INTRODUÇÃO: As mucopolissacaridoses (MPSs) formam um grupo raro de doenças congênitas lisossômicas de depósito, relacionadas a desordens do metabolismo dos glicosaminoglicanos (GAG). Os GAG, parcialmente degradados, acumulam-se nos diversos tecidos do organismo, principalmente das vias aéreas superiores, levando a apneia obstrutiva do sono nesses pacientes. OBJETIVO: Descrever os achados em vias aéreas de pacientes com mucopolissacaridose tipo VI, identificados pela fibronasolaringoscopia (FNL), e compará-los com as alterações na polissonografia (PSG). DELINEAMENTO: Estudo transversal. MÉTODOS: Incluíram-se todos os pacientes com MPS tipo VI, com idade entre 14 e 24 anos, que fazem acompanhamento no Serviço de Genética do Hospital de Clínicas de Porto Alegre. Coletaram-se informações clinico-epidemiológicas dos pais ou responsáveis por meio de entrevista. Realizou-se PSG de noite inteira, classificada em normal, leve, moderada ou gravemente alterada. FNL foi efetuada em consultório, sem sedação, entre 7 dias antes e 7 dias após a PSG. As fibronasolaringoscopias foram gravadas em DVD e analisadas com cegamento para os achados na PSG. A FNL foi classificada em 1- sem obstrução, 2- obstrução leve, 3 - obstrução moderada ou 4 - obstrução grave de vias aéreas, de acordo com o maior escore obtido nas diferentes regiões. RESULTADOS: Avaliaram-se 11 pacientes com MPS tipo VI, sendo 7 (63,6%) do sexo masculino. Na FNL, oito (72,7%) apresentaram obstrução grave, dois (18,2%) obstrução moderada e um (9,1%), obstrução leve de vias aéreas. Na PSG, nove pacientes (81,8%) apresentaram síndrome da apneia obstrutiva do sono (SAOS). Destes, cinco (45,5%) apresentaram SAOS leve, três (27,2%) SAOS moderada e um (9,1%) SAOS grave. Encontrou-se hipertrofia moderada a grave das conchas nasais em 81,8% dos sujeitos e 64% apresentaram obstrução grave em região supraglótica. Não houve associação entre os achados da FNL e da PSG (p=0,454; kappa = - 0,09; IC 95%: - 0,34 a 0,17), demonstrando que não há concordância entre os métodos de avaliação. CONCLUSÃO: A apneia apresenta alta prevalência na amostra e não se correlaciona com o grau de obstrução da via aérea superior. / INTRODUCTION: Mucopolysaccharidosis (MPS) is a lysosomal storage disease that affects an enzyme responsible for the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in several tissues, such as the upper airways, which leads to the development of obstructive sleep apnea (OSA) in these patients. OBJECTIVE: To describe airway findings in mucopolysaccharidosis type VI patients, identified with flexible fiberoptic laryngoscopy (FFL), and compare it with polysomnography (PSG) abnormalities. STUDY DESIGN: Cross-sectional study. METHODS: All MPS VI diagnosed patients, age ranging from 14 to 24 years, followed at the Genetic Division of Hospital de Clinicas de Porto Alegre were included. Clinical and epidemiological data were obtained by an interview with parents. Overnight PSG was performed, and results were classified as normal or mildly, moderately or severely abnormal. FFL was performed at the outpatient clinics, without sedation, between 7 days prior and seven days after PSG. Flexible fiberoptic laryngoscopies were recorded in DVD and analyzed by a blind researcher. FFL was classified as 1 - no obstruction, 2 - mild obstruction, 3 - moderate obstruction or 4 - severe obstruction of the airways, using the highest score obtained in all the regions. RESULTS: Eleven patients with MPS VI were included, and seven (63.6%) were males. Eight (72.7%) had severe obstruction of the airways, two (18.2%) had moderate obstruction, and one (9.1%) had mild obstruction at FFL. At PSG, nine (81.8%) patients had obstructive sleep apnea syndrome (OSAS). Of these, five (45.5%) were mild, three (27.2%) moderate, and one (9.1%) severe OSAS. Moderate to severe hypertrophy of the nasal turbinates was found in 81.8% of the patients, and 64% had severe infiltration of the supraglotic area. There was no association between FFL and PSG findings (p=0.454; kappa= -0.09; CI= -0.34 to 0.17), demonstrating no agreement between the two methods. CONCLUSIONS: In the present study, all patients with MPS showed some degree of airway obstruction. As there was no correlation between FFL and PSG findings, we suggest performing PSG in all subjects with MPS in order to determine disease severity.

INTRODUÇÃO: As mucopolissacaridoses (MPSs) formam um grupo raro de doenças congênitas lisossômicas de depósito, relacionadas a desordens do metabolismo dos glicosaminoglicanos (GAG). Os GAG, parcialmente degradados, acumulam-se nos diversos tecidos do organismo, principalmente das vias aéreas superiores, levando a apneia obstrutiva do sono nesses pacientes. OBJETIVO: Descrever os achados em vias aéreas de pacientes com mucopolissacaridose tipo VI, identificados pela fibronasolaringoscopia (FNL), e compará-los com as alterações na polissonografia (PSG). DELINEAMENTO: Estudo transversal. MÉTODOS: Incluíram-se todos os pacientes com MPS tipo VI, com idade entre 14 e 24 anos, que fazem acompanhamento no Serviço de Genética do Hospital de Clínicas de Porto Alegre. Coletaram-se informações clinico-epidemiológicas dos pais ou responsáveis por meio de entrevista. Realizou-se PSG de noite inteira, classificada em normal, leve, moderada ou gravemente alterada. FNL foi efetuada em consultório, sem sedação, entre 7 dias antes e 7 dias após a PSG. As fibronasolaringoscopias foram gravadas em DVD e analisadas com cegamento para os achados na PSG. A FNL foi classificada em 1- sem obstrução, 2- obstrução leve, 3 - obstrução moderada ou 4 - obstrução grave de vias aéreas, de acordo com o maior escore obtido nas diferentes regiões. RESULTADOS: Avaliaram-se 11 pacientes com MPS tipo VI, sendo 7 (63,6%) do sexo masculino. Na FNL, oito (72,7%) apresentaram obstrução grave, dois (18,2%) obstrução moderada e um (9,1%), obstrução leve de vias aéreas. Na PSG, nove pacientes (81,8%) apresentaram síndrome da apneia obstrutiva do sono (SAOS). Destes, cinco (45,5%) apresentaram SAOS leve, três (27,2%) SAOS moderada e um (9,1%) SAOS grave. Encontrou-se hipertrofia moderada a grave das conchas nasais em 81,8% dos sujeitos e 64% apresentaram obstrução grave em região supraglótica. Não houve associação entre os achados da FNL e da PSG (p=0,454; kappa = - 0,09; IC 95%: - 0,34 a 0,17), demonstrando que não há concordância entre os métodos de avaliação. CONCLUSÃO: A apneia apresenta alta prevalência na amostra e não se correlaciona com o grau de obstrução da via aérea superior. / INTRODUCTION: Mucopolysaccharidosis (MPS) is a lysosomal storage disease that affects an enzyme responsible for the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in several tissues, such as the upper airways, which leads to the development of obstructive sleep apnea (OSA) in these patients. OBJECTIVE: To describe airway findings in mucopolysaccharidosis type VI patients, identified with flexible fiberoptic laryngoscopy (FFL), and compare it with polysomnography (PSG) abnormalities. STUDY DESIGN: Cross-sectional study. METHODS: All MPS VI diagnosed patients, age ranging from 14 to 24 years, followed at the Genetic Division of Hospital de Clinicas de Porto Alegre were included. Clinical and epidemiological data were obtained by an interview with parents. Overnight PSG was performed, and results were classified as normal or mildly, moderately or severely abnormal. FFL was performed at the outpatient clinics, without sedation, between 7 days prior and seven days after PSG. Flexible fiberoptic laryngoscopies were recorded in DVD and analyzed by a blind researcher. FFL was classified as 1 - no obstruction, 2 - mild obstruction, 3 - moderate obstruction or 4 - severe obstruction of the airways, using the highest score obtained in all the regions. RESULTS: Eleven patients with MPS VI were included, and seven (63.6%) were males. Eight (72.7%) had severe obstruction of the airways, two (18.2%) had moderate obstruction, and one (9.1%) had mild obstruction at FFL. At PSG, nine (81.8%) patients had obstructive sleep apnea syndrome (OSAS). Of these, five (45.5%) were mild, three (27.2%) moderate, and one (9.1%) severe OSAS. Moderate to severe hypertrophy of the nasal turbinates was found in 81.8% of the patients, and 64% had severe infiltration of the supraglotic area. There was no association between FFL and PSG findings (p=0.454; kappa= -0.09; CI= -0.34 to 0.17), demonstrating no agreement between the two methods. CONCLUSIONS: In the present study, all patients with MPS showed some degree of airway obstruction. As there was no correlation between FFL and PSG findings, we suggest performing PSG in all subjects with MPS in order to determine disease severity.

Orientadores: Wanderley Dias da Silveira, Eliana Guedes Stehling / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-17T23:32:04Z (GMT). No. of bitstreams: 1 Pace_Fernandade_D.pdf: 4667016 bytes, checksum: c841e6b899f0efc5569c9c6c6ce46935 (MD5) Previous issue date: 2011 / Resumo: Linhagens de Escherichia coli patogênica para aves (APEC) causam infecções extraintestinais e são responsáveis por significativas perdas econômicas na indústria avícola mundial. Recentemente, foram descritos isolados de APEC geneticamente relacionados a diversas outras E.coli extraintestinais (ExPEC) de origem humana, indicando a possibilidade das mesmas constituírem risco zoonótico para humanos. Alguns dos conhecidos fatores de virulência de APEC incluem adesinas, sistema de aquisição de ferro, citotoxinas, entre outros. Nesse trabalho, demonstramos que a linhagem de APEC SEPT 362, isolada do fígado de uma ave apresentando sinais clínicos de septicemia, expressa o Sistema de Secreção Tipo VI (SST6), causa rearranjo do citoesqueleto de células epiteliais cultivadas in vitro, é capaz de aderir e invadir células HeLa e é viável dentro de macrófagos. Para estudar o envolvimento do SST6 na patogênese da linhagem SEPT362, foram deletados três genes desse sistema: hcp, que codifica para uma proteína estrutural e secretada, clpV, que codifica para uma ATPase e icmF (intracellular multiplication factor), gerando três mutantes, respectivamente. Todos os mutantes demonstraram uma diminuição nos processos de adesão e invasão a células HeLa, formação de biofilme e virulência in vivo. Estudos de transcriptoma mostraram que a expressão da fímbria tipo 1 encontra-se diminuída nesses mutantes, o que poderia ser responsável pela diminuição do processo de adesão e invasão às células epiteliais. Nesse trabalho, demonstramos que o SST6 é importante para o processo de patogenicidade, visto que todos os mutantes tiveram sua virulência atenuada em experimentos realizados in vivo com uma significativa diminuição de características relacionadas à patogenicidade in vitro. Esses resultados demonstram que os genes estudados do SST6 influenciam a expressão da fímbria tipo 1 e contribuem para a patogênese desta linhagem APEC / Abstract: Avian pathogenic Escherichia coli (APEC) strains frequently cause extraintestinal infections and are responsible for significant economic losses in the poultry industry worldwide. APEC isolates are closely related to human extraintestinal pathogenic E. coli (ExPEC) strains and may also act as pathogens for humans. Known APEC virulence factors include adhesins such as type 1 fimbriae and curli, iron acquisition systems, and cytotoxins, among others. Here we demonstrated that APEC strain SEPT362, isolated from a septicemic hen, expresses a type VI secretion system (T6SS), causes cytoskeleton rearrangements, invades epithelial cells, replicates within macrophages, and causes lethal disease in chicks. To assess the contribution of the T6SS to SEPT362 pathogenesis, we generated three mutants, ?hcp (which encodes a protein suggessed to be both secreted and a structural component of the T6SS), ?clpV (encoding the T6SS ATPase) and ?icmF (intracellular multiplication factor). All mutants showed decreased adherence and invasion to HeLa cells and decrease in several other pathogenicity related characteristics. Transcriptome studies showed that the level of expression of type 1 fimbriae was decreased in these mutants, which may account for the diminished adhesion and invasion of epithelial cells. The T6SS seems to be important for the disease process, given that both mutants (?hcp and ?clpV) were attenuated in an infection model in chicks. These results suggest that the T6SS influences the expression of type 1 fimbriae and contributes to the pathogenesis of this APEC strain pathogenesis / Doutorado / Genetica de Microorganismos / Doutor em Genetica e Biologia Molecular

É expressiva no espaço urbano brasileiro a presença de um grande número de moradores vivendo em situação de risco e vulnerabilidade social. Isso é visível diante da precariedade de suas moradias, da infraestrutura dos bairros, da condição socioeconômica entre outros fatores, chamando a atenção para a rapidez com que essas moradias favelas - se proliferaram na cidade de Londrina. Diante deste contexto, esta tese tem como objetivo desenvolver um estudo centrado nas reflexões sobre o pertencimento ao lugar favela por parte dos moradores do Jardim União da Vitória VI, localizado na zona sul da cidade de Londrina, bem como analisar a temática sobre o termo lugar e do conceito de favela. Além disso, averiguar sua percepção por um grupo de pessoas, e alunos do 7ºano de duas escolas públicas localizadas na área de estudo ou próxima, e as intervenções do poder público local na elaboração e implantação de politicas públicas, levando em conta a questão habitacional e o contexto histórico da formação da cidade de Londrina. / It is expressive in the Brazilian urban area the presence of a great number of dweller living in a risk situation and social vulnerability. It is visible before preciosity of their dwellings, the districts infrastructure, social-economic condition among other factors, calling the attention to rapidity with which theses dwellings shanty town, proliferate in Londrina city. Ahead this context, this thesis has as objective develops a center study in the reflection about the belonging to the shanty town place by its dwellers of Victory Union Garden VI, situated in the South Zone of Londrina city, as well as to analyze the theme about place term and the concept of shanty town. Beyond that, ascertain its perception by a group of people, and pupils of 7º year of two public schools situated in the study area or close to it, and the local Public Authority interventions in elaboration and implementation of public politics, taking in account the housing issue and the historical context of the formation of Londrina city.

Les Adénovirus humains sont des virus non enveloppés se répliquant dans le noyau des cellules hôtes.Durant l’infection et après leur entrée par endocytose, les Adénovirus sont transportés au noyau pourinitier l’expression du génome viral. Dans l’endosome, les capsides virales subissent un désassemblagepartiel et libèrent le facteur viral lytique, la protéine VI (pVI). Au niveau de la membrane de l’endosome,cette protéine va alors induire sa rupture permettant ainsi le relargage des virions au sein du cytoplasmegrâce à son hélice amphipatique N-terminale. Par la suite, pVI est transportée vers des structuresnucléaires appelées PML nuclear bodies (PML-NB), associée une ubiquitine ligase cytoplasmique, laNedd4.2. Les PML-NB sont des complexes nucléaires multi-protéiques qui ont des propriétésantivirales. Celles-ci impliquent le recrutement de facteurs de transcription répressifs comme parexemple la protéine anti apoptotique Daxx ou encore le suppresseur de tumeur p53, impliqué dans larégulation du cycle cellulaire. Il a été montré que la protéine pVI en complexe avec Nedd4.2 induit larelocalisation de Daxx des PML-NB dans le cytoplasme, ce qui permet une expression efficace dugénome viral. Ainsi, l’inhibition fonctionnelle de Daxx par pVI suggère que cette protéine virale puisseaussi être impliquée dans la restriction de p53.Dans cette étude, nous avons montré que le nombre des modifications post-traductionnelles (PTM) dep53 augmentent en présence de pVI dans la cellule. De plus, les données obtenues montrent quel’expression de pVI affecte la transcription dépendante de p53 et que l’interaction avec Nedd4.2 n’estpas nécessaire pour inhiber les fonctions de p53. Pour étudier l’implication de pVI dans la modulationdu cycle cellulaire, nous avons créé une lignée cellulaire humaine exprimant cette protéine virale defaçon stable. La caractérisation de cette lignée a permis de mettre en évidence une prolifération cellulaireaccrue. Nos observations ont aussi montré une perte importante des PML-NB et une réduction desprotéines clés du cycle cellulaire p53 et pRb, un autre suppresseur de tumeur. Par des techniques demicro-injection et l’utilisation de l’inhibiteur MG132, nous avons observé que ces deux facteurscellulaires sont ciblés vers le protéasome et dégradés lors de la surexpression de pVI. L’étude desfonctions de cette protéine virale laisse penser que la protéine pVI présente un potentiel oncogéniquecar en effet, sa surexpression induit la dérégulation de l’homéostasie cellulaire et l’inhibition desuppresseurs de tumeur, comme p53 et pRb. / Human Adenovirus are non-enveloped viruses which replicate inside the host cell nucleus. Uponinfection and after receptor-mediated entry, they are transported towards the nucleus to initiate the viralgene expression. Viral capsids deliver from the endosome into the cytoplasm by partial disassembly andrelease inside the endosome mediated by viral lytic factor protein VI (pVI). pVI is targeted to themembrane via an amphipathic helix structure in the N-terminus of the viral protein. After membranerupture and capsid release, pVI is transported to sub-nuclear structures, so-called PML nuclear bodies(PML-NBs), together with the cytoplasmic ubiquitin ligase Nedd4.2. PML-NBs represent multiproteinaggregates in the host-cell nucleus with an antiviral capacity, as to several PML-associated repressivetranscription factors, such as the anti-apoptotic Daxx protein and the tumor suppressor p53 were reportedto localize at these foci. In addition, pVI-mediated displacement of Daxx from PML-NBs was shown tooccur in dependency of Nedd4.2 to support efficient viral gene expression. Therefore, we postulate thatbesides Daxx functional inhibition, pVI might also be involved in p53 restriction.Here, we show that p53 posttranslational modification (PTM) is increased when pVI protein is presentin the host-cell. Moreover, we obtained data that pVI expression severely impacts p53 inducedtransactivation of cellular transcription. Biochemical approaches indicate that pVI binding of theubiquitin ligase Nedd4.2 is no prerequisite for the capacity to inhibit p53 functions. In a next step toelucidate the role of pVI on cell cycle regulation, we generated a human cell line stably expressing theviral pVI protein. Our characterization analyses show significantly that these cells benefit from thepresence of pVI as we proved increased cell proliferation rates. We also observed an intense loss ofPML-NBs and reduced protein concentrations of cycle key regulators p53 and pRb. Usingmicroinjection and the inhibitor MG132 we were able to show that both cellular restriction factors weresequestered into the proteasomal degradation pathway of the cell. Evaluation of pVI functions temptedus to speculate, whether pVI might execute oncogenic potential upon overexpression, due toderegulation of host-cell homeostasis and inhibition of tumor suppressive determinants. / Humane Adenoviren (HAdV) sind unbehüllte Doppelstrang-DNA-Viren mit einem Proteinkapsid, diesich im Wirtzellkern replizieren. Der lytische Infektionsverlauf beginnt mit dem rezeptor-vermitteltenEintritt des Viruspartikels und dem gerichteten Transport des viralen Genoms zum Wirszellkern. Dasvirale Protein VI (pVI) ist nötig um den effizienten Austritt des bereits disassemblierten Viruspartikelsaus dem zellulären Endosom zu gewährleisten. Durch eine amphipathische Helix im N-terminalenProteinbereich interkaliert dieser lytische Faktor in die endosomale Membran und führt zum Aufbruchdes zellulären Organells. pVI wird anschließend an zelluläre Kernstrukturen, sogenannte PML nuclearbodies (PML-NBs) lokalisiert und komplexiert dort mit der zytoplasmatischen Ubiquitinligase Nedd4.2.PML-NBs stellen nukleäre Multiproteinkomplexe dar, die mittlerweile aufgrund ihrer antiviralenEigenschaften in den Mittelpunkt der virologischen Forschung gerückt sind. Diese zellulären Aggregatebestehen hauptsächlich aus repressiven Transkriptionsfaktoren, wie dem anti-apoptotischen DaxxProtein sowie dem Tumosupressor p53. In diesem Zusammenhang konnte bereits eine pVI-vermittelteRelokalisation des Daxx Proteins aus den PML-NBs gezeigt und als Vorraussetzung zur effizientenVirusgenexpression bestätigt werden. Es stellte sich im Rahmen der vorliegenden Arbeit die Frage, obneben der pVI-abhängigen Daxx Inhibition, auch p53 ein Zielprotein des viralen Capsidproteinsdarstellt.Unsere Arbeiten zeigen erstmals, dass nach der pVI Expression vermehrt posttranslationaleModifikationen am p53 Protein beobachtet werden. Weitere Befunde konnten außerdem einen Einflussvon pVI auf die p53-abhängige Transaktivierung zellulärer Promotoren beweisen. Mittelsbiochemischer Analysemethoden konnten wir zeigen, dass die Kooperation zwischen pVI und Nedd4.2keine Rolle bei der p53 Inhibition zu spielen scheint. Um im nächsten Schritt die Rolle von pVI imZellzyklus genau zu beleuchten, wurde zunächst ein zell-basiertes Modelsystem mit stabilerÜberexpression des viralen Faktors generiert, Anschließende phenotypische Analysen konnten zeigen,dass die Anwesenheit von pVI zur Steigerung der Zellproliferationsrate führt. Im Rahmen unsererUntersuchungen konnten wir auch einen signifikanten Verlust zellulärer PML-NBs beobachten sowieeine Reduktion der p53 und pRb Proteinkonzentration nachweisen. Mittels unter Verwendung vonMikroinjektion und dem Inhibitor MG132 war es uns möglich zu zeigen, dass pVI den proteasomalenProteinabbau der beiden Wirtszelldeterminaten p53 und pRb induziert. Deswegen kann man basierendauf den erhobenen Befunden zur pVI vermittelten Dysregulierung des zellulären Wachstums einonkogenens Potenzial des viralen Faktors annehmen.

Årligen ges ett antal familjetidningar ut i Sverige som på ett eller annat sätt medverkar till att forma den bild av familj som finns i just Sverige. Syftet med undersökningen är att analysera hur familjetidningarna Vi Föräldrar och Mama porträtterar familjer genom sina texter och fotografier. Syftet är vidare även att undersöka hur allomfattande familjetidningarna är gällande olika former av familjekonstellationer. Undersökningen vänder sig till respektive familjetidnings utgåvor som publicerats under år 2020, och dessa har hittats genom den digitala prenumerationstjänsten ARCY. Familjetidningarna har analyserats genom en kritisk diskursanalys, där analysen utgår från Norman Faircloughs tredimensionella modell som innefattar dimensionerna text, diskursiv praktik samt social praktik. Resultatet som framkommer ur den kritiska diskursanalysen påvisar hur det föreligger en tydlig bild kring hur en familj ser ut utifrån Vi Föräldrar och Mama. Likaså påvisar resultatet att tvåsamhetsnormen lyser starkt med sin närvaro, precis som också heteronormen gör i de undersökta familjetidningarna. / Every year, a number of family magazines are published in Sweden that in one way or another contribute to shaping the image of family that exist in Sweden. The purpose of this study is to analyze how the family magazines Vi Föräldrar and Mama portray families through their texts and photographs. The purpose is also to analyze how comprehensive the family magazines are regarding various forms of family constellations. The material in the analysis consists of each family magazine's editions published in 2020 and these have been found through the digital subscription service ARCY. The family magazines have been analyzed through a critical discourse analysis, where the analysis is based on Norman Fairclough's three-dimensional model, which includes the dimensions text, discursive practice and social practice. The results that emerge from the critical discourse analysis show that there is a clear picture of what a family looks like based on Vi Föräldrar and Mama. The result also shows that the norm of duality and the heteronorm is overrepresented in the examined family magazines. / <p>2021-06-02</p>

京都大学 / 新制・課程博士 / 博士(文学) / 甲第25035号 / 文博第940号 / 新制||文||740(附属図書館) / 京都大学大学院文学研究科文献文化学専攻 / (主査)教授 横地 優子, 教授 VASUDEVASomdev, 教授 宮崎 泉 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Biblical and Ancient Studies / M. Th. (Old Testament)

Syftet med denna studie är att med hjälp av kvalitativ metod få en förståelse till vilka strategier invandrare väljer att använda sig utav för att etablera sitt liv i ett nytt land. Frågeställningarna i denna studie är: Hur upplevs förändringsprocessen från flyktingskap till etablering i ett nytt samhälle? Vilka utmaningar upplever människor i dessa processer?

The 'cities of the Levites' have left no trace in the historical and prophetical literature of Israel; they appear only in P and Chronicles. They must then be either a fiction of the later compilers of the Law, or an earlier institution which made no great impact in monarchic times. This study therefore begins with a review of the materials of Levite history up to the Exile; the Levite cities must find a place somewhere within this setting, if they ever had any real existence. In the second chapter we turn to survey the development of modern critical study of Joshua and Chronicles, culminating in the classic interpretations of Wellhausen and, for Chronicles, of Rothstein and Rudolph. These provide the presuppositions widely accepted by more recent scholars. We then examine and compare the texts of the two versions of the Levite city list, from a literary standpoint, and conclude that, contrary to previous opinion, the one in Chronicles represents an earlier stage in the development of the tradition than that in Joshua. There are signs that at some time the list has been remoulded, with additions and deletions, to fit the pattern of four cities from each of the twelve tribes. Having recognised the difficulties in supposing the list to be entirely a late invention, in the second half of this study we try to find the Levite cities' place in history. First, the findings of archaeologists, traditio-historians and form-critics are examined, When their proposals appear not wholly satisfactory, we turn in chapter five to those who have attempted to re-appraise the character of the 'Levites' of these contexts. In pursuing this enquiry further, we reach the conclusion that these 'Levites' must be distinct both from the old secular tribe of Levi, and from the sacerdotal Levites of the Deuteronomic and Priestly literature. The 'cities of the Levites' seem to be towns which, in the second millennium, entered Israel by alliance rather than by conquest. Finally, we observe the measure of correspondence between the areas of 'Levite' and Hivite/Hurrian occupation, and raise the question whether the term 'Levite' here may not stem from a textual corruption of 'Hivite' in the Jerusalem archives.