vida de carrapatos. Rhipicephalus microplus, como todos Ixodidae e Argasidae, possui uma glândula especializada, o órgão de Gené, que produz uma cera que é depositada na superfície do ovo durante a oviposição. Além de restringir a perda excessiva de água, a cera atua como uma barreira contra o ataque de organismos invasores. Em R.microplus, como em outros carrapatos, há poucos estudos demonstrando atividade antimicrobiana em ovos. Ainda mais, não há na literatura relato de atividade antibiofilme em ovos de carrapatos e nem mesmo em qualquer outro artrópode. O objetivo do presente trabalho foi avaliar a hipótese da existência de mecanismos de defesa em ovos de R. microplus contra biofilmes bacterianos. O extrato água/metanol da cera dos ovos apresentou atividade contra o biofilme de Pseudomonas aeruginosa sem afetar a sua viabilidade. Esse extrato também demonstrou efeito antibiótico contra Staphylococcus epidermidis. Nós identificamos a molécula com ambas atividades (antibiofilme e antibiótica) como N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucina (boophiline). Na busca por possíveis mecanismos responsáveis pelo efeito antibiofilme de boophiline contra P. aeruginosa, 14 genes foram analisados por qRT-PCR. Boophiline inibe a expressão de fliC (flagelo) e cdrA (componente estrutural da matriz), cujos produtos são necessários para a formação do biofilme de P. aeruginosa. Monosfosfato de guanosina dimérico cíclico (c-di-GMP) é um importante segundo mensageiro característico de bactérias Gram-negativas. Altos níveis intracelulares de c-di-GMP promovem o estilo de vida séssil enquanto baixos níveis induzem o comportamento móvel. De acordo com essa afirmação, nós encontramos que boophiline aumenta a motilidade swarming de P. aeruginosa. Desta forma, nos questionamos se o mecanismo de ação de boophiline estaria envolvido com c-di-GMP já que o sistema quorum sensing não foi afetado pela molécula. Interessantemente, quando os níveis de c-di-GMP foram aumentados pela superexpressão de uma diguanilato ciclase, boophiline não inibiu efetivamente a formação de biofilme. Uma explicação para esse resultado é que boophiline interfere em uma via específica regulada por c-di-GMP, o que explicaria não termos obtido um decréscimo no nível total deste segundo mensageiro. Contrariamente, boophiline foi bactericida contra S. epidermidis. Mudanças morfológicas significativas foram observadas em células tratadas com a molécula, as quais foram severamente danificadas. Boophiline levou a formação anormal de septo, rompimento da membrana bacteriana e extravasamento do material intracelular. Adicionalmente avaliamos o potencial antibiofilme e anti-protozoário de filtrados de cultura obtidos de bactérias isoladas de tecidos de R. microplus. Quatorze filtrados de cultura bacteriano apresentaram notável atividade contra o biofilme de P. aeruginosa e S. epidermidis e foram citotóxicos contra Tritrichomonas foetus. Nosso trabalho é pioneiro em demonstrar a existência de proteção contra biofilmes em ovos de carrapatos bem como de bactérias associadas a carrapatos como produtoras de moléculas bioativas. Além disso, nós demonstramos que boophiline é uma nova molécula antibiofilme, sendo a primeira vez relatado na literatura que um composto age inibindo cdrA. Os dados obtidos em nosso estudo poderiam estimular novas abordagens em áreas como fisiologia e controle de artrópodes, genética e fisiologia de microrganismos e controle de biofilmes. / The oviposition is a vulnerable stage of the tick life cycle. Rhipicephalus microplus, as all Ixodidae and Argasidae, has a specialized gland, the Gene’s organ, which produce a wax that is smeared on egg surface during oviposition. In addition to restricting excessive water loss, wax acts as a barrier to attack by invading organisms. In R. microplus, as in other ticks, there are few studies showing antimicrobial activity in eggs. Moreover, there is no report of antibiofilm activity in tick eggs nor in any other arthropod. The objective of our study was to evaluate the hypothesis of the existence of defense mechanisms against bacterial biofilms in R. microplus eggs. The eggs wax water/methanol extract showed activity against Pseudomonas aeruginosa biofilm without affecting its viability. This extract also presented an antibiotic effect against Staphylococcus epidermidis. We have identified the molecule anti-biofilm and antibiotic as N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucine (boophiline). In the search for possible mechanisms responsible by antibiofilm effect of boophiline against P. aeruginosa, 14 genes were evaluated by qRT-PCR. We showed that boophiline inhibits the expression of fliC (flagellum) and cdrA (matrix structural component), whose products are necessary for biofilm formation in P. aeruginosa. Bis-(3’–5’)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an important second messenger, characteristic of Gram-negative bacteria. High intracellular levels of c-di-GMP promote a sessile mode of growth, while low levels promote motile behavior. In line with this, we found that boophiline increases swarming motility, which raised the question whether it acts by altering c-di-GMP levels. Interestingly, when c-di-GMP levels were increased by overexpression of a diguanilate cyclase, boophiline no longer inhibited biofilm formation. One explanation for these results is that boophiline interferes with a specific c-di-GMP-regulated pathway, which would explain we have not obtained a decrease in the total level of this second messenger. Conversely, boophiline had a bactericidal effect against S. epidermidis. Significant morphological changes were observed in the boophiline-treated cells, which appeared to be severely damaged. Boophiline was found to cause abnormal septum formation, bacterial membrane disruption, and extravasation of intracellular material. Additionally, our work also aimed to evaluate the potential antibiofilm and anti-protozoa of culture filtrates obtained from bacteria isolated of R. microplus tissues. Fourteen bacterial culture filtrates showed remarkable activity against of P. aeruginosa and S. epidermidis biofilms, and were cytotoxic against Tritrichomonas foetus. Our work is pioneer in demonstrating the existence of protection mechanisms in tick eggs against biofilms, and ticks-associated bacteria as producers of bioactive molecules. Furthermore, we demonstrated that boophiline is a new antibiofilm molecule, and is the first reported in the literature that a molecule inhibits cdrA. The data obtained in our study could stimulate new approaches in areas such as the physiology and control of arthropods, the genetics and physiology of microorganisms, and biofilm control.

A oviposição é um estágio vulnerável do ciclo de vida de carrapatos. Rhipicephalus microplus, como todos Ixodidae e Argasidae, possui uma glândula especializada, o órgão de Gené, que produz uma cera que é depositada na superfície do ovo durante a oviposição. Além de restringir a perda excessiva de água, a cera atua como uma barreira contra o ataque de organismos invasores. Em R.microplus, como em outros carrapatos, há poucos estudos demonstrando atividade antimicrobiana em ovos. Ainda mais, não há na literatura relato de atividade antibiofilme em ovos de carrapatos e nem mesmo em qualquer outro artrópode. O objetivo do presente trabalho foi avaliar a hipótese da existência de mecanismos de defesa em ovos de R. microplus contra biofilmes bacterianos. O extrato água/metanol da cera dos ovos apresentou atividade contra o biofilme de Pseudomonas aeruginosa sem afetar a sua viabilidade. Esse extrato também demonstrou efeito antibiótico contra Staphylococcus epidermidis. Nós identificamos a molécula com ambas atividades (antibiofilme e antibiótica) como N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucina (boophiline). Na busca por possíveis mecanismos responsáveis pelo efeito antibiofilme de boophiline contra P. aeruginosa, 14 genes foram analisados por qRT-PCR. Boophiline inibe a expressão de fliC (flagelo) e cdrA (componente estrutural da matriz), cujos produtos são necessários para a formação do biofilme de P. aeruginosa. Monosfosfato de guanosina dimérico cíclico (c-di-GMP) é um importante segundo mensageiro característico de bactérias Gram-negativas. Altos níveis intracelulares de c-di-GMP promovem o estilo de vida séssil enquanto baixos níveis induzem o comportamento móvel. De acordo com essa afirmação, nós encontramos que boophiline aumenta a motilidade swarming de P. aeruginosa. Desta forma, nos questionamos se o mecanismo de ação de boophiline estaria envolvido com c-di-GMP já que o sistema quorum sensing não foi afetado pela molécula. Interessantemente, quando os níveis de c-di-GMP foram aumentados pela superexpressão de uma diguanilato ciclase, boophiline não inibiu efetivamente a formação de biofilme. Uma explicação para esse resultado é que boophiline interfere em uma via específica regulada por c-di-GMP, o que explicaria não termos obtido um decréscimo no nível total deste segundo mensageiro. Contrariamente, boophiline foi bactericida contra S. epidermidis. Mudanças morfológicas significativas foram observadas em células tratadas com a molécula, as quais foram severamente danificadas. Boophiline levou a formação anormal de septo, rompimento da membrana bacteriana e extravasamento do material intracelular. Adicionalmente avaliamos o potencial antibiofilme e anti-protozoário de filtrados de cultura obtidos de bactérias isoladas de tecidos de R. microplus. Quatorze filtrados de cultura bacteriano apresentaram notável atividade contra o biofilme de P. aeruginosa e S. epidermidis e foram citotóxicos contra Tritrichomonas foetus. Nosso trabalho é pioneiro em demonstrar a existência de proteção contra biofilmes em ovos de carrapatos bem como de bactérias associadas a carrapatos como produtoras de moléculas bioativas. Além disso, nós demonstramos que boophiline é uma nova molécula antibiofilme, sendo a primeira vez relatado na literatura que um composto age inibindo cdrA. Os dados obtidos em nosso estudo poderiam estimular novas abordagens em áreas como fisiologia e controle de artrópodes, genética e fisiologia de microrganismos e controle de biofilmes. / The oviposition is a vulnerable stage of the tick life cycle. Rhipicephalus microplus, as all Ixodidae and Argasidae, has a specialized gland, the Gene’s organ, which produce a wax that is smeared on egg surface during oviposition. In addition to restricting excessive water loss, wax acts as a barrier to attack by invading organisms. In R. microplus, as in other ticks, there are few studies showing antimicrobial activity in eggs. Moreover, there is no report of antibiofilm activity in tick eggs nor in any other arthropod. The objective of our study was to evaluate the hypothesis of the existence of defense mechanisms against bacterial biofilms in R. microplus eggs. The eggs wax water/methanol extract showed activity against Pseudomonas aeruginosa biofilm without affecting its viability. This extract also presented an antibiotic effect against Staphylococcus epidermidis. We have identified the molecule anti-biofilm and antibiotic as N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucine (boophiline). In the search for possible mechanisms responsible by antibiofilm effect of boophiline against P. aeruginosa, 14 genes were evaluated by qRT-PCR. We showed that boophiline inhibits the expression of fliC (flagellum) and cdrA (matrix structural component), whose products are necessary for biofilm formation in P. aeruginosa. Bis-(3’–5’)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an important second messenger, characteristic of Gram-negative bacteria. High intracellular levels of c-di-GMP promote a sessile mode of growth, while low levels promote motile behavior. In line with this, we found that boophiline increases swarming motility, which raised the question whether it acts by altering c-di-GMP levels. Interestingly, when c-di-GMP levels were increased by overexpression of a diguanilate cyclase, boophiline no longer inhibited biofilm formation. One explanation for these results is that boophiline interferes with a specific c-di-GMP-regulated pathway, which would explain we have not obtained a decrease in the total level of this second messenger. Conversely, boophiline had a bactericidal effect against S. epidermidis. Significant morphological changes were observed in the boophiline-treated cells, which appeared to be severely damaged. Boophiline was found to cause abnormal septum formation, bacterial membrane disruption, and extravasation of intracellular material. Additionally, our work also aimed to evaluate the potential antibiofilm and anti-protozoa of culture filtrates obtained from bacteria isolated of R. microplus tissues. Fourteen bacterial culture filtrates showed remarkable activity against of P. aeruginosa and S. epidermidis biofilms, and were cytotoxic against Tritrichomonas foetus. Our work is pioneer in demonstrating the existence of protection mechanisms in tick eggs against biofilms, and ticks-associated bacteria as producers of bioactive molecules. Furthermore, we demonstrated that boophiline is a new antibiofilm molecule, and is the first reported in the literature that a molecule inhibits cdrA. The data obtained in our study could stimulate new approaches in areas such as the physiology and control of arthropods, the genetics and physiology of microorganisms, and biofilm control.