Taking off from a security related interest in de-democratization processes throughout Europe and the limited theoretical field thereof, this paper examines the political development in Poland 2008-2018. Through a comparison of the development in Poland and Hungary, the ambition is to identify what differs the de-democratization process of the two East European countries in regards to their communist past and in a broader sense to their current membership in the European Union. To guide the comparison is the theoretical framework of Merkel (2004), through both qualitative and quantitative analysis as it has been applied on Hungary by Bogaards (2018). The combined framework provides five categories of defect democracies: exclusive, illiberal, delegative, tutelary and diffusely defect. While Bogaards (2018) categorizes Hungary as a diffusely defect democracy, the study finds that Poland does not adhere to any single one of the categories. The question of what differs the development in Poland and Hungary is best answered in terms of legality. Whereas the systematic Hungarian process has been carried out within legal frames of the majority rule in parliament, the hasty Polish process resembles a palace revolution, as the leading party is interfering with and partly controlling the rule of law. The study provides support to the observations of the EU being an externally limiting, enabling and legitimizing factor of autocratic developments in member states, made by Bozóki and Hegedüs (2018). Additionally, a reverse snowball effect is being put to action by Poland and Hungary vetoing on EU sanctions against one another. The findings of the paper also support observation made of a limited research field; theoretical understanding and international measurement indexes of democratization being insufficient in explaining and describing the emerging de-democratization. The study opens up for further research regarding democratic peace in Europe.

Les chromosomes marqueurs surnuméraires (CMS) sont définis comme des chromosomes de structure anormale qui ne peuvent pas être identifiés ni caractérisés de façon non ambigüe par les techniques de cytogénétique conventionnelle seules et qui sont de taille égale ou plus petits qu’un chromosome 20 de la même métaphase. La prévalence de cette anomalie chromosomique est estimée à 0,071% en post-natal, 0,075% en diagnostic prénatal et 0,288% chez les patients atteints de retard mental et/ou du développement. Chez les patients infertiles, la fréquence des CMS est estimée à 0,122% et varie selon le sexe. Les CMS sont sans conséquence clinique dans 70% des cas. Dans un tiers des cas, ils peuvent être responsables de nombreuses anomalies du développement et de la reproduction humaine. A ce jour, il existe très peu d’études de caractérisation des CMS permettant une cartographie précise des gènes présents. Dans ce travail, nous avons étudié une série de huit CMS par cytogénétique conventionnelle, FISH (fluorescent in situ hybridization) et CGH array (array comparative genomic hybridization). Nous avons établi une cartographie des gènes présents dans ces CMS. L’étude de la relation génotype-phénotype des patients nous a permis de proposer l’implication de certains gènes candidats dans des anomalies du développement et de la reproduction humaine. Notre étude de l’implication des CMS dans les anomalies du développement humain s’est basée sur l’étude cytogénétique de trois fœtus. Les deux premiers fœtus étaient porteurs d’un CMS(20) en anneau. Le sujet 1 présentait un retard de croissance intra-utérin (RCIU) et une dysmorphie cranio-faciale. Le sujet 2 n’avait pas d’anomalies particulières à part une obésité diagnostiquée à l’âge de quatre mois. La taille de ces CMS(20) était de 13,6 Mb pour le sujet 1 et 4,8 Mb pour le sujet 2. Le gène SSTR4 présent sur le CMS(20) du sujet 2 code pour un récepteur de la somatostatine. Cette hormone joue un rôle dans le comportement alimentaire. Le troisième fœtus présentait un hygroma kystique et un RCIU associé à un CMS(13) néocentromérique. Les explorations par CGH array ont révélé un gain chromosomique de la région 13q21.1qter de 39 Mb contenant 80 gènes dont GPC5, GPC6, SPRY2, EFNB2, SOX1 et DZIP1. La modification d’expression de ces gènes est susceptible d’être responsable du phénotype des sujets étudiés.Notre étude de l’implication des CMS dans les anomalies de la reproduction humaine s’est basée sur l’étude cytogénétique de cinq patients qui présentaient des troubles de la fertilité (anomalies de la spermatogenèse, insuffisance ovarienne prématurée, syndrome des ovaires polykystiques et fausses couches spontanées). Les CMS explorés par CGH array correspondaient aux régions chromosomiques 15q11.2 (3,6 Mb), 21p11.2 (0,266 Mb), 6p11.2q12 (9 Mb) et 20p11.21 (3,3 Mb). Le CMS d’une des patientes ne contenait pas d’euchromatine et une autre patiente était porteuse de deux CMS d’origines chromosomiques différentes. Plusieurs gènes candidats (POTE B, BAGE et THBD) ont pu être identifiés. La modification de leur expression ainsi que des effets mécaniques ou biochimiques perturbant la méiose et la maturation des gamètes pourraient être responsables des troubles de la fertilité observés chez ces patients. L’étude des CMS par CGH array nous a permis de caractériser précisément les points de cassure des CMS, leur taille et leur composition génétique afin de cartographier les gènes présents dans les CMS et d’établir des relations entre le génotype et le phénotype des patients. / Small supernumerary marker chromosomes (sSMC) are defined as structurally abnormal chromosomes which cannot be unambiguously identified or characterized by conventional banding cytogenetic techniques alone and are generally equal in size or smaller than a chromosome 20 of the same metaphase spread. sSMC frequency is estimated at 0.071% in postnatal cases, 0.075% in prenatal cases, and 0.288% for mentally and/or development retarded patients. In infertile patients cases, sSMC frequency is estimated at 0.122% and is different in male (0.165%) and female infertility (0.022%). sSMC have no clinical consequences in 70% of the cases. In one third of the cases, they can be responsible for various human development and reproduction anomalies. To date, only a few studies precisely characterizing the sSMC contents have been performed.In this study, we used conventional cytogenetics, FISH (fluorescent in situ hybridization) and array CGH (array comparative genomic hybridization) to characterize eight sSMC and to precisely localize the genes included. The study of the genotype-phenotype correlations of the patients led us to suppose the implication of some candidate genes in human development and reproduction anomalies.Our study of the implication of sSMC in human development anomalies was based on the cytogenetic study of three fetuses. The first two fetuses carried a ring sSMC(20). Case 1 presented with intrauterine growth retardation and craniofacial dysmorphism. Case 2 had a normal phenotype except for obesity diagnosed at the age of four months. The size of these sSMC(20) was approximately 13,6 Mb for case 1 and 4,8 Mb for case 2. The SSTR4 gene located on the case 2 sSMC(20) is coding for one of the somatostatin receptor. This hormone has multiple effects on variable cells and is implicated in the regulation of food behavior, which could explain the obesity of case 2. Case 3 presented with intrauterine growth retardation and a cystic hygroma associated with a neocentric sSMC(13). Array CGH investigations showed a 32.9 Mb gain from 13q31.1 to 13qter region containing 80 genes. Among these genes, six genes could be involved in the phenotype of the proband (GPC5, GPC6, SPRY2, EFNB2, SOX1 and DZIP1). The expression modification of these genes could be responsible for the phenotype observed.Our study of the implication of sSMC in human reproduction anomalies was based on the cytogenetic study of five patients presenting fertility troubles (spermatogenesis impairment, ovarian insufficiency, polycystic ovary syndrome and repeated abortions). The sSMC explored by array CGH corresponded to the 15q11.2 region (3.6 Mb), the 21p11.2 region (0.266 Mb), the 6p11.2q12 region (9 Mb) and 20p11.21 region (3.3 Mb). The sSMC of one of the patients did not contain euchromatin and one patient carried two sSMC derived from two different chromosomes. Among the genes present on the sSMC, some candidate genes (POTE B, BAGE and THBD) have been identified. The modification of their expression and mechanical or biochemical effects of the sSMC impeding meiosis could be directly responsible for the fertility trouble observed in these patients. A detailed molecular cytogenetic investigation using array CGH allowed us to precisely characterize the chromosomal breakpoints, the size and genomic constitution of sSMC. This study may be helpful to address genotype–phenotype correlations and for medical and genetic counseling.

O basidiomiceto Crinipellis perniciosa (Stahel) Singer (Tricholomataceae), é um parasita hemibiotrófico causador da doença Vassoura-de-Bruxa do cacaueiro (Theobroma cacao) . Os sintomas da vassoura incluem o excesso de brotações em ramos e almofadas florais, abortamento de flores e frutos novos e formação de manchas necróticas nos frutos em maturação. Causando perda na produção. Para a identificação de genes diferencialmente expressos no hospedeiro, no período assintomático, duas bibliotecas subtrativas foram construídas confrontando o genótipo suscetível ‘ICS 39’ e o resistente ‘CAB 214’, inoculados. Uma análise detalhada de 23 genes por PCR quantitativo revelou diferenças na cinética da indução no período assintomático. A indução dos genes no genótipo suscetível em resposta ao C. perniciosa foi atrasada e reduzida, e no resistente houve uma indução mais rápida e intensa, com dois momentos de indução (24 e 120 horas após inoculação). Os genes e mecanismos de patogenicidade Crinipellis perniciosa são amplamente desconhecidos. Genes presumíveis de patogenicidade de Crinipellis perniciosa foram identificados em uma biblioteca enriquecida por hibridização subtrativa supressiva para genes induzidos sob baixa disponibilidade de Nitrogênio. Oito genes foram avaliados para expressão in vitro e em plantas inoculadas por amplificação quantitativa de transcritos reversos (RT-qPCR) e, dos sete expressos diferencialmente sob a carência de N, seis foram induzidos durante os períodos assintomáticos, corroborando a hipótese de convergência na via de sinalização para estresse nutricional abiótico e a patogênese. / The basidiomycete Crinipellis perniciosa (Stahel) Singer (Tricholomataceae) is the causal agent of witches' broom disease in Theobroma cacao (cacao). The hemibiotrophic pathogen infects meristematic tissues (shoots, flower cushions, single flowers and developing fruits). Hypertrophic growth of infected buds (?brooms?) is the most dramatic symptoms, but economic losses result from pod infection. To identify genes differentially expressed in the host during the symptomless stage, two subtractive suppressive libraries were constructed, subtracting in both directions transcripts from the inoculated susceptible genotype ‘ICS 39’ and from the resistant ‘CAB 214’. Quantitative reverse transcription amplification (RT-qPCR) of 23 genes identified as differentially expressed revealed distinct kinetics of gene induction at the asymptomatic stage. Expression induction in the susceptible genotype in response to C. perniciosa was delayed and limited, while in the resistant, there was a quicker and more intense reaction, with two peaks of gene induction at 48 and 120 h after inoculation.. Pathogenicity genes and mechanisms of Crinipellis perniciosa are laregly unknown.. Putative pathogenicity genes from Crinipellis perniciosa were identified in a cDNA library enriched by subtractive suppressive hybridization for genes induced under limiting Nitrogen. The eight genes were analysed for expression by quantitative amplification of reversed transcripts (RT-qPCR) in vitro and inoculated plants, and from the seven differentially expressed under N deprivation, six were induced under the symptomless stage of the disease, corroborating the hypothesis of convergence between the signal pathway for nutritional stress and pathogeneis.

A odontologia reabilitadora moderna preconiza cada vez mais o uso de implantes dentais para a substituição de dentes ausentes. É sabido que micro-organismos presentes na cavidade oral, em especial os relacionados à doença periodontal, são responsáveis pelos maiores índices de insucesso dos implantes. Este trabalho estudou a ocorrência de infiltração bacteriana através da interface implante-conector protético de implantes Cone Morse (CM) e Hexágono Interno (HI) após a associação com uma pasta antimicrobiana ou a adição de sais de prata nos pilares. Foram utilizados 72 implantes odontológicos de titânio (PROSS® - Sistema de Implantes, Dabi-Atlante, Ribeirão Preto, Brasil), 36 com conexão do tipo hexágono interno e 36 com conexão do tipo cone-morse, divididos em grupos, da seguinte forma: Grupo Pasta Antimicrobiana- 12 conjuntos implantes HI/conectores protéticos e 12 conjuntos implantes CM/conectores protéticos, Grupo Íons de Prata- 12 conjuntos implantes HI/conectores protéticos e 12 conjuntos implantes CM/conectores protéticos e Grupo Controle- 12 conjuntos implantes HI/conectores protéticos e 12 conjuntos implantes CM/conectores protéticos. Os implantes e os conectores protéticos foram retirados de suas embalagens para aplicação do torque final (20N/cm). Antes disso, em um dos grupos experimentais, uma camada da pasta antimicrobiana foi aplicada sobre a superfície interna dos implantes e conectores protéticos e seus respectivos parafusos. Os conjuntos implantes-conectores foram parcialmente imersos na solução de saliva humana em tubos de ensaio e incubados em estufa bacteriológica a 37°C durante 7 dias. Após esse período, amostras do conteúdo interno dos conjuntos implantes-conectores protéticos dos 3 grupos foram colhidas com o objetivo de detectar e quantificar os micro-organismos presentes, utilizando para isto, a técnica de hibridização com sondas de DNA genômico DNA Checkerboard. Os implantes de conexão do tipo cone morse apresentaram menores valores de contagem de bactérias quando comparados aos implantes hexágono interno no grupo Controle (p<0,001), já para o grupo Íons de prata e Pasta antimicrobiana, foi observado comportamento inverso, maiores valores de contagem de bactérias para os implantes Cone Morse. Comparando-se os implantes de mesma conexão, entre os 03 grupos examinados, as amostras dos implantes Cone Morse dos grupos Controle, Íons de prata e Pasta antimicrobiana apresentaram valor de contagens de micro-organismos em ordem crescente. Os implantes de conexão hexágonal interna dos grupos Controle apresentaram maiores valores de contagens de micro-organismos seguidos pelos implantes do grupo Pasta antimicrobiana e Íons de prata, respectivamente. A partir dos resultados obtidos pode-se concluir que houve a passagem dos 43 micro-organismos analisados in vitro através da interface implante/componente protético em ambos os sistemas avaliados. Para ambos os tratamentos (adição de sais de prata às paredes dos pilares protéticos e aplicação da pasta antimicrobiana no interior dos implantes) houve diminução da infiltração microbiana no interior daqueles sistemas de conexão do tipo Hexágono Interno. / The contemporary and modern dentistry has been preconized the use of dental implants for replacement of missing teeth. The micro-organisms presents in oral environment, particularly those related to periodontal disease, are responsible for the highest failure rates of dental implants. This study evaluated the occurrence of bacterial leakage through the abutmentimplant interface in Morse Taped (CM) and Hexagon Internal (HI) dental implants after the association with antimicrobial paste or addition of silver salts on the abutments. 72 titanium dental implants (Pross ® - Implant System, Dabi-Atlante, Ribeirão Preto, Brazil), 36 with internal hexagon connection type and 36 with cone-morse connection type, divided into groups as follows: group Antimicrobial Paste -12 implants HI / prosthetic connectors and 12 implants CM / prosthetic connectors, group Ion Silver-12 implants HI / prosthetic connectors and 12 implants CM / prosthetic connectors and Control Group-12 implants HI / prosthetic connectors and 12 implants CM / prosthetic connectors. The implants and prosthetic connectors have been removed from their packaging for applying of final torque (20N/cm). Previously, in one experimental group, a layer of antimicrobial paste was applied on the inner surface of implants and prosthetic connectors. The sets connector/implants were partially immersed in human saliva solution in test tubes and incubated in bacteriological oven at 37°C for 7 days. Subsequently, samples of the contents of internal prosthetic sets implantconnectors of the 3 groups were collected to detect and quantify micro-organisms, through the DNA Checkerboard Hybridization Technique. The morse taper implants had significantly lower bacterial count compared to internal hexagon implants in the control group (p <0.001), while for the group of Silver Ion and antimicrobial Paste, we observed an inverse behavior, higher counts of micro-organisms for Morse taper implants. Comparing the same connection implants, among the 03 groups examined, samples of implants Morse Taper Control groups, Antimicrobial Paste and Silver ions exhibited values of counts of micro-organisms in ascending order. The internal hexagon implants of the Control group showed higher counts of microorganisms followed by Antimicrobial Paste and Silver Ions groups, respectively. The 43 species analyzed in vitro infiltrated through the interface implant / abutment in both systems evaluated; For both the treatments (adding silver salts in the abutments walls and applying of the antimicrobial paste within the implants) there was decreased microbial leakage through the interface connection for the internal hexagon dental implants

Em invertebrados, os genes Scratch (Scrt) codificam fatores de transcrição que promovem a neurogênese durante o desenvolvimento. A função de Scrt em vertebrados é desconhecida, mas em camundongos Scrt1 e Scrt2 são especificamente expressos em neurônios pós-mitóticos no embrião e no sistema nervoso central adulto. Neste trabalho, nós clonamos a sequência codificante de Scrt2 de galinha (cScrt2) e caracterizamos seu padrão de expressão no embrião por PCR quantitativo e hibridação in situ. A sequência codificante completa foi clonada no vetor de expressão pMES-GFP e o produto previsto da tradução é uma proteína com 276 aminoácidos. A sequência de aminoácidos compartilha identidades de 70% com Scrt2 de rato e 58% com Scrt de zebrafish. Transcritos cScrt2 são detectados primeiramente na periferia do tubo neural do rombencéfalo em HH 15 e da medula espinhal em HH 17, coincidindo com os locais onde alguns dos primeiros neurônios se diferenciam durante a embriogênese. Entre HH 19-23, a expressão no domínio motor da medula espinhal se concentra progressivamente na interface entre as zonas ventricular e do manto. Além disso, a expressão de cScrt2 também é observada nos gânglios da raíz dorsal a partir de HH 22-23, principalmente no domínio dorsomedial. O campo de expressão de cScrt2 no tubo neural é complementar aos de Notch1, que é expresso em células-tronco neurais, e SCG10, marcador de neurônios diferenciados. Nossos resultados sugerem que durante a embriogênese da medula espinhal cScrt2 é especificamente expresso em neurônios pós-mitóticos indiferenciados. A construção pMES-GFP(cScrt2) possibilita futuras análises funcionais diretas por interferência gênica no embrião de galinha, que serão de grande valor para um melhor entendimento da função dos genes Scrt em vertebrados. / In invertebrates, the Scratch (Scrt) genes encode transcription factors that promote neurogenesis during development. The Scrt function in vertebrates is unknown, but in mice Scrt1 and Scrt2 are specifically expressed in post-mitotic neurons in the embryo and in the adult central nervous system. In this work, we have cloned the coding sequence of chicken Scrt2 (cScrt2) and characterized its expression pattern in the embryo with quantitative PCR and in situ hybridization. The complete coding sequence was cloned in the expression vector pMES-GFP and the predicted translation product is a 276-aminoacids protein. The aminoacid sequence shares identities of 70% with rat Scrt2 and 58% with zebrafish Scrt. cScrt2 transcripts are firstly detected in the periphery of the neural tube in the hindbrain by HH 15 and in the spinal cord by HH 17, coinciding with the places where some of the first neurons differentiate during embryogenesis. Between HH 19-23, the expression in the motor domain of the spinal cord is progressively concentrated in the interface between the ventricular and mantle zones. Furthermore, cScrt2 expression is also observed in the dorsal root ganglia after HH22-23, particularly in the dorsomedial domain. The expression pattern of cScrt2 in the neural tube is complementary to that of Notch1, which is expressed in neural stem cells, and SCG10, a marker for differentiated neurons. Our results suggest that during embryogenesis cScrt2 is specifically expressed in post-mitotic undifferentiated neurons. The construction pMES-GFP(cScrt2) makes possible future direct functional analysis by genetic interference in the chick embryo, which will be of great value for better understanding the Scrt genes function in vertebrates.

Este estudo teve como objetivos (a) identificar mecanismos pelos quais rearranjos cromossômicos citogeneticamente equilibrados possam estar associados de maneira causal a determinados quadros clínicos e (b) contribuir para a compreensão dos mecanismos de formação desses rearranjos. Para isso, foram estudados 45 rearranjos cromossômicos citogeneticamente equilibrados (29 translocações, 10 inversões e seis rearranjos complexos), detectados em pacientes que apresentavam malformações congênitas, comprometimento do desenvolvimento neuropsicomotor ou déficit intelectual. Foram 31 rearranjos cromossômicos esporádicos, três familiais que segregavam com o quadro clínico e mais 11 rearranjos cromossômicos herdados de genitores fenotipicamente normais. Inicialmente os pontos de quebra desses rearranjos foram mapeados por hibridação in situ fluorescente (FISH). A busca por microdeleções e duplicações genômicas foi realizada por a-CGH. A investigação dos pontos de quebra prosseguiu com a aplicação da técnica de Mate-Pair Sequencing (MPS), que permite localizar as quebras em segmentos de 100 pb - 1 kb, na maioria dos casos. Para obter os segmentos de junção das quebras no nível de pares de bases, os segmentos delimitados por MPS foram sequenciados pelo método de Sanger. A análise por aCGH revelou microdeleções ou microduplicações localizadas nos cromossomos rearranjados, em 12 dos 45 pacientes investigados (27%). A análise de 27 rearranjos por MPS permitiu a caracterização dos pontos de junção das quebras. MPS expandiu o número de pontos de quebra, detectados por análise do cariótipo ou aCGH, de 114 para 156 (em resolução < 2kb, na maioria dos casos). O número de pontos de quebra/rearranjo variou de 2 a 20. Os 156 pontos de quebra resultaram em 86 variantes estruturais equilibradas e outras 32 variantes não equilibradas. Perdas e ganhos de segmentos submiscroscópicos nos cromossomos rearranjados constituíram a principal causa ou, provavelmente, contribuíram para o quadro clínico de 12 dos 45 pacientes. Em cinco desses 12 rearranjos foram detectadas por MPS a interrupção de genes já relacionados à doença, ou provável alteração de sua região reguladora, contribundo para o quadro clínico. Em quatro dos 33 rearranjos não associados a perdas ou ganhos de segmentos, a análise por MPS revelou a interrupção de genes que já foram anteriormente relacionados a doenças, explicando-se, assim, as características clínicas dos portadores; outro rearranjo pode ter levando alteração da expressão gênica de gene sensível a dosagem e ao quadro clínico. Um rearranjo cromossômico familial, identificado na análise após bandamento G como uma translocação equilibrada, t(2;22)(p14;q12), segregava com quadro de atraso do desenvolvimento neuropsicomotor e dificuldade de aprendizado associados a dismorfismos. A combinação das análises por FISH, aCGH e MPS revelou que se tratava, na verdade, de rearranjo complexo entre os cromossomos 2, 5 e 22, incluindo 10 quebras. A segregação de diferentes desequilíbrios submicroscópicos em indivíduos afetados e clinicamente normais permitiu a compreensão da variabilidade clínica observada na família. Rearranjos equilibrados detectados em indivíduos afetados, mas herdados de genitores clinicamente normais, são, em geral, considerados como não tendo relação com o quadro clínico, apesar da possibilidade de desequilíbrios cromossômicos gerados por permuta desigual na meiose do genitor portador do rearranjo. Neste trabalho, a investigação de 11 desses rearranjos por aCGH não revelou perdas ou ganhos de segmentos nos cromossomos rearranjados. No entanto, a análise por aCGH da portadora de um desses rearranjos - inv(12)mat - revelou deleção de 8,7 Mb no cromossomo 8, como causa de seu fenótipo clínico. Essa deleção estava relacionada com outro rearranjo equilibrado também presente em sua mãe, independente da inversão. Para compreender os mecanismos de formação de rearranjos citogeneticamente equilibrados, investigamos os segmentos de junção no nível de pares de base. A análise por MPS que levou, na maioria dos casos, ao mapeamento dos pontos de quebras em segmentos <1kb permitiu o sequenciamento pelo método de Sanger de 51 segmentos de junções de 17 rearranjos. A ocorrência de blunt fusions ou inserções e deleções <10 pb, e a ausência de homologia ou a presença de micro homologia de 2 pb a 4 pb de extensão indicaram o mecanismo de junção de extremidades não homólogas (non-homologous end joinging; NHEJ), na maioria das 51 junções caracterizadas. As características de três dos quatro rearranjos mais complexos, com 17-20 quebras, indicaram sua formação pelo mecanismo de chromothripsis. Este estudo mostra a importância da análise genômica de variações de número de cópias por microarray, juntamente com o mapeamento dos pontos de quebra por MPS, para determinar a estrutura de rearranjos cromossômicos citogeneticamente equilibrados e seu impacto clínico. O mapeamento dos segmentos de junção por MPS, permitindo o sequenciamento pelo método de Sanger, foi essencial para a compreensão de mecanismos de formação desses rearranjos / This study aimed at (a) identifying causative mechanisms of clinical features in carriers of karyotypically balanced chromosomal rearrangements (BCRs), and (b) disclosing the mechanisms of formation of these chromosomal rearrangements. Forty-five BCRs - 29 translocations, 10 inversions and six complex rearrangements, detected in patients with intellectual disability, developmental delay and/or congenital malformations were investigated. Thirty-one rearrangements were de novo, three were familial and segregated with the clinical phenotype, and 11 BCRs were inherited from phenotypically normal parents. Initially, the breakpoints of the rearrangements were mapped by using fluorescence in situ hybridization (FISH), and the presence of cryptic genomic imbalances was investigated by array comparative genomic hybridization (a-CGH). Breakpoint-containing segments were narrowed down to approximately 100 pb - 1 kb, by using NGS-based mate-pair-sequencing (MPS). In order to investigate breakpoint junctions at the nucleotide level, breakpoint segments delimited by MPS were Sanger sequenced. De novo microimbalances on the rearranged chromosomes were detected by aCGH in 12 out of the 45 patients investigated (27%). MPS of 27 BCRs expanded the number of breakpoints, previously detected by karyotyping and aCGH, from 114 to 156 (breakpoint resolution < 2 kb, in most cases). The number of breakpoints/BCR ranged from 2 to 20. The 156 breakpoints resulted in 86 balanced and 32 unbalanced sample-specific structural variations (SVs). In 12 out of the 45 patients investigated by aCGH, microimbalaces on the rearranged chromosomes were responsible or likely contributed to the clinical features observed in the carriers. In five of these 12 rearrangements, truncated known disease genes or their regulatory regions also contributed to the clinical phenotype. MPS analysis revealed four out of the 33 rearrangements not associated with microimbalaces, truncated known disease genes, thus explaining clinical features of carriers. Another balanced rearrangement might have truncated the regulatory region of a dosage sensitive gene, thus disturbing gene expression and leading to the clinical features of the carrier. A karyotypically balanced translocation t(2;22)(p13;q12.2) associated with variable learning disabilities and dysmorphisms, was detected in six individuals in a three-generation family. Combined a-CGH, FISH and MPS revealed a ten-break complex rearrangement, also involving chromosome 5. As the consequence of the segregation of the derivative chromosomes der(2), der(5) and der(22), different microimbalances were present in affected and clinically normal family members, thus contributing to the clinical variability. Although, historically, BCRs inherited from phenotypically normal parents have not been considered as causally associated with clinical features of carriers, cryptic microimbalances on the rearranged chromosome have been reported that explained the clinical features of the affected carriers. In 11 such inherited BCRs ascertained through affected individuals, which were investigated in this work by using aCGH, no microimbalances were detected on the chromosomes involved. However, aCGH analysis in an affected girl, who carried an inv(12)mat, detected a likely pathogenic 8.7 Mb deletion on chromosome 8. This deleted chromosome derived from another maternal balanced rearrangement, not related to the inversion. In order to investigate mechanisms of BCR formation, breakpoint junctions, mapped at intervals of approximately 1 kb by MPS, were narrowed down to the nucleotide level by Sanger sequencing. Fifty-one breakpoint junctions (BPJs) from 17 BCRs (nine translocations, three inversions and five complex rearrangements) were sequenced. The occurrence of blunt fusions or <10 bp deletions, insertions or duplications in the majority of the 51 BPJs, and the absence of homology or the presence of just 2 bp to 4 bp microhomology indicated non-homologous end joining (NHEJ). In three of the four most complex BCRs (17 to 20 breaks) indicated chromothripsis as the mechanism underlying their formation. This study illustrates the importance of combining copy number variation analysis by microarray and breakpoint mapping by MPS, to determine the structure of karyotypically balanced chromosomal rearrangements, and to unravel their clinical impact. Mapping the breakpoint-junctions by MPS, followed by Sanger sequencing, was fundamental to determine the mechanism of formation of these rearrangements

Centrée sur la République Populaire de Chine actuelle, notre recherche vise à mettre en évidence les processus d’hybridation culturelle dans l’expression de la « modernité chinoise » en tant que thème publicitaire. L’hybridation irrigue les conditions de la création publicitaire en prise avec l’histoire, innerve les pratiques des créatifs et des professionnels de la publicité, imprègne les productions et créations réalisées. L’analyse d’un corpus de soixante-quinze publicités diffusées de 1979 à 2008 met en évidence l’apport continu d’influences extérieures sur les arts visuels de masse et le contexte de création, les tensions et négociations suscitées par la constitution d’un imaginaire de la « modernité chinoise ». L’imprégnation de l’hybridation au cœur des indices et des énoncés laisse intacts les cadres englobants du discours. / Focused on the current period of Popular Republic of China, our research aims at highlighting the cultural hybridization process at play in the expression of “Chinese modernity”. Hybridization is part of the advertising creation conditions, the professionals’ practices and the creations themselves. The analysis of seventy-five print advertisements released between 1979 and 2008 shows the continuous impact of foreign influences on the creation context in Chinese contemporary visual arts, the tensions and negotiations generated by the constitution of a “Chinese modernity” imaginary. The hybridization of indexes and utterances leaves global discourse frameworks intact.

L’évolution des nouvelles pratiques de l’investissement socialement responsable ouvre la voie à des modes d’organisation innovants. Un grand marché est né entre l’offre et la demande, de nouvelles « architectures transactionnelles » proposant des émissions obligataires socialement responsables voient le jour. L’objectif étant de créer la liquidité et de contribuer au développement économique et social. L'étude des arrangements organisationnels qui ont abouti à émettre une obligation socialement responsable à destination de la société de gestion se nourrit de deux expériences pionnières. Le contexte organisationnel nous amène à nous interroger sur la place du gérant de fonds dans le financement de l’économie solidaire. La société de gestion de portefeuille, acteur majeur au coeur des modes d’organisations, se positionne entre les émetteurs d’obligations et les investisseurs souhaitant intégrer des critères extra-financiers dans leurs choix de sélection de portefeuille. La problématique de notre travail de recherche s'intéresse à l'étude de l’attractivité des gestionnaires d’actifs face à des mécanismes différenciés d' Economie Sociale et Solidaire. Ainsi, dans le cadre de cette thèse, nous proposons d'étudier la perception du point de vue du gérant de fonds de deux modes d'organisation différents, qui aboutissent à la construction d'un produit qualifié d’ISR dans le sens où il répond aux attentes des investisseurs souhaitant intégrer des dimensions extra-financières dans leurs choix de sélection de produits. Dans cette optique, le gérant de fonds ISR est amené à prendre des décisions quant au choix des produits dans son processus de construction du portefeuille. Il joue un double rôle de constructeur de performance ESG et d'intermédiaire financier et doit faire face à un ensemble de contraintes de gestion mais aussi vis-à-vis de ses partenaires. / The evolution of the new practices of the socially responsible investment opens the way for innovative modes of organization. A big market was born between supply and demand, new "transactional architectures" proposing socially responsible bond issues. The objective being to create the liquidity and to contribute to the economic and social development.The study of the organizational arrangements which succeeded to emit a socially responsible obligation aimed at the management company feeds on two experiences pioneers. The organizational context brings us to wonder about the place of the fund manager in the financing of the united economy. The asset management, at the heart of the organization modes, is positioned between the bond issuer and the investors wishing to integrate extra-financial dimension into their choices of selection of asset.The problem of our research work is interested in the study of the attractiveness of the asset managers in the face of mechanisms differentiated of Voluntary and united Sector.So, within the framework of this thesis, we suggest studying the perception from the point of view of the fund manager of two different modes of organization, which end in the construction of a product qualified as SRI in the sense where he meets the expectations of investors wishing to integrate extra-financial dimensions into their choices of selection of products.From this perspective, the fund manager SRI is brought to make decisions as for the choice of products in its process of construction of the portfolio. He plays double role of construction social performance and financial intermediary and has to face a set of constraints of management but also towards these partners.

Cette thèse interroge la typographie contemporaine au prisme du postmodernisme des années 1980 jusqu'au début des années 2000 afin de montrer que celle-ci va au-delà du simple outil de communication visuelle et de technique d'impression. Dans ce but, cette recherche revient sur l'histoire de la typographie pour en soulever les problématiques récurrentes (idéal de beauté, lisibilité, pluridisciplinarité) retravaillées et ré-étudiées par le postmodernisme. Outre les effets stylistique, le postmodernisme se pose en opposition et réaction au modernisme qu'il remet en cause en tant que modèle dominant. Les problématiques qui découlent de cette remise en question, interrogent la légitimité du designer ainsi que sa place dans la société, dans le processus de création. La typographie et son statut sont parties prenantes de ce débat qui permet de l'extraire du simple objet imprimé. Cette thèse interroge donc la possibilité de considérer la typographie comme objet esthétique et critique qui pense et se pense, à partir des discussions et travaux de cette période, ainsi qu'en s'appuyant tout particulièrement sur la recherche en design. Cette démarche permet également de mettre en perspective la recherche et les savoirs actuels autour de la typographie afin de faire émerger les paradoxes de cette dernière et d'aboutir à sa redéfinition. / This thesis is about contemporary typography in the light of postmodernism from the eighties to the early years of the new millenium in order to show that it goes beyond the mere tool of visual communication and printing technique. So the research relates the history of typography and raises the recurrent issues (ideal of beauty, lisiblility, multi-disciplinarity) worked out and studied by postmodernism. Beside the stylistic effects, postmodernism stands out by reaction to modernism which it questions as a prevailing pattern. The deriving problems raise the question of whether the designer is legitimate and what his/her position in society is, in the creative process. Typography and its status are part and parcel of this issue which helps take it from the mere printed object. Thus, this thesis raises the question of whether it is possible to consider typography as an aesthetic and critical object which thinks, from the talks and works of that period, by particularly drawing upon research in design. This process also helps put into perspective the analysis and current knowledge around typography in order to develop its paradoxes and lead to re-define its goal.

Submitted by (ana.araujo@ufrpe.br) on 2017-02-07T16:48:16Z No. of bitstreams: 1 Daniel Oliveira Jordao do Amaral.pdf: 1158857 bytes, checksum: e7a95fb82b8780bf1c190ef328318925 (MD5) / Made available in DSpace on 2017-02-07T16:48:16Z (GMT). No. of bitstreams: 1 Daniel Oliveira Jordao do Amaral.pdf: 1158857 bytes, checksum: e7a95fb82b8780bf1c190ef328318925 (MD5) Previous issue date: 2007-06-14 / To identify tomato plant (Lycopersicon esculentum Mill), cv. BRH, genes which answer to plant pathogen Fusarium oxysporum f. sp. lycopersici and salicylic acid, the carrier molecule for activation of responses of plant defense, it was used the suppression subtractive hybridization (SSH) technique, from leaf cDNAs, 24h after salicylic acid, library denominated AS, and root cDNA, 72h after inoculation with F. oxysporum f. sp. lycopersici, incompatible interaction, library denominated FO. This work represents the first report of global gene expression of tomato plant induced by salicylic acid and F. oxysporum f. sp. lycopersici, using SSH technique; it was identified a total of 307 clones in the two subtractive libraries, being 143 obtained in the AS library and 164 in the FO library. Probable functions for genes were obtained by sequencing of clones and subsequent homology research at datas. These isolated genes are involved in several processes related to resistance against plant pathogen such as: hypersensitive response, programmed cell death, synthesis and transport of antimicrobial metabolites, signal perception and transduction, synthesis of pathogenesis-related proteins, lipid metabolism and selective degradation of proteins. It was identified in FO library a higher number of defense-related genes (26%) than in AS library (24%). In relation to the number of genes encoding antimicrobial proteins, they were only found in FO library (7%). However, genes involved in secondary compound metabolism were higher in AS library (13%) in relation to FO library (4%). These genes related to controlled degradation of proteins were also higher in AS library (3%) than in FO library (1%). The results suggest that the resistance of tomato plant induced by salicylic acid and by plant pathogen occur by distinct mechanisms. / Com o propósito de identificar genes no tomateiro (Lycopersicon esculentum Mill), cv. BRH, que respondem ao fitopatógeno Fusarium oxysporum f. sp. lycopersici e ao ácido salicílico, molécula mensageira na ativação de resposta de defesa em plantas, foi utilizada a técnica de hibridização subtrativa por supressão (HSS), a partir de cDNAs de folhas, 24h após o tratamento com ácido salicílico, biblioteca denominada (AS), e cDNAs de raízes, 72h após a inoculação com Fusarium oxysporum f. sp. lycopersici, interação incompatível, biblioteca denominada (FO). Esse trabalho representa o primeiro relato da expressão gênica global no tomateiro induzido pelo ácido salicílico e pelo F. oxysporum f. sp. lycopersici, utilizando a técnica HSS. Foram identificados um total de 307 clones nas duas bibliotecas subtraídas, sendo 143 clones obtidos na biblioteca (AS) e 164 clones na biblioteca FO. As prováveis funções dos genes foram obtidas pelo sequenciamento dos clones e subseqüente pesquisa de homologia em bancos de dados. Os genes encontrados estão envolvidos em diversos processos relacionados à resistência contra fitopatógenos como: resposta de hipersensibilidade, morte celular programada, síntese e transporte de metabólicos antimicrobianos, percepção e transdução de sinal, síntese de proteínas relacionadas à patogênese, metabolismo de lipídeos e degradação controlada de proteínas. Foram identificados na biblioteca FO um número maior de genes implicados em mecanismos de defesa (26%), do que na biblioteca AS (24%). Em relação ao número de genes codificadores de proteínas antimicrobianas foram encontrados apenas na biblioteca FO (7%). Entretanto, os genes envolvidos no metabolismo de compostos secundários foi maior na biblioteca AS (13%) em relação a biblioteca FO (4%). Os genes relacionados a degradação controlada de proteínas também foi maior na biblioteca AS (3%) do que na biblioteca FO (1%). Os resultados obtidos sugerem que a resistência no tomateiro induzido pelo ácido salicílico e pelo patógeno ocorre por mecanismos distintos.