Genetic analysis of chromosomal regions 2q33, 7q32 and 19q13 in multiple sclerosis susceptibility

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS) affecting 0.1-0.2% of Northern European descent population. MS is considered to be a multifactorial disease, both environment and genetics play a role in its pathogenesis. Despite several decades of intense research, the etiological and pathogenic mechanisms underlying MS remain still largely unknown and no curative treatment exists. The genetic architecture underlying MS is complex with multiple genes involved. The strongest and the best characterized predisposing genetic factors for MS are located, as in other immune-mediated diseases, in the major histocompatibility complex (MHC) on chromosome 6. In humans MHC is called human leukocyte antigen (HLA). Alleles of the HLA locus have been found to associate strongly with MS and remained for many years the only consistently replicable genetic associations. However, recently other genes located outside the MHC region have been proposed as strong candidates for susceptibility to MS in several studies. In this thesis a new genetic locus located on chromosome 7q32, interferon regulatory factor 5 (IRF5), was identified in the susceptibility to MS. In particular, we found that common variation of the gene was associated with the disease in three different populations, Spanish, Swedish and Finnish. We also suggested a possible functional role for one of the risk alleles with impact on the expression of the IRF5 locus. Previous studies have pointed out a possible role played by chromosome 2q33 in the susceptibility to MS and other autoimmune disorders. The work described here also investigated the involvement of this chromosomal region in MS predisposition. After the detection of genetic association with 2q33 (article-1), we extended our analysis through fine-scale single nucleotide polymorphism (SNP) mapping to define further the contribution of this genomic area to disease pathogenesis (article-4). We found a trend (p=0.04) for association to MS with an intronic SNP located in the inducible T-cell co-stimulator (ICOS) gene, an important player in the co-stimulatory pathway of the immune system. Expression analysis of ICOS revealed a novel, previously uncharacterized, alternatively spliced isoform, lacking the extracellular domain that is needed for ligand binding. The stability of the newly-identified transcript variant and its subcellular localization were analyzed. These studies indicated that the novel isoform is stable and shows different subcellular localization as compared to full-length ICOS. The novel isoform might have a regulatory function, but further studies are required to elucidate its function. Chromosome 19q13 has been previously suggested as one of the genomic areas involved in MS predisposition. In several populations, suggestive linkage signals between MS predisposition and 19q13 have been obtained. Here, we analysed the role of allelic variation in 19q13 by family based association analysis in 782 MS families collected from Finland. In this dataset, we were not able to detect any statistically significant associations, although several previously suggested markers were included to the analysis. Replication of the previous findings on the basis of linkage disequilibrium between marker allele and disease/risk allele appears notoriously difficult because of limitations such as allelic heterogeneity. Re-sequencing based approaches may be required for elucidating the role of chromosome 19q13 with MS. This thesis has resulted in the identification of a new MS susceptibility locus (IRF5) previously associated with other inflammatory or autoimmune disorders, such as SLE. IRF5 is one of the mediators of interferons biological function. In addition to providing new insight in the possible pathogenetic pathway of the disease, this finding suggests that there might be common mechanisms between different immune-mediated disorders. Furthermore the work presented here has uncovered a novel isoform of ICOS, which may play a role in regulatory mechanisms of ICOS, an important mediator of lymphocyte activation. Further work is required to uncover its functions and possible involvement of the ICOS locus in MS susceptibility.

Varities of National Metonymy in Media Accounts of International Mergers and Acquisitions

International mergers and acquisitions (M&As) often invoke national identification and national cultural differences. We argue that metonymy is a central linguistic resource through which national cultural identities and differences are reproduced in media accounts of international M&As. In this paper, we focus on two revealing cases: the acquisition of American IBM Personal Computer Division (PCD) by the Chinese company Lenovo and the acquisition of American Anheuser-Busch (A-B) by the Belgian-Brazilian company InBev. First, we identify the forms, functions and frequencies of national metonymy in media accounts of these cases. We present a typology that classifies varieties of national metonymy in international M&As. Second, we demonstrate how these metonyms combine with metaphor to generate evocative imagery, engaging wit, and subversive irony. Our findings show that national metonymy contributes to the construction of emotive frames, stereotypes, ideological differences, and threats. Combinations of national metonymy with metaphor also provide powerful means to construct cultural differences. However, combinations of metonymy with wit and irony enable the play on meanings that overturns and resists national and cultural stereotypes. This is the first study to unpack the deployment of metonymy in accounts of international M&As. In doing so, it also opens up new avenues for research into international management and the analysis of tropes in management and organization.

Validation of a Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR)

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Processing Facilitation Strategies in OV and VO Languages: A Corpus Study

The present corpus study aimed to examine whether Basque (OV) resorts more often than Spanish (VO) to certain grammatical operations, in order to minimi ze the number of arguments to be processed before the verb. Ueno & Polinsky (2009) argue that VO/OV languages use certain grammatical resources with different frequencies in order to facilitate real-time processing. They observe that both OV and VO languages in their sample (Japanese, Turkish and Spanish) have a similar frequency of use of subject pro-drop; however, they find that OV languages (Japanese, Turkish) use more intransitive sentences than VO languages (English, Spanish), and conclude this is an OV-specific strategy to facilitate processing. We conducted a comparative corpus study of Spanish (VO) and Basque (OV). Results show (a) that the fre- quency of use of subject pro-drop is higher in Basque than in Spanish; and (b) Basque does not use more intransitive sentences than Spanish; both languages have a similar frequency of intransitive sentences. Based on these findings, we conclude that the frequency of use of grammatical resources to facilitate the processing does not depend on a single typological trait (VO/OV) but it is modulated by the concurrence of other grammatical feature.

O humor verbal e o livro didático de língua portuguesa: uma análise do aproveitamento didático do humor

Esta tese de doutorado desenvolve considerações a respeito do humor verbal e o seu aproveitamento pedagógico em livros didáticos de Língua Portuguesa. Nosso interesse foi examinar o humor verbal e os mecanismos linguísticos que o provocam, para verificar de que forma foram abordados pelos livros didáticos. Antes de proceder à análise, fizemos breve exposição das principais teorias que estudaram o humor verbal (aquele provocado pelos recursos que a língua oferece). Tratamos também da relevância da escolha das palavras para o texto de humor. Abordamos como os aspectos semânticos (polissemia, homonímia, paronímia, sinonímia, antonímia), semióticos (o papel da iconicidade lexical e da linguístico-gramatical) e pragmáticos (pressupostos, inferências, entre outros) podem contribuir para a construção do(s) sentido(s) do texto humorístico. Como os fenômenos linguísticos não ocorrem isoladamente, uma vez que só se materializam em textos, examinamos em especial os gêneros de humor; os aspectos da textualidade (em especial, a coesão e a coerência) e a relação entre a leitura e o humor (como o desenvolvimento de habilidades e competências de leitura do texto de humor podem ser aplicadas a textos de natureza não humorística). Realizamos breve retrospecto da história do livro didático no Brasil para compreender de que maneira o texto de humor foi sendo incorporado a esse material didático. Analisamos nosso córpus, procurando observar como os textos humorísticos foram abordados: em sua condição de gêneros textuais ou apenas com o propósito de exemplificar ou servir de pretexto para o ensino de algum conteúdo de cunho gramatical; se o humor verbal foi aproveitado e de que forma ocorreu essa abordagem (se a expressividade dos recursos linguísticos foi salientada). O humor verbal oferece rico material sobre a língua portuguesa e pode enriquecer as aulas de língua materna, o que vem a confirmar a relevância da presente pesquisa

Key issues in the study of new and alternative social movements in Spain: The Left, Identity and Globalizing Processes

This article highlights the importance of dedicating a whole special issue on New and Alternative Social movements in Spain. It sets the basis for this endeavour by emphasizing the importance of the 2004, unexpected, electoral victory of the Spanish socialists, and the subsequent satisfaction of the important demands promoted by certain social movements actors and Spanish society in general (the withdrawal of Spanish troops from Iraq, the cancellation of the National Hydrological Plan and the Legalization of same sex marriages. The view supported is that these developments signify the end of a protest cycle, which could have the same effect with the early 1980s socialist victory. After a discussion around the low associationalism that characterizes Spanish society and recent experience of authoritarianism, it is suggested that it is time for the study of new and alternative social movements in Spain and other south European societies to move beyond the emphasis on exceptionality but appreciate differences by focusing on the available political opportunities and the identity of social movement actors. The remainder of the article is dedicated to introducing the contributing articles.

Crossing borders: Space and identity in the essay by Angelina Muñiz

In this study, we establish a relation between the representation of space in Muñiz’s essays and the construction of the essayist’s complex identity which combines Spanish, Jewish and Mexican traits. We concentrate on Angelina Muñiz’s essays Las raíces y las ramas (1993) and El canto del peregrino (1999). Methodologically, we rely on Maingueneau’s concept of ‘scenography’, according to which the text stages its own situation of enunciation. Our starting point is the triple Spanish-Jewish-Mexican identity of the essayist. Our research question is about how the essayist deals with the space corresponding to respectively the Spanish and Mexican part of her identity. Secondly, we analyse the representation in the essays of a space corresponding to her Jewish roots. We find that Muñiz’s vision of space is not static; the essayist’s vision on space is dynamic, open, free and characterized by a constant free movement across national borders. Similar to the concept of space of the ‘diaspora’, her vision is constructed without the limitations imposed by national borderlines or geographical distances.

The Analogical Peacock Hypothesis: The Sexual Selection of Mind-Reading and Relational Cognition in Human Communication

This integrative review presents a novel hypothesis as a basis for integrating two evolutionary viewpoints on the origins of human cognition and communication, the sexual selection of human mental capacities, and the social brain hypothesis. This new account suggests that mind-reading social skills increased reproductive success and consequently became targets for sexual selection. The hypothesis proposes that human communication has three purposes: displaying mind-reading abilities, aligning and maintaining representational parity between individuals to enable displays, and the exchange of propositional information. Intelligence, creativity, language, and humor are mental fitness indicators that signal an individual’s quality to potential mates, rivals, and allies. Five features central to the proposed display mechanism unify these indicators, the relational combination of concepts, large conceptual knowledge networks, processing speed, contextualization, and receiver knowledge. Sufficient between-mind alignment of conceptual networks allows displays based upon within-mind conceptual mappings. Creative displays communicate previously unnoticed relational connections and novel conceptual combinations demonstrating an ability to read a receiver’s mind. Displays are costly signals of mate quality with costs incurred in the developmental production of the neural apparatus required to engage in complex displays and opportunity costs incurred through time spent acquiring cultural knowledge. Displays that are fast, novel, spontaneous, contextual, topical, and relevant are hard-to-fake for lower quality individuals. Successful displays result in elevated social status and increased mating options. The review addresses literatures on costly signaling, sexual selection, mental fitness indicators, and the social brain hypothesis; drawing implications for nonverbal and verbal communication.

Laughter and Humour as Conversational Mind-Reading Displays

Laughter and humor are pervasive phenomena in conversa- tional interactions. This paper argues that they function as displays of mind-reading abilities in social interactions–as suggested by the Analogi- cal Peacock Hypothesis (APH). In this view, they are both social bonding signals and can elevate one’s social status. The relational combination of concepts in humor is addressed. However, it is in the inclusion of context and receiver knowledge, required by the APH view, that it contributes the most to existing theories. Taboo and offensive humor are addressed in terms of costly signaling, and implications for human computer inter- action and some possible routes to solutions are suggested.

Natural substances and high pressure processing to preserve sea bass

Esta tese teve como objectivo estudar estratégias de conservação de pescado fresco, recorrendo ao uso de extractos e óleos essenciais de plantas e do processamento por alta pressão (HPP), usando filetes de robalo como um caso de estudo modelo. Relativamente aos extractos e óleos essenciais, avaliaram-se as suas propriedades antibacterianas e antioxidantes. Os extractos aquosos quente de poejo e de orégão e o óleo essencial de cravinho apresentaram a maior actividade antioxidante. Os óleos essenciais foram mais eficientes do que os extractos para inibir o crescimento das estirpes bacterianas testadas, tendo-se observado os menores valores de concentração mínima inibitória nos óleos essenciais de orégão, citronela, alho e orégão Espanhol. De seguida, estudou-se o efeito dos óleos essenciais de orégão Espanhol e de limão na conservação de filetes de robalo fresco tendo em conta critérios microbiológicos, químicos, físicos e sensoriais. A aplicação do óleo essencial de orégão Espanhol aumentou o tempo de vida útil dos filetes sob o ponto de vista bacteriano, mas não em termos sensoriais. A combinação dos óleos essenciais de orégão Espanhol e de limão melhorou o efeito antioxidante e reduziu a intensidade do odor e a sua eficácia em relação às Enterobacteriaceae, comparando com o tratamento com óleo essencial de orégão Espanhol per se. No sentido de reduzir o odor conferido pelos óleos essenciais realizou-se um estudo de conservação para avaliar o efeito de películas com óleos essenciais (citronela, alho e tomilho) em filetes de robalo, recorrendo a uma teste de desafio bacteriano. As películas sem óleos essenciais aumentaram o tempo de vida útil sob o ponto de vista bacteriano, mas este efeito não foi observado com a incorporação dos óleos essenciais nas películas. Em relação ao HPP, testaram-se diversas condições (nível de pressão, tempo de pressurização e taxa de pressurização) e avaliaram-se os efeitos na actividade enzimática, na qualidade global e na conservação de filetes de robalo fresco. Em geral, o aumento do nível de pressão e do tempo de pressurização diminuiu a actividade da fosfatase ácida e das enzimas proteolíticas, a carga bacteriana e a capacidade de retenção de água, enquanto que os filetes ficaram mais brancos. O HPP revelou potencial para o desenvolvimento de novos produtos: mais brancos, não translúcidos, mais firmes e com maior tempo de frescura e estabilidade microbiológica. Em conclusão, os óleos essenciais e o HPP têm potencial para conservar pescado fresco, devido aos seus efeitos na qualidade bacteriana. Ainda assim, mais esforços devem ser feitos no sentido de reduzir a transferência de odor dos óleos essenciais para o pescado e os efeitos do HPP no aspecto do pescado e na oxidação lipídica.

(Un)settling the Irish emigrant identity: representation and construction of an Irish emigrant/exile identity in the travel narratives of Kathleen Nevin and William Bulfin

Through an examination of the travel works of William Bulfin, Tales of the Pampas (1900) and Kathleen Nevin's You'll Never Go Back this paper considers the representation of the Irish in Argentina and the contribution of these narratives in the construction of identity and the reconstruction of the emigrant identity into an exilic one. Escaping one colonial framework (Britain/Ireland), travelling to and writing from within another postcolonial construct (Argentina and the Spanish Empire), this paper analyses how Bulfin and Nevin use language as a tool to construct, and even invent, an Irish identity. This identity is inextricably linked to home and the desire to return there. Despite this desire, Argentina becomes internalised to some extent, which in Bulfin can be seen in the mix of the Spanish, English and Irish languages in his stories, highlighting that the Irish were doing with language what they had already done with their lives; trying to adapt it to their new situation. In Nevin, the contrast between us and them (Irish and 'Native') demonstrates her attempts to shape an exilic rather than emigrant mentality. Through these texts I analyse how Argentina never quite becomes a new home, but a place where Irish identity is played out and acquires form.

Collection of Canadian periodical clippings and Peninsular Game Club of St. Catharines broadside, 1874, [1910-1950]

Items include: 13 small poems clipped from newspapers. None of the poems list authors. Most of the poems are based on life lessons. Clippings of short stories which appear to have come from a St. Catharines newspaper. The stories include anecdotes, humour and medical advice. There is no author listed on any of the stories. 2 coloured sewing machine advertisements each measuring 9 cm. x 13 cm. and 9 cm. x 14 cm. 1 broadside measuring 27 cm. x 37 cm. and posted by the Peninsular Game Club of St. Catharines. The broadside is a copy of the game laws of 1874 with a warning that breach of these laws will bring rigorous prosecution.

Reliable entertainment: Spanish consumers' preferences regarding a film's country of origin

This article contributes to the study of cinema audiences in Europe by analyzing the actual behavior of Spanish moviegoers and their level of satisfaction. We modeled moviegoers’ choice of film by country of origin (U.S.A., Spain, and other countries) according to a set of determinants: (1) consumers’ interpretation of several sources of information, (2) motivations and (3) choice rules. We found three clear consumer stereotypes related to each type of film: (1) U.S.A. films were preferred by almost everyone (especially families and younger audiences); (2) Spanish films had audiences composed of middle-age and middle-class moviegoers; and (3) European productions were preferred by a social or intellectual elite. U.S.A. films dominate the Spanish market for the reason that they provide most of what moviegoers prefer, namely, familiar, reliable entertainment in Spanish; three characteristics that are not satisfied by Spanish and European films. Additionally, we discuss the implications for the European cultural policy