Knee osteoarthritis (OA) is the commonest form of lower limb OA with a lifetime risk of over 40%. It is a disease characterised by symptoms such as pain and loss of function. In addition there are typical structural features on both radiographs and MRI. Knee OA represents a spectrum of disease, ranging from early preclinical cartilage change to established full thickness disease. Anteromedial knee OA is a particular phenotype of knee OA where disease is confined to the medial compartment. Whilst end stage arthritis is treated reliably with joint arthroplasty, those with early stage disease are treated with a variety of non- surgical interventions with varying success. This thesis is concerned with understanding the disease of patients that have early radiographic changes but symptoms not controlled by conservative measures. Up to 150 of these patients a year present to the Nuffield Orthopaedic Centre, Oxford. They have been described as being in the “Treatment Gap”. A series of validation studies were performed to determine the optimal method for diagnosing cartilage defects within the knee. The three commonest diagnostic methods were examined for their validity. Arthroscopic assessments of cartilage lesions demonstrated a moderate level of intra and inter observer reliability. In contrast, radiographs and MRI demonstrated high levels of reliability. When using MRI as a criterion standard, both radiographs and arthroscopic assessment were found to have poor accuracy. Based on the work in this thesis a formal definition of the cartilage changes exhibited in early knee OA was proposed. A cross sectional cohort of 100 patients with the symptoms and radiological features of early knee OA were identified. Their pain and function profile was compared to two comparison groups of patients at the end stage of knee OA (defined by the need for partial or total arthroplasty). In up to 78% of individual cases those with early OA had pain and function profiles as bad as those with end stage disease. The cross sectional symptoms of early knee OA demonstrate a marked discordance with their mild radiographic changes. The same cohort was extended to 125 patients. They were followed over one year with monthly PROM assessments to determine how symptoms change over time. 43% of patients experience a clinical improvement over 12 months, 31% experience a clinical deterioration and 26% remain unchanged. The range in OKS variation over 12 months was on average 12 points, with clinically relevant variation occurring on 45% of monthly measurements. Patients with early knee OA can expect to experience considerable variation in their symptoms over 12 months and this must be considered when planning interventions. A number of patients with early knee OA were noticed to demonstrate medial meniscal extrusion. Using data from the Osteo Arthritis Initiative (OAI) a nested case control study was designed to determine how the presence of meniscal extrusion in an otherwise normal knee affects the risk of developing knee OA over the next 48 months. This demonstrated an Odds Ratio of 3.5, suggesting that meniscal extrusion is a considerable risk factor for the development of OA. The presence of a knee injury or operative intervention to the index meniscus was shown to increase this risk. Many phenotypes of OA are known to demonstrate familial aggregation. In an attempt to determine where the earliest structural changes occur in medial compartment knee OA, a cohort of patients selected only for their family history of the disease were developed. This cohort was compared to spouse controls for the presence of knee OA, as well as meniscal extrusion and long leg alignment. In addition, a functional analysis of their cartilage was performed. This cohort was not shown to be at increased risk of disease compared to controls. Discussion of the possible reasons for this finding is presented. Early knee osteoarthritis is a considerable clinical problem. This thesis has aided the understanding of the condition by firstly defining the radiological description of these patients. Secondly, their cross sectional and longitudinal symptom profile have been described for the first time. In addition, the presence of an extruded meniscus has been demonstrated as a substantial risk factor for the disease. Finally, family history has not been demonstrated as a risk factor for the disease within the limits of the study described here. Future work has been proposed.

Platelet secretion is important for hemostasis and thrombosis. The components released are also involved in atherosclerosis, inflammation, angiogenesis, and tumor growth. Though the exact mechanism(s) of platelet secretion is still elusive, accumulating evidence demonstrates that SNAREs (Soluble N-ethylmaleimide Sensitive Factor Associated Receptor) and their regulatory partners are critical for platelet exocytosis. Formation of a trans-bilayer complex composed of one v-SNARE (i.e. VAMPs) and two t-SNAREs (i.e. syntaxin and SNAP-25-type) is minimally required for membrane fusion. Regulatory proteins control the rate and specificity of the complex assembly. VAMP-8 and SNAP-23 (a SNAP-25-type t-SNARE) are clearly important; however, the identity of the functional syntaxin has been controversial. Previous studies, using anti-syntaxin antibodies in permeabilized platelets, suggested roles for both syntaxin-2 and -4. These conclusions were experimentally tested using platelets from syntaxin knockout mice and from a Familial Hemophagocytic Lymphohistiocytosis type 4 (FHL4) patient that lacks syntaxin-11. Platelets from syntaxin-2 and syntaxin-4 single or double knockout mice had no significant secretion defect. However, platelets from the FHL4 patient had a robust defect, though their morphology, activation, and cargo levels appeared normal. Semi-quantitative western blotting showed that syntaxin-11 is the most abundant syntaxin in both human and murine platelets. Co-immunoprecipitation experiments showed that syntaxin-11 forms SNARE complexes with VAMP-8 and SNAP-23. These data conclusively demonstrate that syntaxin-11, but not syntaxin-2, or -4, is required for platelet exocytosis. We also show that a syntaxin binding protein, tomosyn-1, is important for platelet exocytosis and hemostasis. Tomosyn-1 was identified from platelet extracts using affinity chromatography, RT-PCR analysis, and western blotting analysis. Tomosyn-1 was co-immunoprecipitated with syntaxin-11/SNAP-23 from both resting and activated platelet extracts. Platelets from tomosyn-1-/- mice displayed a secretion defect, but their morphology and activation appeared normal. Tomosyn-1-/- mice showed impaired thrombus formation in two different injury models. Given the importance of platelet secretion to hemostasis, it is hoped that the insights gained from these studies in this dissertation will help to identify new and more valuable therapeutic targets to control clot formation.

Adolescent substance abuse represents a complex, difficult challenge in the United States. Substance addiction research requires rich contextualization that takes into account individual, familial, and community experiences. This project focuses on how adolescent girls' substance use interacts with risk and vulnerability. More specifically, how the social and biological body influences substance initiation and how local contexts and constraints effects recovery from addiction. The sample includes adolescent girls who are enrolled in substance abuse treatment programs. The methodological approach encompasses a mixture of quantitative and qualitative, including analysis of a nation-wide dataset, narrative interviews, participant observation, and case following. While the quantitative analysis was with the nation-wide dataset, the qualitative data are derived from a sample of adolescent girls in Tucson, Arizona. Risk is assessed along three axes, biocultural, familial, and structural. Biocultural risk examines the influence that an early pubertal developmental trajectory has on substance initiation. Familial risk analyzes how the culture and habitus of the family affects youth initiation of substance use. Structural risk highlights the continued vulnerability that youth who are raised in the `system' face and specifically their challenges to recovery after substance abuse treatment. Findings from the nation-wide sample include a significant relationship between pubertal timing and age of onset of substance use. In the Tucson sample, familial immersion in substance use was so extensive that girls were not only expected to begin using but also initiation of use became a 'rite of passage' within the family. Finally this research documents the unintended role the child welfare system plays as a structural impediment to girls' recovery from substance abuse.

Mutations found in genes encoding human Elongator complex subunits have been linked to neurodevelopmental disorders such as familial dysautonomia (FD), rolandic epilepsy and amyotrophic lateral sclerosis. In addition, loss-of-function mutations in genes encoding Elongator complex subunits cause defects in neurodevelopment and reduced neuronal function in both mice and nematodes. The Elongator complex is a conserved protein complex comprising six subunits (Elp1p-Elp6p) found in eukaryotes. The primary function of this complex in yeast is formation of the 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) side chains found on wobble uridines (U34) in tRNAs. The aim of this thesis is to investigate the physiological consequences of Elongator complex inactivation in humans and in the yeast Saccharomyces cerevisiae. Inactivation of the Elongator complex causes widespread defects in a multitude of different cellular processes in S. cerevisiae. Thus, we investigated metabolic alterations resulting from Elongator complex inactivation. We show that deletion of the S. cerevisiae ELP3 gene leads to widespread metabolic alterations. Moreover, all global metabolic alterations observed in the elp3Δ strain are not restored in the presence of elevated levels of hypomodified tRNAs that normally have the modified nucleoside mcm5s2U. Collectively, we show that modified wobble nucleosides in tRNAs are required for metabolic homeostasis. Elongator mutants display sensitivity to DNA damage agents, but the underlying mechanism explaining this sensitivity remains elusive. We demonstrate that deletion of the S. cerevisiae ELP3 gene results in post-transcriptional reduction of Ixr1p levels. Further, we show that the reduced Ixr1p levels prevent adequate Rnr1p levels upon treatment with DNA damage agents. These findings suggest that reduced Ixr1p levels could in part explain why Elongator mutants are sensitive to DNA damage agents. Depletion of Elongator complex subunits results in loss of wobble uridine modifications in plants, nematodes, mice and yeast. Therefore, we investigated whether patients with the neurodegenerative disease familial dysautonomia (FD), who have lower levels of the ELP1 protein, display reduced amounts of modified wobble uridine nucleosides. We show that tRNA isolated from brain tissue and fibroblast cell lines derived from FD patients have 64–71% of the mcm5s2U nucleoside levels observed in total tRNA from non-FD brain tissue and non-FD fibroblasts. Overall, these results suggest that the cause for the neurodegenerative nature of FD could be translation impairment caused by reduced levels of modified wobble uridine nucleosides in tRNAs. Thus, our results give new insight on the importance of modified wobble uridine nucleosides for neurodevelopment.

Faculty of Humanities School of Human and Community Development 0008716g Mashils@hotmail.com / This study explored the effects of extra-familial child sexual abuse on the victims’ primary caregivers. The study focused on the experiences of ten mothers whose children were raped during the six months that preceded the study, and they were drawn from Zamokuhle and Nthabiseng clinics in Soweto. A semi-structured individual interview was used to explore the implications of the rape on the primary caregivers’ psychological well being. The data was processed using qualitative content analysis as the methodology. Findings indicate that the children were raped in their everyday environment during their mothers’ absence. The majority of the perpetrators are trusted neighbours and some used violence to coerce the children into participating. Some children concealed the rapes from their mothers and they were threatened with punishment to facilitate disclosure. The primary caregivers responded with anger post-disclosure which was directed toward different parties. They blamed the children for withholding the rape and for failing to combat it, and the perpetrators for betraying them. The mothers’ anger was exacerbated by the failure of the justice system to bring the perpetrators to book, and other people whom the mothers felt should have protected their children. In terms of causal attribution, the respondents questioned their maternal role and felt that they did not provide their children with the necessary care and protection they needed. The primary caregivers also felt that the children could have prevented the rape if they behaved differently. The rape took a toll on the relationship the mothers had with their children as some became overprotective to compensate for the protection they never provided their children with. Most mothers displayed an inability to cope post-disclosure which suggests that child sexual abuse has adverse effects on the psychological well-being of noniv offending mothers. For purposes of clarity, the word “mother” will be used interchangeably with “primary caregiver” throughout the study.

Orientador: José Paes de Oliveira Filho / Resumo: O estudo das doenças de origem genética em animais domésticos se torna cada vez mais relevante, sobretudo em cães, uma vez que estes animais podem servir como modelos experimentais para certas doenças em humanos. Além disso, o reconhecimento clínico de algumas destas enfermidades pode ser um entrave ao Médico Veterinário e em algumas ocasiões o teste genético que confirmaria a etiologia não está disponível no país. A Nefropatia Familiar (FN) causada pela mutação c.115A>T no gene colágeno tipo 4α4 (COL4A4), e a Atrofia Progressiva da Retina (prcd-PRA), causada pela mutação c.5G>A no gene da degeneração cone-bastonete progressiva (PRCD), se destacam entre as principais enfermidades hereditárias de origem genética que acometem cães da raça Cocker Spaniel Inglês (CSI). Até o momento a prevalência destas enfermidades nesta raça não havia sido verificada no Brasil, sendo assim, o objetivo deste estudo foi avaliar a frequência alélica destas mutações no CSI. Para tanto, foram genotipados 220 e 216 CSI para a prcd-PRA e FN, respectivamente. Fragmentos do DNA, contendo cada uma das mutações, foram amplificados por reação em cadeia da polimerase e submetidos ao sequenciamento gênico direto. A frequência alélica da mutação c.115A>T no gene COL4A4 foi de 0,9% e da mutaçao c.5G>A no gene PRCD foi de 25,5%. Tais valores enfatizam a importância da realização dos testes de genotipagem nos cães da raça CSI como método de diagnóstico precoce principalmente para a orientação dos acasalamentos v... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The study of genetic diseases in domestic animals has become more relevant, especially in dogs, once these animals can serve as experimental models in the study of some human genetic diseases. Besides, these diseases can be hard to recognize on their clinical signs by the practitioners, and the genetic tests that can confirm them are usually available only abroad. Familial Nephropathy (FN) due to the mutation c.115A> T in the 4α4 collagen gene (COL4A4), and Progressive Retinal Atrophy (prcd-PRA) due to the mutation c.5G> A in the progressive rod cone degeneration gene (PRCD), are important genetic diseases of English Cocker Spaniel dogs (ECS) dogs. Since the prevalence of these diseases wasn’t verified in Brazil so far, this study aims to evaluate the allelic frequencies of the mutations c.115A>T in the COL4A4 gene and c.5G>A in the PRCD gene in English Cocker Spaniel dogs. For that, purified DNA from blood samples or buccal swab from 220 and 216 ECS for prcd-PRA and FN, respectively. DNA fragments with the mutation region were amplified by polymerase chain reaction and submitted to direct genomic sequencing. The allelic frequency of the mutation c.115A>T in the COL4A4 gene was 0.9% and the c.5G>A in the PRCD gene was 25.5%. The results in this study emphasizes the importance to realize the genotyping test in ECS as an early diagnostic test, not only for trying an improvement of the affected dogs’ life quality but also for breeding orientation to avoid clinical cases of the d... (Complete abstract click electronic access below) / Mestre

This study explores the silencing of familial spaces in Chimamanda Ngozi Adichie’s Purple Hibiscus. It probes into how the familial space is invested with religiosity: how ritual and norm structure and silence familial spaces and how transcendence from these spaces can be achieved through elements of laughter, music and sexuality. The study uses post-colonial theories, concepts of familial ideology and familial theory to read the text. The introductory chapter provides a politico-historical background of the text, then a literary historiography of how the familial trope has been used in African literature with special focus on Achebe. The chapter also outlines the theoretical framework of the study while anticipating the issues to be dealt with. Chapter two focuses on how the familial space is invested with religious rituals and how these silence the familial space. Chapter three examines how augmentation out of the silenced familial spaces works through elements of laughter, sexuality and music. Chapter four investigates the family as a portrait of the state and most significantly how these two institutions are portrayed to be in a complex relationship. The study’s conclusion is that the family can be used as an alternative site for discourses of marginality and can give a nuanced critique of the postcolony.

Ce travail se propose d´étudier le rapport entre la filiation et l´écriture de l´Histoire chez deux écrivains contemporains : le Français Patrick Modiano et la romancière allemande Monika Maron. Chez ces auteurs, le « roman familial » constitue un accès privilégié à l´Histoire. Après avoir replacé les deux écrivains dans leurs paysages littéraires respectifs et précisé des notions utiles comme l´autobiographie, l´autofiction et le roman familial, le travail s´attache à dégager les figures de la filiation dans les deux œuvres en confrontant les données biographiques à leurs transpositions romanesques. Une étude des structures narratives montre ensuite que le passé et l´Histoire n´interviennent pas seulement au niveau thématique mais influencent jusqu´à la forme du récit. Un intérêt tout particulier est porté aux modalités d´une écriture de l´Histoire qui se révèle complexe, entre objectivité historique, fantasme et fiction. L´approche par la filiation confère à l´écriture de l´Histoire une forte dimension mémorielle. La question de l´identité se pose alors en termes d´héritage familial et historique. En cela, Patrick Modiano et Monika Maron s´inscrivent dans l´ensemble plus large d´une littérature « générationnelle » de la seconde moitié du XXe siècle. / This study deals with the relationship between filiation and the writing of history in the works of two contemporary authors, the French author Patrick Modiano and the German novelist Monika Maron. Both authors approach history mainly through family romance. First, the two authors are situated in their respective literary environment, and some key notions are developed in detail, such as autobiography, autofiction, and family romance. On that basis, the fictional characters that bear marks of filiation are portrayed by confronting biographical facts with their fictional transpositions. A subsequent analysis of narrative structures reveals that the past and history do not only have an impact on contents, but also on the form of the narrative. Special attention is paid to the way history is told, which turns out to be complex, oscillating between historical objectivity, fantasy, and fiction. The access to history through family romance empha! sizes the memorial aspect of the writing of history. Consequently, personal identity is defined in terms of heritage, both family heritage and historical heritage. In this respect, Patrick Modiano and Monika Maron belong to an entire school of writing, the “generational literature” of the second half of the 20th century.

Pneumonia intersticial familiar (PIF) é definida como a ocorrência de pelo menos dois casos de pneumonia intersticial fibrosante em uma mesma família biológica. Apesar do avanço sobre o tema em anos recentes, ainda não há estudos brasileiros nessa área. O objetivo deste estudo foi caracterizar uma amostra de pacientes brasileiros com PIF quanto aos aspectos clínicos, radiológicos, anatomopatológicos e genéticos, bem como analisar os respectivos comprimentos teloméricos (CT). Entre março de 2014 e novembro de 2017 foi realizada uma busca ativa por casos de PIF. Os pacientes identificados foram submetidos a testes de função pulmonar; tomografia computadorizada de alta resolução (TCAR) de tórax e a coleta de amostras de sangue. Ainda foram realizadas avaliações empregando ficha clínica padronizada. Amostras de tecido pulmonar foram obtidas e revisadas em seis casos. Empregando-se um kit apropriado, DNA genômico foi extraído de células brancas do sangue periférico. A avaliação do CT foi feita pelo método de Southern blot. Um painel envolvendo 154 genes de interesse foi desenvolvido pelo grupo de pesquisa e construído pela empresa Agilent Technologies. A pesquisa desses genes foi realizada empregando-se técnicas de sequenciamento de nova geração (NGS-Illumina). Foram selecionados 35 pacientes, com idade mediana de 66 (35,5-89,3) anos. Tabagismo e outras exposições ambientais estiveram presentes em 45,7% e 80% dos casos, respectivamente. Estertores finos foram identificados em 91,4% dos pacientes e baqueteamento digital em 20%. Os testes de função pulmonar foram classificados como restritivos em 20 (57,1%), normais em 10 (28,6%), inespecíficos em 4 (11,45) e obstrutivo leve em 1 (2,9%). A DCO esteve reduzida nos 30 pacientes em que foi possível pesquisá-la. Padrão típico de PIU na TCAR foi detectado em 6 (17,1%) pacientes e padrão indeterminado para PIU em outros 4 (11,4%). A maioria dos casos, 25 (71,4%), exibiu padrão tomográficoinconsistente com PIU. A revisão do material anatomopatológico revelou pneumonite intersticial com acentuação bronquiolocêntrica em quatro indivíduos. A grande maioria (85,7%) mostrou CTs inferiores ao percentil 50%. Quatro indivíduos exibiram CTs curtos e um muito curto. Foram identificadas variantes genéticas comuns no promotor do gene MUC5B (rs35705950), nos genes TOLLIP (rs111521887, rs5743894 e rs5743890) ou TERT (rs2736100) em 90% dos casos. Detectaram-se ainda sete variantes raras distintas. As alterações c.2594G>A e c.2146G>A do gene TERT, e c.394C>T do gene RTEL1, previamente descritas e associadas a telomeropatias. Uma anormalidade de TERT (c.1730G>A) e outra de RTEL1 (c.2299C>T) inéditas. Duas outras variantes raras encontradas já conhecidas, ainda não haviam sido associadas a doenças pulmonares: gene SHQ1 (c.828_831del) e gene WRAP53 (c.1558dupG). Em conclusão, pacientes brasileiros com PIF demonstram acentuada heterogeneidade fenotípica e genotípica. Este estudo identificou ainda duas novas variantes genéticas raras associadas a PIF e dois possíveis novos genes implicados na patogênese dessa doença. / Familial interstitial pneumonia (FIP) is defined as the occurrence of at least two cases of interstitial fibrosing pneumonias in the same biological family. Despite advances in the field in recent years, there are no Brazilian studies in this area. The aim of this study was to characterize a sample of Brazilian patients with PIF regarding clinical, radiological, histological and genetic aspects, as well as to analyze the respective telomeric lengths (TL). Between March 2014 and November 2017 an active search was conducted for FIP cases. The patients identified were submitted to pulmonary function tests, high resolution computed tomography (HRCT) of the chest and the collection of blood samples. In addition, a standardized clinical file was also fulfilled. Pulmonary tissue samples were obtained and reviewed in six cases. Using a suitable kit, genomic DNA was extracted from white peripheral blood cells. The TL measurements were done by Southern blot method. A panel of 154 genes of interest was developed by the research group and built by Agilent Technologies. Research on these genes was carried out using next generation sequencing techniques (NGSIllumina). Thirty-five patients were selected, with a median age of 66 (35.5-89.3) years. Smoking and other environmental exposures were present in, respectively, 45.7% and 80% of the cases. Fine crackles were identified in 91.4% of patients and digital clubbing in 20%. Pulmonary function tests were classified as restrictive in 20 (57.1%), normal in 10 (28.6%), non-specific in 4 (11.45) and mild obstructive in 1 (2.9%). The DLCO was reduced in the 30 patients in whom it was possible to investigate it. Typical pattern of UIP in HRCT was detected in 6 (17.1%) patients and undetermined pattern for UIP in another 4 (11.4%). The majority of cases, 25 (71.4%), showed a tomographic pattern inconsistent with UIP. The review of histological material revealed interstitial pneumonitis with bronchiolocentric accentuation in four individuals. The vast majority (85.7%) showed TL lower than the 50th percentile. Four individuals had short TL and one a very short TL. Commongenetic variants were identified in the MUC5B gene promoter (rs35705950), in the TOLLIP genes (rs111521887, rs5743894 and rs5743890) or TERT (rs2736100) in 90% of the cases. Seven different rare variants were also detected: the changes c.2594G> A and c.2146G> A of the TERT gene, and c.394C> T of the RTEL1 gene, previously described and associated with telomeropathy; one previously unknown abnormality of TERT (c.1730G> A) and another of RTEL1 (c.2299C> T); two additional rare genetic variants, had not yet been associated with pulmonary diseases: SHQ1 gene (c.828_831del) and WRAP53 gene (c.1558dupG). In conclusion, FIP Brazilian patients demonstrate marked phenotypic and genotypic heterogeneity. This study also identified two new rare genetic variants associated with FIP and two other possible new genes implicated in the pathogenesis of this disease.

Esta pesquisa propõe uma comparação entre contos e romances produzidos por Machado de Assis nas décadas de 1860 e 1870 e produções do teatro realista brasileiro, desenvolvido no país entre as décadas de 1850 e 1860, com o objetivo de capturar suas representações da ordem familiar. Levando-se em conta que Machado de Assis foi entusiasta do realismo teatral, como assinalam alguns dos textos que o autor publicou na imprensa, é possível constatar importantes semelhanças entre a prosa machadiana estudada e obras do teatro realista nacional, no que tange ao tratamento de assuntos concernentes à esfera familiar. De modo geral, esses assuntos têm como eixo o debate sobre a transição de paradigmas familiares por que passava a sociedade brasileira do período, atrelando-se à defesa do casamento eletivo, modelo de união da burguesia então emergente nas cidades, em contraste com o casamento por arranjo familiar, forma de matrimônio típica do universo de relações patriarcais, frequentemente praticada pelas elites locais. Pode-se identificar um complexo estético-ideológico comum às obras de Machado de Assis e às peças mencionadas, marcado pela perspectiva de que a arte teria função didático-moralizante, podendo contribuir para o aprimoramento de instituições sociais como a família e o casamento, sobre as quais esses textos apresentam uma visão positiva. O trabalho separa-se em duas partes. A primeira é dedicada à prosa de Machado de Assis, incluindo os quatro primeiros romances do autor e uma seleção de contos que ele publicou no período correspondente ao recorte cronológico. A segunda parte apresenta a leitura de algumas peças realistas brasileiras, quase todas comentadas por Machado de Assis. Por meio da comparação dessas peças com as obras abarcadas na primeira parte, defende-se a tese de que Machado de Assis incorporou elementos da estética teatral realista para compor a literatura orientada para a vida prática que solicita em alguns de seus contos, e que está sintonizada com os debates sobre a família e as instituições sociais presentes em sua prosa das décadas de 1860 e 1870. / This research establishes a comparison between short stories and novels written by Machado de Assis during the decades of 1860 and 1870, on the one hand, and Brazilian plays pertaining to the theatrical realism, which has been developed in Brazil during the decades of 1850 and 1860, on the other hand. The comparison focuses representations of familial order in those texts. Considering that Machado de Assis was an enthusiast of the theatrical realism, as many of his journalistic texts show, it is possible to identify important similarities between the authors prose and Brazilian realistic plays, in their approach to matters related to familial order. Those texts usually associate these matters with discussions about the changes in the paradigm of family relations in Brazil in the 19th century, standing up for volitional marriage, an ideal of the rising urban bourgeoisie, in contrast to patriarchal arranged marriage, commonly practiced by rural elites. It is possible to recognize an esthetical-ideological structure in both Machado de Assiss prose and realistic plays, characterized by the idea that art had a didactic and moralizing objective, contributing to the development of society institutions such as family and marriage, which these texts present in a positive way. The thesis is divided into two sections. The first one is dedicated to Machado de Assiss prose, including the first four novels written by the author and a selection of the short stories he has published during the selected period. The second one offers an interpretation of some of Brazilian realistic plays, almost all of which were commented by Machado de Assis. From the comparison between these plays and the productions studied at the first section, we argue that Machado de Assis incorporated esthetical elements from theatrical realism, in order to compose a literature directed towards concrete life, which the author stands up for in some of his short stories. This literature, as we shall see, is consistent with the discussions about family and social institutions that are presented in the writers prose in the decades of 1860 and 1870.