<p>Despite the advanced knowledge of the mechanisms of influenza infection and improved vaccines, Influenza A Virus still causes a life-threatening respiratory disease, especially during pandemics. Past investigations have proposed a synergism between Influenza A virus and a simultaneous or subsequent bacterial superinfection as the predominant cause of death. The recent development of animal models to study these heterologous infections has shed light onto the diverse mechanisms by which Influenza A Virus may increase the susceptibility to contract a secondary bacterial infection. These studies suggested an important role for the innate immune system in mediating such disease. We developed a model of heterologous infection combining Influenza A Virus and <em>Bordetella parapertussis</em> that demonstrated a critical role for MIP-2 to drive pulmonary neutrophilia in the pathology associated with bacterial superinfection of influenza. However, the origin of this increased MIP-2 production and the mechanisms underlying the immunopathology remained to be elucidated. The present studies proposed IL-1β overproduction as the upstream cause of the increased MIP-2 production observed in heterologous infection. This exaggerated IL-1β production was likely related to the increased bacterial burden observed in heterologously infected mice. This study also demonstrated that reduction in IL-1β production by blockade of the inflammasome seemed to provide an improvement in the clinical symptoms and the immunopathology of the disease. Thus, interventions to attenuate the exacerbated bacterial burden and the inflammatory responses derived from the subsequent IL-1β overproduction should be further investigate as possible therapeutic approaches to treat bacterial superinfections.</p> / Master of Science (MSc)

No description available.

Ainda que existam diversos registros de formas extremas de dimorfismo sexual, a função do alongado quarto par de pernas nos machos de muitas espécies de opiliões permanece desconhecida. Neste estudo, testamos quatro previsões sobre a hipótese de que a seleção sexual está direcionando o alongamento do quarto par de pernas nos machos de Longiperna zonata e Promitobates ornatus: (1) o coeficiente alométrico do comprimento do fêmur IV em machos será maior do que o das fêmeas; (2) machos com pernas IV mais compridas vão residir próximos a grupos de fêmeas; (3) machos envolvidos em interações agressivas terão fêmures mais compridos do que o tamanho médio da população; (4) a diferença de tamanho de perna entre os oponentes será menor do que a diferença esperada entre pares de machos escolhidos ao acaso na população. Como o previsto, o coeficiente alométrico do fêmur IV foi significativamente maior em machos do que em fêmeas nas duas espécies. O comprimento do fêmur IV está positivamente relacionado à chance de um macho ser encontrado próximo a um grupo de fêmeas. Finalmente, a média do comprimento do fêmur IV dos machos envolvidos em brigas foi significativamente maior que a de machos selecionados ao acaso da população. Adicionalmente, a média da diferença de tamanho entre pares de machos que brigaram foi significativamente menor que a média da diferença de tamanho de perna entre pares de machos selecionados ao acaso na população. Assim, a seleção sexual na forma de competição entre machos parece estar direcionando o dimorfismo sexual extremo no comprimento do fêmur nessas duas espécies de opiliões. / Although there are many reports of extreme forms of sexual dimorphism in harvestmen, the function of the elongated fourth pair of legs in males of many species remains unknown. We tested four predictions to address the hypothesis that sexual selection is driving the enlargement of the fourth pair of legs in males of Longiperna zonata and Promitobates ornatus: (1) the allometric coefficient of femur IV length in males will be higher than in females; (2) males with longer legs IV will reside closer to groups of females; (3) males involved in aggressive interactions will have longer femur IV than the population average size; (4) the size difference between contenders will be smaller than the difference expected between randomly chosen pairs of males in the population. As predicted, the allometric coefficient of femur IV length was significantly higher in males than in females of both species. Femur IV length was positively related to the chance of a male being found close to a group of females. Finally, the mean femur IV length of the males involved in fights was significantly larger than the mean of random samples of males from the population, and the average difference between male contenders was smaller than the average random expected difference of the population. Therefore, sexual selection in the form of male-male competition seems to be driving the extreme sexual dimorphism in femur length in these species.

Ainda que existam diversos registros de formas extremas de dimorfismo sexual, a função do alongado quarto par de pernas nos machos de muitas espécies de opiliões permanece desconhecida. Neste estudo, testamos quatro previsões sobre a hipótese de que a seleção sexual está direcionando o alongamento do quarto par de pernas nos machos de Longiperna zonata e Promitobates ornatus: (1) o coeficiente alométrico do comprimento do fêmur IV em machos será maior do que o das fêmeas; (2) machos com pernas IV mais compridas vão residir próximos a grupos de fêmeas; (3) machos envolvidos em interações agressivas terão fêmures mais compridos do que o tamanho médio da população; (4) a diferença de tamanho de perna entre os oponentes será menor do que a diferença esperada entre pares de machos escolhidos ao acaso na população. Como o previsto, o coeficiente alométrico do fêmur IV foi significativamente maior em machos do que em fêmeas nas duas espécies. O comprimento do fêmur IV está positivamente relacionado à chance de um macho ser encontrado próximo a um grupo de fêmeas. Finalmente, a média do comprimento do fêmur IV dos machos envolvidos em brigas foi significativamente maior que a de machos selecionados ao acaso da população. Adicionalmente, a média da diferença de tamanho entre pares de machos que brigaram foi significativamente menor que a média da diferença de tamanho de perna entre pares de machos selecionados ao acaso na população. Assim, a seleção sexual na forma de competição entre machos parece estar direcionando o dimorfismo sexual extremo no comprimento do fêmur nessas duas espécies de opiliões. / Although there are many reports of extreme forms of sexual dimorphism in harvestmen, the function of the elongated fourth pair of legs in males of many species remains unknown. We tested four predictions to address the hypothesis that sexual selection is driving the enlargement of the fourth pair of legs in males of Longiperna zonata and Promitobates ornatus: (1) the allometric coefficient of femur IV length in males will be higher than in females; (2) males with longer legs IV will reside closer to groups of females; (3) males involved in aggressive interactions will have longer femur IV than the population average size; (4) the size difference between contenders will be smaller than the difference expected between randomly chosen pairs of males in the population. As predicted, the allometric coefficient of femur IV length was significantly higher in males than in females of both species. Femur IV length was positively related to the chance of a male being found close to a group of females. Finally, the mean femur IV length of the males involved in fights was significantly larger than the mean of random samples of males from the population, and the average difference between male contenders was smaller than the average random expected difference of the population. Therefore, sexual selection in the form of male-male competition seems to be driving the extreme sexual dimorphism in femur length in these species.

Introdução. A progressão da síndrome metabólica (SMet) para a doença cardiovascular é complexa, multifatorial e pode estar associada, em parte, com a hiperativação simpática e com a diminuição da sensibilidade barorreflexa (SBR), mecanismos fortemente associados à hipertensão arterial (HAS). Adicionalmente, na hipertensão a resposta da pressão arterial (PA) durante o teste de esforço cardiopulmonar máximo (TECP) e na pressão arterial de 24h (MAPA) está prejudicada. Não é conhecido se pacientes com SMet mas sem hipertensão, apresentam estes prejuízos. Hipóteses. Pacientes com SMet com nível normal de PA clínica apresentam:(1) Resposta aumentada da PA pico e da PA de recuperação em resposta ao exercício máximo; (2) Prejuízo na PA de 24 horas Além disso, analisamos se estas alterações se correlacionam com a atividade nervosa simpática muscular (ANSM) e com a SBR. Métodos. Foram selecionados 72 pacientes recém-diagnosticados com SMet (ATP III), alocados em 3 grupos conforme a classificação da PA (segundo as Diretrizes 2013 ESH/ESC):, SMet hipertensos (HT, n=16, 51±9 anos, 33±4 kg/m2), SMet pré-hipertensos (PHT, n=29, 47±10 anos, 31±3 kg/m2) e SMet normotensos (NT, n=27, 46±7 anos, 32±4 kg/m2). Um grupo controle (C, n=19, 48±2 anos, 25±2 kg/m2) pareado por gênero e idade foi envolvido no estudo. Foram avaliados: a ANSM (microneurografia); a SBR (análise das flutuações espontâneas da PA sistólica e FC) para aumentos (SBR+) e diminuições da PA (SBR-); medidas auscultatórias da PA no pré-teste, pico, 1°, 2° e 4° min de recuperação (TECP); e PAS e PAD de 24 horas, vigília, sono e despertar (MAPA de 24h). O estudo foi dividido em duas partes: Parte 1 - todos os grupos com SMet (HT, PHT e NT) e C foram estudados; e Parte 2 - somente o grupo SMet NT foi comparado ao C. Resultados - Parte 1. Os grupos SMet (HT, PHT e NT) foram semelhantes entre si e apresentaram prejuízo quando comparado ao grupo C nas características físicas, na capacidade física e nos fatores de risco da SMet. Na PAS pico atingida no TECP, o grupo SMet HT apresentou valores superiores quando comparado com SMet PHT, NT, e C (217±23 vs. 202±22; 195±17; 177±24 mmHg; respectivamente; P=0,03). Apresentaram resposta da PAS exagerada (PAS >190 mmHg para mulheres e > 210 mmHg para homens) 81% no grupo HT, 55% no PHT, 37% no NT e 21% no C. Na MAPA, SMet HT apresentou maior PA de 24h que os outros 3 grupos. (P < 0,001). A ANSM foi maior nos grupos SMet HT, PHT e NT quando comparados ao C (33±7; 30±7; 29±6; vs. 18±1 disparos/min, respectivamente, P < 0,001). Somente o grupo SMet HT apresentou menor SBR+ quando comparado ao grupo C (6±3; 8±3; 9±3; vs. 11±5 mmHg/ms; P=0,002). Os grupos SMet HT e PHT apresentaram menor SBR-, enquanto SMet NT foi semelhante ao C (7±2; 9±4; 10±3; vs. 12±5 mmHg/ms; P < 0,05). Houve correlação entre a SBR- e a PAS pico (r=-0,32, P=0,04) com todos os sujeitos dos grupos da SMet e C. Resultados Parte 2. Exceto na PAS no 4º min de recuperação, o grupo SMet NT apresentou maior PAS e PAD comparado ao C em todos os momentos do TECP. O comportamento da PAS e PAD pela área sob a curva (ASC) total foi maior no SMet NT comparado ao C. Na MAPA de 24h, SMet NT apresentou menor PAD no sono que C. Além disso, SMet NT apresentou menor SBR+ e SBR- e maior ANSM comparado ao C. Interessantemente, no subgrupo de pacientes com SMet NT (n=10, 37%) que apresentou PAS pico exagerada a SBR- se correlacionou fortemente com a PAS pico (r=-0,70, P=0,02) e com a PAS no 1º min de recuperação (r=-0,73, P=0,04). Conclusão: Pacientes com SMet, mesmo normotensos, já apresentam resposta exacerbada da PAS e da PAD durante o TECP, dos quais 40% com PAS pico exagerada. A disfunção autonômica pode explicar, pelo menos em parte, esta reposta exacerbada / Introduction. The progression of the metabolic syndrome (MetS) to cardiovascular disease is complex, multifactorial and may be associated in part with sympathetic hyperactivation and reduced baroreflex sensitivity (BRS), mechanisms strongly associated with arterial hypertension (AH). Additionally, in hypertension, the BP response during the maximal cardiopulmonary exercise test (CPET) and 24h BP (ABPM) is impaired. It is not known whether patients with MetS but without hypertension present those damages. Hypotheses. Patients with MetS with normal clinical BP level present: (1) Increased response of peak BP and recovery BP in response to maximal exercise; (2) Impaired 24 hour BP. In addition, we analyzed if those changes are associated with muscle sympathetic nerve activity (MSNA) and BRS. Methods. We selected 72 newly diagnosed patients with MetS (ATP III), subdivided in 3 groups according to the BP classification (according to the ESH/ESC Guidelines): hypertensive MetS (HT, n=16, 51±9 years, 33±4 kg/m2), pre-hypertensive MetS (PHT, n=29, 47± 10 years, 31±3 kg/m2) and normotensive MetS (NT, n= 27, 46±7 years, 32±4 kg/m2). A control group (C, n=19, 48±2 years, 25±2 kg/m2) paired by gender and age was involved in the study. The following were evaluated: the MSNA (microneurography); BRS (analysis of spontaneous fluctuations of systolic BP and HR) for increases to BP (SBR+) and for decreases to BP (SBR-); BP auscultatory measurements in the pre-test, peak, 1st, 2nd and 4th min of recovery (CPET); and SBP and DBP of 24 hours, wakefulness, sleep and awakening (24-hour ABPM). The study was divided into two parts: Part 1. All groups with MetS (HT, PHT and NT) were studied; and C group. Part 2. Only the NT MetS group was compared to the C. Results Part 1. The MetS groups (HT, PHT and NT) were similar and were impaired compared to group C in physical characteristics, physical capacity and risk factors of MetS. In the peak SBP reached at CPET, HT MetS group presented higher values when compared to PHT and NT MetS groups and C (217±23 vs. 202±22, 195±17, 177±-24 mmHg, respectively, P=0.03). There was an exaggerated SBP response (SBP > 190 mmHg for women and > 210 mmHg for men) in 81% of the HT group, 55% of the PHT, 37% of the NT and 21% of the C group. In the ABPM, HT MetS had a higher 24-hour BP than the other 3 groups (P < 0.001). The MSNA was higher in HT, PHT and NT MetS groups when compared to C (33±7, 30±7, 29±6, vs. 18±1 burst/min, respectively, P < 0.001). Only the HT MetS group showed lower SBR+ compared to C (6±3, 8±3, 9±3, vs. 11±5 mmHg/ms, P=0.002). The HT and PHT MetS groups presented lower SBR-, while NT MetS was similar to C (7±2; 9 ±4; 10±3, vs. 12±5 mmHg/ms; P < 0.05). There was a correlation between SBR- and peak SBP (r= -0.32, P=0.04) with all subjects from the MetS and C groups. Results Part 2. Except for SBP in the 4th min of recovery, NT MetS presented higher SBP and DBP compared to C at all moments of the CPET. The SBP and DBP responses by AUC analysis were higher in NT MetS compared to C. In 24h ABPM, NT MetS presented lower DBP in the sleep than in C. In addition, NT MetS presented decreased SBR+ and SBR- and increased MSNA compared with C. Interestingly, in the NT MetS subgroup of patients (n=10, 37%) who showed an exaggerated peak SBP, showed a negative correlation between BRS- and peak SBP (r=-.70; P=0.01) and SBP at 1st minute of recovery (r=.73; P=0.04). Conclusion. Patients with MetS, even normotensive, already present an exacerbated SBP and DBP response during CPET, of which 40% with exaggerated peak SBP. Autonomic dysfunction may explain, at least in part, this exacerbated response

Introdução. A progressão da síndrome metabólica (SMet) para a doença cardiovascular é complexa, multifatorial e pode estar associada, em parte, com a hiperativação simpática e com a diminuição da sensibilidade barorreflexa (SBR), mecanismos fortemente associados à hipertensão arterial (HAS). Adicionalmente, na hipertensão a resposta da pressão arterial (PA) durante o teste de esforço cardiopulmonar máximo (TECP) e na pressão arterial de 24h (MAPA) está prejudicada. Não é conhecido se pacientes com SMet mas sem hipertensão, apresentam estes prejuízos. Hipóteses. Pacientes com SMet com nível normal de PA clínica apresentam:(1) Resposta aumentada da PA pico e da PA de recuperação em resposta ao exercício máximo; (2) Prejuízo na PA de 24 horas Além disso, analisamos se estas alterações se correlacionam com a atividade nervosa simpática muscular (ANSM) e com a SBR. Métodos. Foram selecionados 72 pacientes recém-diagnosticados com SMet (ATP III), alocados em 3 grupos conforme a classificação da PA (segundo as Diretrizes 2013 ESH/ESC):, SMet hipertensos (HT, n=16, 51±9 anos, 33±4 kg/m2), SMet pré-hipertensos (PHT, n=29, 47±10 anos, 31±3 kg/m2) e SMet normotensos (NT, n=27, 46±7 anos, 32±4 kg/m2). Um grupo controle (C, n=19, 48±2 anos, 25±2 kg/m2) pareado por gênero e idade foi envolvido no estudo. Foram avaliados: a ANSM (microneurografia); a SBR (análise das flutuações espontâneas da PA sistólica e FC) para aumentos (SBR+) e diminuições da PA (SBR-); medidas auscultatórias da PA no pré-teste, pico, 1°, 2° e 4° min de recuperação (TECP); e PAS e PAD de 24 horas, vigília, sono e despertar (MAPA de 24h). O estudo foi dividido em duas partes: Parte 1 - todos os grupos com SMet (HT, PHT e NT) e C foram estudados; e Parte 2 - somente o grupo SMet NT foi comparado ao C. Resultados - Parte 1. Os grupos SMet (HT, PHT e NT) foram semelhantes entre si e apresentaram prejuízo quando comparado ao grupo C nas características físicas, na capacidade física e nos fatores de risco da SMet. Na PAS pico atingida no TECP, o grupo SMet HT apresentou valores superiores quando comparado com SMet PHT, NT, e C (217±23 vs. 202±22; 195±17; 177±24 mmHg; respectivamente; P=0,03). Apresentaram resposta da PAS exagerada (PAS >190 mmHg para mulheres e > 210 mmHg para homens) 81% no grupo HT, 55% no PHT, 37% no NT e 21% no C. Na MAPA, SMet HT apresentou maior PA de 24h que os outros 3 grupos. (P < 0,001). A ANSM foi maior nos grupos SMet HT, PHT e NT quando comparados ao C (33±7; 30±7; 29±6; vs. 18±1 disparos/min, respectivamente, P < 0,001). Somente o grupo SMet HT apresentou menor SBR+ quando comparado ao grupo C (6±3; 8±3; 9±3; vs. 11±5 mmHg/ms; P=0,002). Os grupos SMet HT e PHT apresentaram menor SBR-, enquanto SMet NT foi semelhante ao C (7±2; 9±4; 10±3; vs. 12±5 mmHg/ms; P < 0,05). Houve correlação entre a SBR- e a PAS pico (r=-0,32, P=0,04) com todos os sujeitos dos grupos da SMet e C. Resultados Parte 2. Exceto na PAS no 4º min de recuperação, o grupo SMet NT apresentou maior PAS e PAD comparado ao C em todos os momentos do TECP. O comportamento da PAS e PAD pela área sob a curva (ASC) total foi maior no SMet NT comparado ao C. Na MAPA de 24h, SMet NT apresentou menor PAD no sono que C. Além disso, SMet NT apresentou menor SBR+ e SBR- e maior ANSM comparado ao C. Interessantemente, no subgrupo de pacientes com SMet NT (n=10, 37%) que apresentou PAS pico exagerada a SBR- se correlacionou fortemente com a PAS pico (r=-0,70, P=0,02) e com a PAS no 1º min de recuperação (r=-0,73, P=0,04). Conclusão: Pacientes com SMet, mesmo normotensos, já apresentam resposta exacerbada da PAS e da PAD durante o TECP, dos quais 40% com PAS pico exagerada. A disfunção autonômica pode explicar, pelo menos em parte, esta reposta exacerbada / Introduction. The progression of the metabolic syndrome (MetS) to cardiovascular disease is complex, multifactorial and may be associated in part with sympathetic hyperactivation and reduced baroreflex sensitivity (BRS), mechanisms strongly associated with arterial hypertension (AH). Additionally, in hypertension, the BP response during the maximal cardiopulmonary exercise test (CPET) and 24h BP (ABPM) is impaired. It is not known whether patients with MetS but without hypertension present those damages. Hypotheses. Patients with MetS with normal clinical BP level present: (1) Increased response of peak BP and recovery BP in response to maximal exercise; (2) Impaired 24 hour BP. In addition, we analyzed if those changes are associated with muscle sympathetic nerve activity (MSNA) and BRS. Methods. We selected 72 newly diagnosed patients with MetS (ATP III), subdivided in 3 groups according to the BP classification (according to the ESH/ESC Guidelines): hypertensive MetS (HT, n=16, 51±9 years, 33±4 kg/m2), pre-hypertensive MetS (PHT, n=29, 47± 10 years, 31±3 kg/m2) and normotensive MetS (NT, n= 27, 46±7 years, 32±4 kg/m2). A control group (C, n=19, 48±2 years, 25±2 kg/m2) paired by gender and age was involved in the study. The following were evaluated: the MSNA (microneurography); BRS (analysis of spontaneous fluctuations of systolic BP and HR) for increases to BP (SBR+) and for decreases to BP (SBR-); BP auscultatory measurements in the pre-test, peak, 1st, 2nd and 4th min of recovery (CPET); and SBP and DBP of 24 hours, wakefulness, sleep and awakening (24-hour ABPM). The study was divided into two parts: Part 1. All groups with MetS (HT, PHT and NT) were studied; and C group. Part 2. Only the NT MetS group was compared to the C. Results Part 1. The MetS groups (HT, PHT and NT) were similar and were impaired compared to group C in physical characteristics, physical capacity and risk factors of MetS. In the peak SBP reached at CPET, HT MetS group presented higher values when compared to PHT and NT MetS groups and C (217±23 vs. 202±22, 195±17, 177±-24 mmHg, respectively, P=0.03). There was an exaggerated SBP response (SBP > 190 mmHg for women and > 210 mmHg for men) in 81% of the HT group, 55% of the PHT, 37% of the NT and 21% of the C group. In the ABPM, HT MetS had a higher 24-hour BP than the other 3 groups (P < 0.001). The MSNA was higher in HT, PHT and NT MetS groups when compared to C (33±7, 30±7, 29±6, vs. 18±1 burst/min, respectively, P < 0.001). Only the HT MetS group showed lower SBR+ compared to C (6±3, 8±3, 9±3, vs. 11±5 mmHg/ms, P=0.002). The HT and PHT MetS groups presented lower SBR-, while NT MetS was similar to C (7±2; 9 ±4; 10±3, vs. 12±5 mmHg/ms; P < 0.05). There was a correlation between SBR- and peak SBP (r= -0.32, P=0.04) with all subjects from the MetS and C groups. Results Part 2. Except for SBP in the 4th min of recovery, NT MetS presented higher SBP and DBP compared to C at all moments of the CPET. The SBP and DBP responses by AUC analysis were higher in NT MetS compared to C. In 24h ABPM, NT MetS presented lower DBP in the sleep than in C. In addition, NT MetS presented decreased SBR+ and SBR- and increased MSNA compared with C. Interestingly, in the NT MetS subgroup of patients (n=10, 37%) who showed an exaggerated peak SBP, showed a negative correlation between BRS- and peak SBP (r=-.70; P=0.01) and SBP at 1st minute of recovery (r=.73; P=0.04). Conclusion. Patients with MetS, even normotensive, already present an exacerbated SBP and DBP response during CPET, of which 40% with exaggerated peak SBP. Autonomic dysfunction may explain, at least in part, this exacerbated response

Pin-up images have played an important role in American culture, in both their illustrated and photographic configurations. The pin-up is viewed as a significant representational cultural artifact of idealistic and aspirational femininity and of consumerism and material wealth, especially reflective of the mid-twentieth century period in America spanning the 1930s to the 1960s. These images not only reflect great shifts in social mores and women’s social status, but also affected changes in both areas in turn. Furthermore, pin-up images internationally circulated in magazines, advertising and promotional material, contributed to the manner in which America was idealized in Europe and beyond. Crucially, they influenced how an eroticized and glamorous, yet unrealistic, example of femininity came to be generalized as a desirous model of femininity. In recent years there has been vital, though limited, scholarly research into the cultural and social impact of pin-up imagery, to which this thesis adds to. This thesis takes a genealogical approach, charting the development of popular female-centric “pin-up” imagery in America since the 1860s and up to the 1960s, and its resurgence since the 1980s onwards. In doing so this thesis aims to provide a social, political and cultural context to the emergence of a specific archetypal sexualized femininity, with the aim of challenging the tendency to dismiss sexualized imagery as “anti-feminist” or as trivial. Toward that end, I examine the complexity of intentions behind the production of “pin-up” images. In taking this revisionist approach I am better able to conclusively analyze the reasons for the resurgence and reappropriation of pin-up imagery in late-twentieth- and early-twenty-first-century popular culture, and consider what the gendered cultural implications may be.