Submitted by Maria Dulce (mdulce@ndc.uff.br) on 2014-07-03T16:21:41Z No. of bitstreams: 1 Ferreira, leticia-Tese-2014.pdf: 1380406 bytes, checksum: eb36eb69ce3ec034f5bd593ab75a97a6 (MD5) / Made available in DSpace on 2014-07-03T16:21:41Z (GMT). No. of bitstreams: 1 Ferreira, leticia-Tese-2014.pdf: 1380406 bytes, checksum: eb36eb69ce3ec034f5bd593ab75a97a6 (MD5) Previous issue date: 2014 / A tese tem como objetivo geral investigar a relação entre política fiscal e as ações políticas, privilegiando a dinâmica imposta pela contribuição do donativo para o dote e paz de Holanda nas câmaras de Salvador, Recife, Rio de Janeiro, Lisboa e Porto. Para tanto discute os conceitos de “tributo” e “donativo”, bem como o quadro diplomático no qual o objeto da tese se insere. Analisa processos de negociações e conflitos a partir dos novos estudos sobre história política e fiscal. Procura traçar o perfil dos contribuintes objetivando atestar o caráter geral e proporcional do donativo em questão. Dessa forma entendemos o donativo como um mecanismo utilizado pela coroa e por seus vassalos em um sistema de trocas materiais e simbólicas. / The thesis aims to investigate the relationship between fiscal policy and political actions, focusing on the dynamic imposed by the contribution of the donative for dowry and peace Netherlands in the chambers of Salvador, Recife, Rio de Janeiro, Lisbon and Porto. For both, this work discusses the concepts of “tribute” and “donation” as well as the diplomatic table in which the subject of the thesis for inserts. Analyzes negotiations processes from further studies of political and tax history. Look for plotting the profile of contributors aiming certify the general character and proportion of donation in question. Accordingly we understand the donation as a mechanism used by the crown and the vassals in a system of material and symbolic exchanges.

Abstract Skin stem cells are essential for maintaining epidermal homeostasis by providing new cells to replace those that are lost during normal tissue turnover and repair after injury. Adult epidermal stem cells serve also as the cells of origin for different types of skin cancers. This PhD study investigates the hair follicle (HF) stem cells and skin cancer, and the microenviromental factors that regulate the initiation of tumors and their progression to malignancy. Collagen XVIII is a common basement membrane multidomain proteoglycan highly expressed in HF stem cells (HFSCs) and in malignant skin squamous carcinoma cells. It is known to be essential for the development of the eye, and mutations in the COL18A1 gene cause a rare disease, Knobloch syndrome, with severe eye defects. However, the roles of collagen XVIII in other tissues and diseases are not well understood. Using genetically modified mice, we show here that collagen XVIII is important for the structure and formation of hemidesmosomes, the junctional complexes between epidermal cells and basement membrane. We propose that the disturbed adhesion of the HFSCs to the underlying BM in mice with collagen XVIII ablation leads to defects in stem cell viability and HF cycling. Overexpression of the N-terminal noncollageous sequences of collagen XVIII were sufficient to rescue the abnormal HF phenotype observed in the absence of collagen XVIII. We also found that mice lacking this collagen develop fewer chemical-induced skin tumors, which we suggest is due to increased apoptosis in skin stem cells upon carcinogen-induced DNA damage, and to reduced stemness of tumor cells. In another project we studied the functions of Bmx, a cytoplasmic protein tyrosine kinase, which is upregulated in different types of cancer. However, little is known about the pathways that Bmx regulates in tumors. Therefore, we investigated its roles in cancer using syngeneic tumor assays, and chemical and genetic experimental tumor models. We show here that Bmx promotes tumor growth and progression and induces tumor angiogenesis by contributing to the transduction of VEGF signals. / Tiivistelmä Ihon kantasoluilla on tärkeä tehtävä ihon epidermiksen tasapainon (homeostaasin) ylläpitämisessä. Kantasolut jakautuvat tarvittaessa ja tuottavat uusia erilaistuneita soluja sekä ihon pintasolukon normaalin uusiutumisen että vahingoittuneen kudoksen korjaamisen yhteydessä. Ihon kantasoluilla uskotaan olevan myös tärkeä rooli erilaisten ihosyöpien synnyssä. Tässä tutkimuksessa tutkittiin ihon karvatupen kantasoluja ja ihosyöpää, ja selvitettiin kantasoluja ympäröivän kudoksen, mikroympäristön (kantasolulokero), merkitystä ihosyövän synnyssä ja etenemisessä. Kollageeni XVIII on useista toiminnallisista osista koostuva tyvikalvojen proteoglykaani, joka ilmenee voimakkaasti ihon karvatupen kantasoluissa, sekä ihon pahanlaatuisissa levyepiteelikarsinoomasoluissa. Vaikka kollageeni XVIII:n biologiset tehtävät elimistössä ovat vielä jokseenkin epäselviä, sen tiedetään olevan välttämätön silmän kehittymiselle. Kollageeni XVIII:n geenimutaatioiden on osoitettu aiheuttavan Knoblochin oireyhtymän, jota sairastavilla potilailla on muutoksia silmän rakenteessa. Tässä väitöskirjatyössä hyödynnettiin useita muuntogeenisiä hiirimalleja ja osoitettiin, että kollageeni XVIII säätelee merkittävästi ihon karvatupen erilaistuvien solujen elinkykyä ja karvojen kasvukiertoa. Kollageeni XVIII:n puutos aiheutti muutoksia karvatupen pullistuma-alueen (bulge) liitoskomplekseissa (hemidesmosomi), jotka ankkuroivat alueen tyvisolut karvatuppea ympäröivään tyvikalvoon. Tulokset viittaavat siihen, että puutteelliset liitokset solujen ja tyvikalvon välillä ja niistä johtuvat signaalinvälityksen häiriöt voivat aiheuttaa muutoksia karvatupen solujen ominaisuuksissa. Kollageenin XVIII:n aminoterminaalisen osan tuottaminen poistogeenisen hiiren ihossa riitti palauttamaan hemidesmosomit, karvatupen solujen elinkyvyn ja karvasyklin normaaliksi. Työssä havaittiin myös, että kollageeni XVIII puute vähensi kemikaalikäsittelyillä aiheutettujen ihokasvainten määrää hiirillä, mitä voidaan osaltaan selittää sillä, että kollageeni XVIII:n puutos lisäsi DNA-vaurioista kärsivien erilaistuvien solujen ohjelmoitua solukuolemaa (apoptoosi) ja vähensi kasvainsolujen kantasoluominaisuuksia. Tässä työssä tutkittiin myös monissa syövissä voimakkaasti ilmenevän solunsisäisen signaalinvälittäjän tyrosiinikinaasi Bmx:n tehtäviä syövässä hyödyntäen istutettavia kasvainsoluja sekä kemiallista ja geneettisiä kokeellisia syöpämalleja muuntogeenisillä hiirillä. Tutkimuksessa ositettiin Bmx:n osallistuvan verisuonikasvutekijän signaalinvälitykseen ja täten edistävän syöpäkasvainten verisuonten uudismuodostusta sekä syövän kasvua ja etenemistä.

Abstract Collagen XVIII is a multidomain basement membrane proteoglycan with three tissue-specific isoforms. Endostatin, the C-terminal part of collagen XVIII, has antiangiogenic properties, while the frizzled-like domain of the longest isoform is suggested to be capable of inhibiting the Wnt/β-catenin signaling network. This study utilized several genetically modified mouse lines and electron microscopy to achieve new information on the biological role of collagen XVIII, its different isoforms, and the frizzled domain. Lack of collagen XVIII was found to affect the integrity of basement membranes of various tissues, leading to an abnormally loosened network structure. In the choroid plexus, the change in the basement membrane ultrastructure caused alterations in the production of the cerebrospinal fluid and predisposed to the development of hydrocephalus. In the kidney, broadening of the proximal tubular basement membrane was shown to be due specifically to the lack of the short isoform, while the lack of the two longer isoforms led to podocyte foot process effacement. Moreover, lack of collagen XVIII was found to cause softening of the kidney glomeruli and the levels of serum creatinine were elevated in the mutant animals, indicating altered kidney function. The hair follicle cycle was used as a model to study the possible role of the frizzled domain of collagen XVIII in the Wnt/β-catenin signaling cascade. The longer collagen XVIII isoforms were shown to be expressed in the basement membrane facing the dermal papilla and in the hair follicle bulge, containing the follicular stem cells. Lack of the long isoforms led to abnormalities in the progression of the first hair cycle, and the phenotype could be rescued via transgenic delivery of the frizzled domain of the longest isoform, suggesting its involvement in the regulation of the Wnt/β-catening signaling network during the cyclic growth of the hair. / Tiivistelmä Kollageeni XVIII on useista toiminnallisista osista koostuva tyvikalvojen proteoglykaani, jolla on kolme eri kudoksissa esiintyvää isomuotoa. Sen C-terminaalisella endostatiini-osalla on verisuonten kasvua estäviä vaikutuksia, kun taas pisimmän isomuodon frizzled-osan uskotaan estävän Wnt/β-kateniini signalointireitin toimintaa. Tässä tutkimuksessa saatiin uutta tietoa kollageeni XVIII:n, sen eri isomuotojen sekä frizzled-osan biologisesta merkityksestä useiden geenimuunneltujen hiirimallien sekä elektronimikroskopian avulla. Kollageeni XVIII:n puutoksen todettiin vaikuttavan tyvikalvojen rakenteen eheyteen useissa eri kudoksisssa, johtaen epänormaalisti löyhtyvään verkkorakenteeseen. Suonipunoksessa tämä tyvikalvon hienorakenteen muutos vaikutti aivo-selkäydinnesteen tuottumiseen ja altisti vesipään kehittymiselle. Munuaisessa proksimaalisen munuaistiehyen tyvikalvon levenemisen osoitettiin johtuvan lyhyen isomuodon puutoksesta, kun taas kahden pidemmän isomuodon puuttuminen aiheutti podosyyttien jalkalisäkkeiden leviämistä. Lisäksi kollageeni XVIII:n puuttumisen osoitettiin johtavan hiirimallien munuaiskerästen pehmenemiseen sekä veren kreatiniinitason kohoamiseen, viitaten munuaistoiminnan häiriöihin. Karvatuppien syklistä kasvua käytettiin mallina tutkittaessa kollageeni XVIII:n frizzled-osan mahdollisia vaikutuksia Wnt/β-kateniini signalointireittiin. Pidempien kollageeni XVIII isomuotojen osoitettiin tuottuvan karvanystyn tyvikalvossa sekä karvatupin kantasolut sisältävällä pullistuma-alueella. Pitkien isomuotojen puuttuminen johti karvojen ensimmäisen kasvukierron epänormaaliin etenemiseen. Tämä voitiin estää siirtogeenisen frizzled-osan avulla, mikä viittasi sen osallisuuteen Wnt/β-kateniini signalointireitin säätelyyn karvan syklisen kasvun aikana.

Les protéases Tolloïdes constituent un groupe de métalloprotéases extracellulaires comptant quatre membres chez les mammifères (BMP-1, mTLD, mTLL-1 et mTLL-2). Ces protéases jouent un rôle majeur dans le développement et la réparation tissulaire, ainsi que dans certaines pathologies comme les fibroses. En 2006, le premier inhibiteur endogène des protéases Tolloïdes a été identifié chez le xénope et le poisson zèbre. Il s'agit de la protéine Sizzled, qui appartient à la famille des secreted Frizzled-Related proteins (sFRPs). Le travail présenté dans ce manuscrit suggère que ce mécanisme d'inhibition des protéases Tolloïdes par les sFRPs n'est pas conservé chez les mammifères. En effet, trois des cinq sFRPs de mammifères ont été testées (sFRP1, sFRP2 et sFRP4), et aucune d'entre elles ne s'est avérée capable d'inhiber l'activité de la protéase BMP-1 humaine in vitro. Ce travail montre toutefois que les protéases BMP-1, mTLD et mTLL-1 humaines peuvent être inhibées de façon puissante et spécifique par la protéine Sizzled de xénope. Cette inhibition repose sur l'interaction du domaine Frizzled de Sizzled avec le domaine catalytique des protéases Tolloïdes. Plus particulièrement, les résidus Asp-92, Phe-94, Ser-43 et Glu-44 de Sizzled (dont certains ne sont pas présents chez les sFRPs de mammifères) jouent un rôle crucial dans cette inhibition. Enfin, nous nous sommes intéressés au variant long du collagène XVIII, qui comporte également un domaine Frizzled. Nous avons pu montrer que BMP-1 clive le collagène XVIII in vitro, libérant un fragment contenant le domaine Frizzled. Des expériences sont en cours pour déterminer si ce fragment est capable d'inhiber les protéases Tolloïdes / Tolloid proteinases constitute a group of extracellular metalloproteinases which includes four members in mammals (BMP-1, mTLD, mTLL-1, mTLL-2). These proteinases play major roles in development, tissue repair and related pathological conditions such as fibrosis. In 2006, the first endogenous inhibitor of Tolloid proteinases was identified in Xenopus and zebrafish. This inhibitor, called Sizzled, is a member of the secreted Frizzled- related proteins (sFRPs). The present study strongly suggests that inhibition of Tolloid proteinases activity by sFRPs is not conserved in mammals. Indeed, three of the five mammalian sFRPs were tested (sFRP1, sFRP2 and sFRP4) and none of them was found to inhibit human BMP-1 activity in vitro. In contrast, this study demonstrates that Xenopus Sizzled is a potent and specific inhibitor of human BMP-1, mTLD and mTLL-1. This inhibition involves an interaction between the Frizzled domain of Sizzled and the catalytic domain of Tolloid proteinases. More precisely, residues Asp-92, Phe-94, Ser-43 and Glu-44 of Sizzled (among which only Asp-92 is conserved in mammalian sFRPs) play a crucial role in Tolloid proteinase inhibition. Finally, we studied the longest isoform of collagen XVIII, which also contains a Frizzled domain. We found that BMP-1 can cleave collagen XVIII in vitro, resulting in a Frizzled domain-Containing fragment. Experiments are in progress to determine if this fragment can also inhibit Tolloid proteinase activity

O colágeno XVIII é um componente das membranas basais com diversos domínios funcionais, como a endostatina e o domínio frizzled, que têm importante papel em processos celulares como proliferação e diferenciação. COL18A1 possui dois promotores alternativos: o promotor 1, que regula a síntese da variante NC11-303, e o promotor 2 responsável pelas variantes NC11- 728 e NC11-493, expressas por hepatócitos. Existe uma variação interindividual da endostatina circulante e da expressão do colágeno XVIII no fígado. A expressão do colágeno XVIII/endostatina foi correlacionada com a progressão tanto do hepatocarcinoma (HCC), quanto da fibrose/cirrose hepática. Elucidar a regulação da expressão de COL18A1 pode auxiliar na compreensão dessa variação interindividual e da progressão dessas doenças. Neste trabalho demos início a caracterização do promotor 2 do COL18A1. Identificamos na seqüência predita como promotora cinco regiões conservadas entre humanos e camundongos. A análise in silico e funcional dessas regiões revelou que os fatores de transcrição, Sp1, Sp3, YY1, Oct-1, C/EBPα e C/EBPβ, interagem com as mesmas. Demonstramos que C/EBPβaumenta a taxa de transcrição do promotor 2 em hepatócitos, e que existe uma correlação positiva da expressão de NC11-493 com C/EBPαe C/EBPβem tecido hepático cirrótico e tumoral. As expressões de C/EBPαem tecido hepático cirrótico e tumoral estão diretamente correlacionadas, enquanto que os níveis de NC11-493 nos tumores estão inversamente correlacionados com o tamanho dos mesmos. Mostramos a existência de diversos SNPs no promotor 2. O SNP-700T/G, funcional in vitro, afeta a interação de Sp3 e YY1 com essa região regulatória. A deleção da região do SNP indicou que ela possui elementos importantes para a transcrição em hepatócitos, apesar deste SNP não estar relacionado com o nível de expressão do colágeno XVIII em fígado fibrótico ou com susceptibilidade a HCC. O SNP- 700T/G está em desequilíbrio de ligação com o SNPc.1135C/T, no domínio frizzled do colágeno XVIII. Não foi possível elucidar a funcionalidade do SNPs c.1135C/T in vitro, mas os haplótipos formados por esses dois SNPs têm diferentes frequências entre descendentes de europeus e de africanos. Nosso trabalho traz importantes contribuições e abre novas perspectivas para a compreensão da regulação do colágeno XVIII em fígado humano, tanto em situações fisiológicas, quanto em processos fibrogênicos e tumorigênicos¶ / Collagen XVIII is a basal membrane component with several funcional domains, such as endostatin and frizzled domains, which have important roles in cellular processes such as proliferation and differentiation. COL18A1 has two promoter regions: promoter 1, that regulates the synthesis of NC11-303 isoform, and promoter 2, localized in intron 2, responsible for NC11-728 and NC11-493 isoforms expressed by hepatocytes. There is a large interindividual variation in circulating endostatin and in collagen XVIII liver expression. Collagen XVIII/endostatin levels were correlated with hepatocellular carcinoma (HCC) progression, as well as liver fibrosis/cirrhosis, conditions that precede HCC. Elucidating the mechanisms that regulate COL18A1 expression in hepatocytes may help understanding its variation among individuals and liver disease stages, as well as contribute to new treatment strategies. In this work we began to characterize COL18A1 promoter region 2. We identified in the predicted promoter sequence five conserved regions between human and mouse. The in silico and functional analysis of these regions revealed that transcription factors Sp1, Sp3, YY1, Oct-1, C/EBPα and C/EBPβ interact with them. We have demonstrated that C/EBPβ increases promoter 2 transcription rate in hepatocytes, and that there is a positive correlation of NC11-493 expression with that of C/EBPα and C/EBPβ in cirrhotic and tumor liver samples. Non-tumor and tumor C/EBPα expressions positively correlate between themselves, while NC11-493 tumor expression inversely correlates with tumor size. We also showed that there are several SNPs in COL18A1 promoter 2 region. SNP-700T/G, functional in vitro, affects Sp3 and YY1 interaction with the promoter 2 region and deletion of the SNP region indicated that this sequence has important hepatocyte regulatory elements. Our results suggest that this SNP does not significantly affects COL18A1 expression in fibrotic/cirrhotic liver and is not associated with HCC susceptibility. SNP-700T/G is in linkage disequilibrium with SNPc.1135C/T, at collagen XVIII frizzled domain. We could not elucidate SNPc.1135C/T functionality in vitro, but the haplotypes formed by these two SNPs have different frequencies in European and African descendants. In conclusion, our work brings important contributions and opens new perspectives for the comprehension of collagen XVIII regulation in human liver in physiological situations, as well as in fibrotic/cirrhotic and tumorigenic process.

Las reformas borbónicas han sido vistas tanto como una revolución en la administración virreinal como una “invención historiográfica”. Esta indefinición nace de considerarla como un mensaje impuesto desde arriba, de tal manera que su éxito o fracaso está en directa relación con la voluntad y eficiencia de sus gestores. En línea con recientes investigaciones, este trabajo analizará la práctica política de los actores encargados de las reformas, lo que permitirá observar la complejidad de las articulaciones entre los burócratas y los poderes locales que explican las razones detrás de sus éxitos o fracasos. En ese sentido, esta investigación demostrará que la reforma de policía fracasó porque se vio envuelta en la lucha de poder entre las élites locales y los funcionarios reales que siguió a la instauración del aparato administrativo reformista por los visitadores. Como resultado, todos los implicados quisieron ejercer ese nuevo poder centralizado para sus propios fines. Estos grupos de poder encargados de sostener la reforma, más bien, la utilizaron para su conveniencia al apropiarse de los nuevos poderes que le otorgaba la reglamentación para obtener mercedes y recuperar los privilegios que habían perdido. / The Bourbon reforms have been seen both as a revolution in viceregal administration and as a "historiographical invention." This lack of definition arises from considering it as a message imposed from above, in such a way that its success or failure is directly related to the will of its managers. In line with recent research that qualifies these statements, this research will analyze the political practice of the actors in charge, which will allow to emphasize the complexities and articulations between bureaucrats and local powers to explain the reasons behind their frustration. In this sense, it will be shown that the police reform failed because it was involved in the power struggle between local elites and royal officials that followed the establishment of the reformist administrative apparatus by the visitors. As a result, everyone involved wanted to exercise this new centralized power for their own ends. Rather, these power groups in charge of sustaining the reform used it for their own convenience by appropriating the new powers granted by the regulations to obtain grants and regain the privileges they had lost

La obra satírica de fray Francisco del Castillo es motivo de análisis e investigación, pues su corpus literario suele ser discutido por las distintas observaciones sobre algunos poemas que fueron adjudicados sin una previa corroboración autoral. Es por esta razón que discutimos si la poesía del mercedario es identificada como una producción netamente satírica o comparte características y condiciones textuales propias a la burlesca. Así, señalamos que la obra satírica de Del Castillo debe ser analizada desde una preceptiva satírico burlesca que invite a la reflexión del corpus poético seleccionado. En esta investigación, en primer lugar, establecemos una selección de textos poéticos que nos permitirá debatir las adjudicaciones literarias realizadas por Ricardo Palma a fray Francisco del Castillo, demostraremos que estas designaciones siguieron un interés exclusivo del tradicionalista. En segundo lugar, empleamos la teoría sobre la sátira y géneros festivos literarios para demostrar la interrelación entre este tipo de literatura con un contexto social que se discute y señala como corrupto. Observaremos cómo el mercedario trabajó los temas satíricos y se encuentran circunscritos a los cánones del neoclasicismo literario. Finalmente, revisamos los recursos retóricos y estilísticos que se utilizaron como una muestra de su dominio erudito en el quehacer literario de la sátira. Concluimos con que el mercedario demuestra en sus poemas un uso exclusivo de las leyes que gobiernan a la sátira y géneros festivos empleados, por lo que sugiere al lector una visión más crítica sobre lo que representa.

El interés por la composición social de Hispanoamericana es un tema muy amplio en el que los estudios de la inmigración cobran cada día mayor importancia. Por su parte en las últimas años la exploración de la composición de la República de Españoles aunque con un notable retraso frente a la investigación de la República de Indios, ha realizado un cierto avance. Al interior de este campo, el estudio de las poblaciones extranjeras ocupa un espacio mucho más reducido aunque no por ello desdeñado. / Tesis

En la presente investigación se propone realizar un estudio comparativo del impacto de las reformas borbónicas sobre el conjunto económico de dos regiones determinadas del virreinato, la región del norte y la región del sur andino. Se hará un análisis comparativo de las nuevas instituciones extractivas que se llegan a implementar en las respectivas regiones a fines del siglo XVIII, y se analizará su efecto sobre la producción de metales preciosos y sobre la circulación de mercancías en los espacios regionales. La comparación permitirá identificar si es que las instituciones desarrolladas para el incremento de la producción argentífera crearon un efecto de arrastre en los enclaves mineros, al igual que poder determinar cuál es la diferencia de su impacto en un espacio de actividad minera de más de dos siglos y en otro con actividad minera reciente. Esto podrá demostrarse a través de los registros de Real Aduana de los años 1774 a 1806 que brindan información detallada de las mercancías y su recorrido. / The present paper intends to focus on a comparative study of the impact of the Bourbon reforms on the economies of two particular regions in the viceroyalty of Peru, the northern region and the southern Andean region. I will make a comparative analysis of the new extractive institutions which were implemented in both regions at the end of the eighteenth century, and I will analyze their effect on the production of precious metals and on the circulation of commodities in the regional spaces. The comparison will allow us to identify whether these institutions managed to improve silver production to the point where it could create a pull effect on the sum of the commodities of the region for the supply of its market, it will also let us see the difference of their impact between a region with two centuries of previous silver extraction and one with a more recent mining experience. This will be tested through the Customs records for the years 1774 to 1806 which give information regarding the commodities and their trail.

La presente investigación analiza el proceso de formación del discurso narrativo y visual del indígena peruano y de sus producciones culturales contemporáneas y antiguas durante el periodo borbónico. Es el tiempo del arribo de los viajeros y expedicionarios que gracias al cambio de dinastía en España quedaron habilitados para poder visitar los territorios virreinales y juzgar sus realidades según la nueva mirada científica e imparcial. La construcción del discurso narrativo presenta un tiempo y un recorrido diferente al de la imagen visual. Viajeros y exploradores presentarán en sus novedosos pareceres, prejuicios de antigua data, y será la recolección de información visual, etnológica y arqueológica, así como el esfuerzo por una descruipción más desapasionada y científica la que lleve lentamente y a duras penas a un cambio del discurso narrativo sobre el indígena. Hacia finales del periodo parecieran emparejarse, del mismo modo como el interés por las producciones etnológicas y arqueológicas terminan teniendo un importante desarrollo en el último tercio del periodo escogido. La demarcación cronológica corresponde al período borbónico (1700-1824) y la delimitación espacial abarca el Virreinato del Perú y sus Audiencias sufragáneas. La investigación recogió todos los testimonios disponibles para generar una secuencia de la información y brindar el panorama más completo posible.