Bcl-xL (S49) and (S62) sequential phosphorylation/dephosphorylation during mitosis prevents chromosome instability and aneuploidy

Une caractéristique intéressante de la protéine Bcl-xL est la présence d'un domaine en boucle non-structurée entre les hélices α1 and α2 de la protéine. Ce domaine protéique n'est pas essentiel pour sa fonction anti-apoptotique et absent chez CED-9, la protéine orthologue chez Caenorhabditis elegans. A l'intérieur de ce domaine, Bcl-xL subit une phosphorylation et déphosphorylation dynamique sur les résidus Ser49 et Ser62 en phase G2 du cycle cellulaire et lors de la mitose. Lorsque ces résidus sont mutés et les protéines exprimées dans des cellules cancéreuses, les cellules démontrent plusieurs défauts mitotiques liés à l'instabilité chromosomique. Pour analyser les effets de Bcl-xL Ser49 et Ser62 dans les cellules normales, les présentes études ont été réalisées dans des cellules diploïdes humaines normales, et in vivo chez Caenorhabditis elegans. Dans une première étude, nous avons utilisé la lignée cellulaire de cellules fibroblastiques diploïdes humaines normales BJ, exprimant Bcl-xL (type sauvage), (S49A), (S49D), (S62A), (S62D) et les double (S49/62A) et (S49/62D) mutants. Les cellules exprimant les mutants de phosphorylation ont montré des cinétiques de doublement de la population cellulaire réduites. Ces effets sur la cinétique de doublement de la population cellulaire corrèle avec l'apparition de la sénescence cellulaire, sans impact sur les taux de mort cellulaire. Ces cellules sénescentes affichent des phénotypes typiques de sénescence associés notamment à haut niveau de l'activité β-galactosidase associée à la sénescence, la sécrétion d' interleukine-6, l'activation de p53 et de p21WAF1/ Cip1, un inhibiteur des complexes kinase cycline-dépendant, ainsi que la formation de foyers de chromatine nucléaire associés à γH2A.X. Les analyses de fluorescence par hybridation in situ et des caryotypes par coloration au Giemsa ont révélé que l'expression des mutants de phosphorylation de Bcl-xL provoquent de l'instabilité chromosomique et l'aneuploïdie. Ces résultats suggèrent que les cycles de phosphorylation et déphosphorylation dynamiques de Bcl-xL Ser49 et Ser62 sont importants dans le maintien de l'intégrité des chromosomes lors de la mitose dans les cellules normales. Dans une deuxième étude, nous avons entrepris des expériences chez Caenorhabditis elegans pour comprendre l'importance des résidus Ser49 et Ser62 de Bcl-xL in vivo. Les vers transgéniques portant les mutations de Bcl-xL (S49A, S62A, S49D, S62D et S49/62A) ont été générés et leurs effets ont été analysés sur les cellules germinales des jeunes vers adultes. Les vers portant les mutations de Bcl-xL ont montré une diminution de ponte et d'éclosion des oeufs, des variations de la longueur de leurs régions mitotiques et des zones de transition, des anomalies chromosomiques à leur stade de diplotène, et une augmentation de l'apoptose des cellules germinales. Certaines de ces souches transgéniques, en particulier les variants Ser/Ala, ont également montré des variations de durée de vie par rapport aux vers témoins. Ces observations in vivo ont confirmé l'importance de Ser49 et Ser62 à l'intérieur du domaine à boucle de Bcl-xL pour le maintien de la stabilité chromosomique. Ces études auront une incidence sur les futures stratégies visant à développer et à identifier des composés qui pourraient cibler non seulement le domaine anti-apoptotique de la protéine Bcl-xL, mais aussi son domaine mitotique pour la thérapie du cancer.

On Experiencers and Minimality

This dissertation is concerned with experiencer arguments, and what they tell us about the grammar. There are two main types of experiencers I discuss: experiencers of psychological verbs and experiencers of raising constructions. I question the notion of ‘experiencers’ itself; and explore some possible accounts for the ‘psych-effects’. I argue that the ‘experiencer theta role’ is conceptually unnecessary and unsustained by syntactic evidence. ‘Experiencers’ can be reduced to different types of arguments. Taking Brazilian Portuguese as my main case study, I claim that languages may grammaticalize psychological predicates and their arguments in different ways. These verb classes exist in languages independently, and the psych-verbs behavior can be explained by the argument structure of the verbal class they belong to. I further discuss experiencers in raising structures, and the defective intervention effects triggered by different types of experiencers (e.g., DPs, PPs, clitics, traces) in a variety of languages. I show that defective intervention is mostly predictable across languages, and there’s not much variation regarding its effects. Moreover, I argue that defective intervention can be captured by a notion of minimality that requires interveners to be syntactic objects and not syntactic occurrences (a chain, and not a copy/trace). The main observation is that once a chain is no longer in the c-command domain of a probe, defective intervention is obviated, i.e., it doesn’t apply. I propose a revised version of the Minimal Link Condition (1995), in which only syntactic objects may intervene in syntactic relations, and not copies. This view of minimality can explain the core cases of defective intervention crosslinguistically.

Parsing, Generation and Grammar

Humans use their grammatical knowledge in more than one way. On one hand, they use it to understand what others say. On the other hand, they use it to say what they want to convey to others (or to themselves). In either case, they need to assemble the structure of sentences in a systematic fashion, in accordance with the grammar of their language. Despite the fact that the structures that comprehenders and speakers assemble are systematic in an identical fashion (i.e., obey the same grammatical constraints), the two ‘modes’ of assembling sentence structures might or might not be performed by the same cognitive mechanisms. Currently, the field of psycholinguistics implicitly adopts the position that they are supported by different cognitive mechanisms, as evident from the fact that most psycholinguistic models seek to explain either comprehension or production phenomena. The potential existence of two independent cognitive systems underlying linguistic performance doubles the problem of linking the theory of linguistic knowledge and the theory of linguistic performance, making the integration of linguistics and psycholinguistic harder. This thesis thus aims to unify the structure building system in comprehension, i.e., parser, and the structure building system in production, i.e., generator, into one, so that the linking theory between knowledge and performance can also be unified into one. I will discuss and unify both existing and new data pertaining to how structures are assembled in understanding and speaking, and attempt to show that the unification between parsing and generation is at least a plausible research enterprise. In Chapter 1, I will discuss the previous and current views on how parsing and generation are related to each other. I will outline the challenges for the current view that the parser and the generator are the same cognitive mechanism. This single system view is discussed and evaluated in the rest of the chapters. In Chapter 2, I will present new experimental evidence suggesting that the grain size of the pre-compiled structural units (henceforth simply structural units) is rather small, contrary to some models of sentence production. In particular, I will show that the internal structure of the verb phrase in a ditransitive sentence (e.g., The chef is donating the book to the monk) is not specified at the onset of speech, but is specified before the first internal argument (the book) needs to be uttered. I will also show that this timing of structural processes with respect to the verb phrase structure is earlier than the lexical processes of verb internal arguments. These two results in concert show that the size of structure building units in sentence production is rather small, contrary to some models of sentence production, yet structural processes still precede lexical processes. I argue that this view of generation resembles the widely accepted model of parsing that utilizes both top-down and bottom-up structure building procedures. In Chapter 3, I will present new experimental evidence suggesting that the structural representation strongly constrains the subsequent lexical processes. In particular, I will show that conceptually similar lexical items interfere with each other only when they share the same syntactic category in sentence production. The mechanism that I call syntactic gating, will be proposed, and this mechanism characterizes how the structural and lexical processes interact in generation. I will present two Event Related Potential (ERP) experiments that show that the lexical retrieval in (predictive) comprehension is also constrained by syntactic categories. I will argue that the syntactic gating mechanism is operative both in parsing and generation, and that the interaction between structural and lexical processes in both parsing and generation can be characterized in the same fashion. In Chapter 4, I will present a series of experiments examining the timing at which verbs’ lexical representations are planned in sentence production. It will be shown that verbs are planned before the articulation of their internal arguments, regardless of the target language (Japanese or English) and regardless of the sentence type (active object-initial sentence in Japanese, passive sentences in English, and unaccusative sentences in English). I will discuss how this result sheds light on the notion of incrementality in generation. In Chapter 5, I will synthesize the experimental findings presented in this thesis and in previous research to address the challenges to the single system view I outlined in Chapter 1. I will then conclude by presenting a preliminary single system model that can potentially capture both the key sentence comprehension and sentence production data without assuming distinct mechanisms for each.

On the suboptimality of the p-version interior penalty discontinuous Galerkin method

We address the question of the rates of convergence of the p-version interior penalty discontinuous Galerkin method (p-IPDG) for second order elliptic problems with non-homogeneous Dirichlet boundary conditions. It is known that the p-IPDG method admits slightly suboptimal a-priori bounds with respect to the polynomial degree (in the Hilbertian Sobolev space setting). An example for which the suboptimal rate of convergence with respect to the polynomial degree is both proven theoretically and validated in practice through numerical experiments is presented. Moreover, the performance of p- IPDG on the related problem of p-approximation of corner singularities is assessed both theoretically and numerically, witnessing an almost doubling of the convergence rate of the p-IPDG method.

Perifrasi verbali con εἰμί più participio nelle varianti del Pentateuco dei LXX

Nell’articolo sono raccolte e discusse le varianti con εἰμί più participio individuate nei testimoni della tradizione testuale del Pentateuco dei LXX; sono considerate anche le varianti con γίνομαι ma solo quelle concerneti il predicato nominale. La finalità è di osservare se vi siano tracce dell’affermazione della perifrasi nelle varianti, eventuali concentrazioni di frequenza insieme a sfumature d’uso, con particolare attenzione alla datazione dei testimoni dove appaiono. Un paragrafo è riservato anche alle varianti di costruzioni con predicato nominale (copula + aggettivo) rispetto a un verbo finito.

Release of available nitrogen from river-discharged dissolved organic matter by heterotrophic bacteria associated with the cyanobacterium Microcystis aeruginosa

The use of riverine dissolved organic matter by the heterotrophic bacteria associated with a culture of the cyanobacterium Microcystis aeruginosa and release of simple nitrogen compounds were studied in an experimental series. Bacteria reduced the bulk of dissolved organic nitrogen (DON) by half, but when associated with M. aeruginosa, DON was excreted and its concentration rose by 13%. During the stationary growth phase bacteria released ammonium, doubling the concentration of ammonia as well as of nitrates. Bacteria associated with M. aeruginosa consumed riverine DON and joined the ammonification and nitrification process, supplying cyanobacteria with simple nitrogen compounds.

Português língua de herança em contexto plurilingue na Finlândia : aspetos de aquisição/aprendizagem da competência pragmática e expressão da delicadeza

Os fluxos migratórios das últimas décadas têm contribuído para que as comunidades de falantes de português se estabeleçam um pouco por todo o mundo, nomeadamente, nos países escandinavos. Um desses países de acolhimento, a Finlândia, tem desenvolvido esforços para a integração dos imigrantes que aí se estabelecem, designadamente, através da promoção de políticas de língua, que visam o ensino da língua de herança aos alunos em idade escolar. Tem sido neste contexto que as pequenas comunidades lusófonas, a viverem no país, têm podido facultar aos filhos, imigrantes de primeira e segunda gerações, acesso ao ensino formal da sua língua de herança, o português. Os sujeitos da nossa amostra fazem parte de uma dessas pequenas comunidades e residem em Tampere, na Finlândia, onde frequentam escolas cuja língua de ensino é o finlandês. O presente trabalho pretende, por um lado, dar conta da realidade sociocultural daqueles alunos de Português Língua Não-Materna, e, por outro, visa refletir sobre a aquisição/ aprendizagem da competência pragmática por parte destes sujeitos, falantes de herança, através da realização que fazem de atos ilocutórios diretivos – de pedido e de ordem –, bem como, sobre o grau de formalização das expressões de delicadeza que fazem. Por conseguinte, elaborámos uma Ficha Sociolinguística para recolha de dados referentes ao contexto familiar, sociocultural e linguístico dos alunos. Posteriormente, elaborámos e aplicámos um teste linguístico, de Tarefas de Elicitação do Discurso, com vista à recolha de dados para a construção de um corpus linguístico que nos permitisse desenvolver o presente estudo. A aplicação do teste linguístico e consequente tratamento dos dados recolhidos revelaram que as escolhas pragmáticas dos sujeitos são condicionadas pelo contexto sociocultural e linguístico em que estão imersos. Constatámos, igualmente, que a generalidade dos alunos recorre a duas estratégias de mitigação do discurso, pelo uso de duas expressões de delicadeza: a fórmula «se faz favor»/«por favor» e o verbo modal «poder».

THE ROLE OF RULES, EXAMPLES AND INDIVIDUAL DIFFERENCES IN THE ACQUISITION OF DECLARATIVE AND PROCEDURAL SECOND LANGUAGE KNOWLEDGE

The relevance of explicit instruction has been well documented in SLA research. Despite numerous positive findings, however, the issue continues to engage scholars worldwide. One issue that was largely neglected in previous empirical studies - and one that may be crucial for the effectiveness of explicit instruction - is the timing and integration of rules and practice. The present study investigated the extent to which grammar explanation (GE) before practice, grammar explanation during practice, and individual differences impact the acquisition of L2 declarative and procedural knowledge of two grammatical structures in Spanish. In this experiment, 128 English-speaking learners of Spanish were randomly assigned to four experimental treatments and completed comprehension-based task-essential practice for interpreting object-verb (OV) and ser/estar (SER) sentences in Spanish. Results confirmed the predicted importance of timing of GE: participants who received GE during practice were more likely to develop and retain their knowledge successfully. Results further revealed that the various combinations of rules and practice posed differential task demands on the learners and consequently drew on language aptitude and WM to a different extent. Since these correlations between individual differences and learning outcomes were the least observed in the conditions that received GE during practice, we argue that the suitable integration of rules and practice ameliorated task demands, reducing the burden on the learner, and accordingly mitigated the role of participants’ individual differences. Finally, some evidence also showed that the comprehension practice that participants received for the two structures was not sufficient for the formation of solid productive knowledge, but was more effective for the OV than for the SER construction.

Identification of telomere dysfunction in Friedreich ataxia.

Background: Friedreich ataxia (FRDA) is a progressive inherited neurodegenerative disorder caused by mutation of the FXN gene, resulting in decreased frataxin expression, mitochondrial dysfunction and oxidative stress. A recent study has identified shorter telomeres in FRDA patient leukocytes as a possible disease biomarker. Results: Here we aimed to investigate both telomere structure and function in FRDA cells. Our results confirmed telomere shortening in FRDA patient leukocytes and identified similar telomere shortening in FRDA patient autopsy cerebellar tissues. However, FRDA fibroblasts showed significantly longer telomeres at early passage, occurring in the absence of telomerase activity, but with activation of an alternative lengthening of telomeres (ALT)-like mechanism. These cells also showed accelerated telomere shortening as population doubling increases. Furthermore, telomere dysfunction-induced foci (TIF) analysis revealed that FRDA fibroblasts have dysfunctional telomeres. Conclusions: Our finding of dysfunctional telomeres in FRDA cells provides further insight into FRDA molecular disease mechanisms, which may have implications for future FRDA therapy.

Significati particolari di ἀπάτη e ἀπατάω nel greco koiné e l’interpretazione di ἀπατῶν καρδίαν αὐτοῦ in Gc 1,26

L.T. Johnson ha interpretado ἀπατῶν καρδίαν αὐτοῦ in Sant 1,26 como “indulging his heart”. La propuesta requiere una revisión de los casos en los que ἀπάτη y ἀπατάω tienen un significado diferente del original “engaño” / “engañar” en varias fuentes antiguas. La investigación ha conducido a la identificación de tres significados del verbo y del nombre, todos ellos relacionados con la semántica del placer y la diversión. En Sant 1:26 podemos admitir el significado de “dar placer” para ἀπατάω. Llegamos a la conclusión, sin embargo, que esta interpretación es muy poco probable y es preferible dar a ἀπατάω el sentido de “engañar”.

Image summarisation: human action description from static images

Dissertação de Mestrado, Processamento de Linguagem Natural e Indústrias da Língua, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2014

Richard Serra

Dissertação de Mestrado para obtenção do grau de Mestre em Design de Moda, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

Notas sobre la lengua guaymí en Costa Rica

Como aproximación panorámica al estudio actual del guaymí, una de las lenguas de la familia chibcha, es un análisis introductorio de los rasgos gramaticales y tipológicos generales de esa lengua. Previa información de índole antropológica e histórico-cultural, se exponen en forma analítica aspectos sintácticos, sobre la frase verbal, el morfema de negación, el de reflexivización, los sujetos dativos, los objetos directos. Señala algunas tareas pendientes, que suponen un estudio más pormenorizado y extendido.Providing a panoramic view of the present studies of the Guaymí language, one of the Chibchan languages, this is an introductory analysis of the general grammatical and typological features of that language. First, information is given on anthropological, historical and cultural aspects. Then syntactic features are described for the verb phrase, the morpheme for negation, reflexive forms, dative subjects and direct objects. Mention is made of pending tasks requiring a broader and more detailed study.

Assigning Refugees to Landlords in Sweden: Stable Maximum Matchings

This version: August 15, 2017 (original version: December 7, 2016)

Prevalence of hepatitis E virus antibodies in workers occupationally exposed to swine in Portugal

The concept of zoonotic hepatitis E in industrialized countries has emerged with the discovery of swine strains of hepatitis E virus (HEV) genotype 3, closely related to human HEV. Different routes of zoonotic HEV transmission have been recognized, including contact with infected pigs. Workers occupationally exposed to swine (WOES) have been considered a risk group for HEV infection, but contradictory results have been reported. In the present study, we searched for anti-HEV IgG in WOES (butchers, slaughterhouse workers, veterinarians and pig farmers; n = 114) and in the general population (n = 804) in order to investigate the potential occupational risk of zoonotic HEV infection in this work group. A significantly higher (p = 0.008) anti-HEV IgG seroprevalence was found in WOES (30.7 %) when compared with the general population (19.9 %). Multivariate analysis showed that having professions with exposure to pigs for more than 16.5 years was a risk factor for being positive for anti-HEV IgG (aOR of 5.4, 95 % CI 1.9-15.6, p = 0.002). To our knowledge, this is the first study on the prevalence of anti-HEV IgG in WOES in Portugal, also showing increased probability for infection in this group.