Post-traumatic Winking Induced by Extension of the Hand: A Case Report of a Novel Synkinesis

Several synkinesis syndromes have been reported in the literature. Synkinesis syndromes are rare and are most commonly congenital or follow post-traumatic reinnervation. We describe a novel synkinesis syndrome that developed several months after cervical spinal cord infarction due to a herniated disc in a 29-year-old woman. When the patient overstretched the extensor muscles of the right hand, the right upper eyelid raised automatically and nasal congestion developed. We hypothesize that aberrant reinnervation of the intermediolateral columns of the spinal cord at level C8–T2 by motor neurons of the extensor muscles of the hand occurred.

The negation of the other in the novel Sula by Toni Morrison [recurso electr?nico]

This analysis corresponds to an analytical and interpretative essay on the negation of the other in the novel Sula (1973) by Toni Morrison, one of the most important African American writers. In Sula, the author explores the concepts of good and evil as she provides characteristics of the African American culture and black identity. The characters? main struggle is their quest for achieving an authentic identity within this sexist and racist society that constricts their lives and dreams with moral standards. This essay attempts to demonstrate through this novel how human beings find self-destruction by attempting to destroy others, those who have different views of life and the world. The analysis focuses on the most important aspects of life proposed in this book: self-awareness, identity, friendship, traveling, the community, and heritage, which condition one?s vision towards the other and nurture, at the same time, one?s whole identity. As a major conclusion, there is no success for a society that judges and isolates the individuals who want to become authentic and attempt to break the constrictions of moral prejudices. For each member of the community is essential in the balance of it.

An investigation into the folding and assembly of engineered antibodies and novel antibody formats

Monoclonal antibodies and novel antibody formats are currently one of the principal therapeutic in the biopharmaceutical industry worldwide and are widely used in the treatment of autoimmune diseases and cancer. It is for this reason that the productivity and quality of antibody production requires improvement; specifically investigations into the engineering of antibodies and any issues that may arise from the production of these therapeutics. The work presented in this thesis describes an investigation into the folding and assembly of seven antibodies plus the novel antibody format FabFv. IgG is comprised of two identical HCs and two identical LCs. The folding process of immunoglobulin is controlled by the CH1 domain within the HC. The CH1 domain remains in a disordered state and is sequestered by BiP in the endoplasmic reticulum. Upon the addition of a folded CL domain, BiP is displaced, the CH1 domain is able to fold and the complete IgG protein can then be secreted from the cell. The results presented in this thesis however, have outlined an additional mechanism for the folding of the CH1 domain. We have shown that the CH1 domain is able to fold in the absence of LC resulting in the secretion of HC dimers in a VH dependent manner. The proposed mechanism for the secretion of HC dimers suggests that some VH domains can interact with each other in order to bring the CH1 domains in close proximity to enable folding to occur. As HC dimer secretion is a hindrance in antibody production, this result has highlighted an engineering target to improve antibody yield. Examination of the folding of IgG4 with the variable region A33 has revealed the inability to secrete LC dimers, cleavage of the HC during expression and secretion of HC dimers in the Fab, FabFv and full length forms. The attributes described have also been shown to be variable region dependent. This has introduced a new concept that the variable domain is important in determining the expression and secretion of antibodies and their individual chains. Pulse chase and 2D gel electrophoresis analysis of the novel antibody format FabFv has revealed that the folding and expression of the LC and HC causes multimeric species of FabFv to be secreted, as opposed to the monomeric form which is the desired therapeutic. Our hypothesis is that this process occurs via a LC dependent mechanism. The proposed hypothesis suggests that further engineering to the LC could diminish the formation and secretion of FabFv multimers. The results from these investigations can be applied to increase the productivity of therapeutics and increase the biological understanding of the domain interactions of IgG during folding, assembly and secretion.

FAM49 - A novel regulator of the protrusive behaviour and motility of cells

Most eukaryotic cell motility relies on plasma membrane protrusions, which depend on the actin cytoskeleton and its tight regulation. The SCAR/WAVE complex, a pentameric assembly comprising SCAR/WAVE, Nap1, CYFIP/Pir121, Abi and HSPC300, is a key driver of actin-based protrusions such as pseudopods. SCAR/WAVE is thought to activate the Arp2/3 complex, a crucial actin nucleator, after being itself activated by upstream signals such as active Rac1. Despite recent progress on the study of the SCAR/WAVE complex, its regulation is still incompletely understood, with Nap1’s role being particularly enigmatic. Upon screening for potential Nap1 binding partners in the social amoeba Dictyostelium discoideum – a well established model organism in the study of the actin cytoskeleton and cell motility – we found FAM49, a ~36 kDa protein of unknown function which is highly conserved in Metazoa (animals) and evolutionarily closer species such as D. discoideum. Interestingly, D. discoideum’s FAM49 and its homologs contain a DUF1394 domain, which is also predicted in CYFIP/Pir121 proteins and most likely involved in their direct binding to active Rac1, which in turn contributes to SCAR/WAVE’s activation. FAM49’s unknown role, apparent high degree of conservation and potential connections to SCAR/WAVE and Rac1 persuaded us to start investigating its function and biological relevance in D. discoideum, leading to the work presented in this thesis. Several pieces of our data collectively support a function for FAM49 in modulating the protrusive behaviour, and ultimately motility, of D. discoideum cells, as well as a regulatory link between FAM49 and Rac1. FAM49’s involvement in protrusion regulation was first hinted at by our observation that GFP-tagged FAM49 is enriched in pseudopods. The possibility of a link with Rac1 was then strengthened by two additional observations: first, pseudopodial GFP-FAM49 is substantially co-enriched with active Rac, both showing fairly comparable spatio-temporal accumulation dynamics; second, when dominant-active (G12V) Rac1 is expressed in cells, it triggers the recruitment and persistent accumulation of GFP-FAM49 at the plasma membrane, where both become highly co-enriched. We subsequently determined that fam49 KO cells differ from wild-type cells in the way they protrude and move, as assessed in under-agarose chemotaxis assays. In particular, our data indicate that fam49 KO cells tend to display a lower degree of global protrusive activity, their protrusions extend more slowly and are less discrete, and the cells end up moving at lower speeds and with higher directional persistence. This phenotype was substantially rescued by FAM49 re-expression. While re-expressing FAM49 in fam49 KO cells we generated putative FAM49 overexpressor cells; compared to wild-type cells, they displayed atypically thin pseudopods and what seemed to be an excessively dynamic, and perhaps less coordinated, protrusive behaviour. Additional data in our study suggest that pseudopods made by fam49 KO cells are still driven by SCAR/WAVE, which is clearly not being replaced by WASP (as is now known to be the case in D. discoideum cells lacking a functional SCAR/WAVE complex). Nonetheless, the peculiar dynamics of those pseudopods imply that SCAR/WAVE’s activity is regulated differently when FAM49 is lost, though it remains to be determined how. This thesis is the first report of a dedicated study on FAM49 and lays the foundation for future research on it.

Shakespeare at the Festival d'Avignon : the Poetics of Adaptation of L. Lagarde (Richard III, 2007), T. Ostermeier (Hamlet, 2008) and I. van Hove (The Roman Tragedies, 2008)

International audience

Design and validation of a novel generic platform for the production of tetravalent IgG1-like bispecific antibodies

International audience

Forms of the Postmodern Historical Novel : Christoph Ransmayr, Daniel Kehlmann, Wolfgang Hildesheimer

L’émergence du postmodernisme aux Etats-unis, mouvement esthétique rejetant les dogmes modernistes, date des années 1960. En s’imposant, durant les dernières décennies du 20ème siècle, comme le paradigme esthétique de l’architecture, des arts et de la littérature, le postmodernisme a également créé les conditions propres à une renaissance du roman historique. Cependant, la fiction historique postmoderne constitue maintenant une nouvelle forme du genre basée sur la parodie, l’ironie et le scepticisme envers les discours dominants. Cette nouvelle forme ne se limite plus à la présentation des récits dans un cadre historique réaliste. Elle remet plutôt en question la validité et par conséquent la nature même du discours historique, problématisant et mettant ainsi à l’avant le processus d’interprétation et de reconstruction du passé. Dans cette optique, la fiction historique contemporaine reflète les débats actuels sur les formes de l’historiographie, débats lancés par Hayden White. Dans les années 1980, la fiction historique a de nouveau fleuri dans l'espace culturel allemand tout comme ailleurs. Le présent mémoire analyse des formes postmodernes de la fiction historique en se basant sur trois romans historiques de langue allemande parus entre 1981 et 2005: Die Schrecken des Eises und der Finsternis de Christoph Ransmayr, Die Vermessung der Welt de Daniel Kehlmann et Marbot : Eine Biographie de Wolfgang Hildesheimer. L’analyse s'appuie sur divers modèles de la fiction postmoderne, en particulier sur le schéma de catégorisation du roman historique élaboré par Ansgar Nünning. Le mémoire montre dans quelle mesure ces romans appliquent des moyens stylistiques typiques pour le postmodernisme et portent un regard critique ou comique sur l’histoire et la culture allemande et autrichienne.

Forms of the Postmodern Historical Novel : Christoph Ransmayr, Daniel Kehlmann, Wolfgang Hildesheimer

L’émergence du postmodernisme aux Etats-unis, mouvement esthétique rejetant les dogmes modernistes, date des années 1960. En s’imposant, durant les dernières décennies du 20ème siècle, comme le paradigme esthétique de l’architecture, des arts et de la littérature, le postmodernisme a également créé les conditions propres à une renaissance du roman historique. Cependant, la fiction historique postmoderne constitue maintenant une nouvelle forme du genre basée sur la parodie, l’ironie et le scepticisme envers les discours dominants. Cette nouvelle forme ne se limite plus à la présentation des récits dans un cadre historique réaliste. Elle remet plutôt en question la validité et par conséquent la nature même du discours historique, problématisant et mettant ainsi à l’avant le processus d’interprétation et de reconstruction du passé. Dans cette optique, la fiction historique contemporaine reflète les débats actuels sur les formes de l’historiographie, débats lancés par Hayden White. Dans les années 1980, la fiction historique a de nouveau fleuri dans l'espace culturel allemand tout comme ailleurs. Le présent mémoire analyse des formes postmodernes de la fiction historique en se basant sur trois romans historiques de langue allemande parus entre 1981 et 2005: Die Schrecken des Eises und der Finsternis de Christoph Ransmayr, Die Vermessung der Welt de Daniel Kehlmann et Marbot : Eine Biographie de Wolfgang Hildesheimer. L’analyse s'appuie sur divers modèles de la fiction postmoderne, en particulier sur le schéma de catégorisation du roman historique élaboré par Ansgar Nünning. Le mémoire montre dans quelle mesure ces romans appliquent des moyens stylistiques typiques pour le postmodernisme et portent un regard critique ou comique sur l’histoire et la culture allemande et autrichienne.

A novel non-peptidic agonist of the ghrelin receptor with orexigenic activity in vivo

Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.

Development of a novel molecular tool for the rapid assessment of the biodiversity changes of benthic nematodes assemblages. Mares Conference Marine Ecosystems Helath and conservation

The molecular profiling system was developed using directed terminal-restriction fragment length polymorphism (dT-RFLP) to characterize soil nematode assemblages by relative abundance of feeding guilds and validation by comparison to traditional morphological method. The good performance of these molecular tools applied to soil nematodes assemblages create an opportunity to develop a novel approach for rapid assessment of the biodiversity changes of benthic nematodes assemblages of marine and estuarine sediments. The main aim of this research is to combine morphological and molecular analysis of estuarine nematodes assemblages, to establish a tool for fast assessment of the biodiversity changes within habitat recovery of Zostera noltii seagrass beds; and validate the dT-RFLP as a high-throughput tool to assess the system recovery. It was also proposed to develop a database of sequences related to individuals identified at species level to develop a new taxonomic reference system. A molecular phylogenetic analysis of the estuarine nematodes has being performed. After morphological identification, barcoding of 18S rDNA are being determined for each nematode species and the results have shown a good degree of concordance between traditional morphology-based identification and DNA sequences. The digest strategy developed for soil nematodes is not suitable for marine nematodes. Then five samples were cloned and sequenced and the sequence data was used to design a new dT-RFLP strategy to adapt this tool to marine assemblages. Several solutions were presented by DRAT and tested empirically to select the solution that cuts most efficiently, separating the different clusters. The results of quantitative PCR showed differences in nematode density between two sampling stations according the abundance of the nematode density obtained by the traditional methods. These results suggest that qPCR could be a robust tool for enumeration of nematode abundance, saving time.

Molecular characterization of Grapevine enamolike virus, a novel putative member of the genus Enamovirus.

2016

Molecular characterization of grapevine enamo-like virus, a novel putative member of the genus enamovirus.

2016

The flower on the street or the light in the swamp: similarities between the poetics of Bueno de Rivera and Drummond

Considering the controversial question of influence, discussed by Harold Bloom, and the reliever concept of poetic membership, proposed by Joao Cabral de Melo Neto, this article aims to show how the poets belonging to the generation of 1945 of Brazilian modernism are characterized by membership with the work of an older poet. We will show this relation in the study of the work of two poets: Drummond, who, according Silviano Santiago, would be the most representative poet of the twentieth century, and Bueno de Rivera, whose work shows a significant similarity of themes and images with the work of the first - which, as noted in this article, is not an indicator of lack of originality. Accordingly, we will reiterate the importance of Drummond’s work and will propose the rescue of Rivera's poetry, somehow forgotten by literary criticism, showing the points of contact between the works of those two poets in relation to the poet's anguish by being-in-world, characteristic of modernity crisis experienced by both, and approached in his works.

CULTURAL CANNIBALISM: A TURNING POINT IN THE PROPOSITION OF AMBIVALENT POETICS IN THE LATIN AMERICAN LITERARY DISCOURSE

The concept of cultural cannibalism was discussed and re-established by intellectuals from the field of literary and cultural criticism, and it was also the object of creative appropriation by a significant group of writers in Brazil and in the Latin America context. Nevertheless, this concept is revitalized in the contemporary context, reflecting the critical consciousness of the writer on the understanding of social inequalities that shape Latin America, in its different segments, be they political, economic or cultural.