WNT Signaling in Drosophila Neuromuscular Junctions

The Wnt -Wingless (Wg) in Drosophila- signaling is an evolutionary conserved, fundamental signal transduction pathway in animals, having a crucial role in early developmental processes. In the adult animal the Wnt cascade is mainly shut off; aberrant activation leads to cancer. One physiological exception in the adult animal is the activation of Wnt signaling in the nervous system. In the present work, we investigated Wg signaling in the Drosophila neuromuscular junctions (NMJs). The fly NMJs closely resemble the glutamatergic synapses in the mammalian central nervous system and serves as a model system to investigate the mechanism of synapse formation and stability. We demonstrate that the trimeric G-protein Go has a fundamental role in the presynaptic cell in the NMJ. It is implicated in the presynaptic Wg pathway, acting downstream of the ligand Wg and its receptor Frizzled2 (Fz2). Furthermore, we prove that the presynaptic Wg-Fz2-Gαo pathway is essential for correct NMJ formation. The neuronal protein Ankyrin2 (Ank2) localizes to the NMJ and has so far been considered to be a static player in NMJ formation, linking the plasma membrane to the cytoskeleton. We identify Ank2 as a direct target of Gαo. The physical and genetic interaction of Gαo with Ank2 represents a novel branch of the presynaptic Wg pathway, regulating the microtubule cytoskeleton in NMJ formation, jointly with the previously established Futsch-dependent branch, which controls microtubule stability downstream of the kinase Sgg (the homolog of GSK3ß). We moreover demonstrate that the Gαo-Ankyrin interaction to regulate the cytoskeleton is conserved in mammalian neuronal cells. Our findings therefore provide a novel, universally valid regulation of the cytoskeleton in the nervous system. Aberrant inactivation of the neuronal Wnt pathway is believed to be involved in the pathogenesis of the Aß peptide in Alzheimer's disease (AD). We modeled AD in Drosophila by expressing Aß42 in the nervous system and in the eye. Neuronal expression drastically shortens the life span of the flies. We prove that this effect depends on the expression specifically in glutamatergic neurons. However, Aß42 does not induce any morphological changes in the NMJ; therefore this synapse is not suitable to study the mechanism of Aß42 induced neurotoxicity. We furthermore demonstrate that genetic activation of the Wnt pathway does not rescue the Aß42 induced phenotypes - in opposition to the dominating view in the field. These results advice caution when interpreting data on the potential interaction of Wnt signaling and AD in other models. -- La voie de signalisation Wnt (Wingless (Wg) chez la drosophile) est conservée dans l'évolution et fondamentale pour le développement des animaux. Cette signalisation est normalement inactive chez l'animal adulte; une activation anormale peut provoquer le cancer. Or, ceci n'est pas le cas dans le système nerveux des adultes. La présente thèse avait pour but d'analyser le rôle de la voie de signalisation Wingless dans la plaque motrice de Drosophila melanogaster. En effet, cette plaque ressemble fortement aux synapses glutaminergiques du système nerveux central des mammifères et procure ainsi un bon modèle pour l'étude des mécanismes impliqués dans la formation et la stabilisation des synapses. Nos résultats montrent que la protéine trimérique Go joue un rôle fondamental dans la fonction de la cellule présynaptique de la plaque motrice. Go est en effet impliqué dans la voie de signalisation Wg, opérant en aval du ligand Wg et de son récepteur Frizzled2. Nous avons pu démontrer que cette voie de signalisation Wg-Fz2-Gαo est essentielle pour le bon développement et le fonctionnement de la plaque motrice. Fait intéressant, nous avons montré que la protéine neuronale Ankyrin2 (Ank2), qui est connue pour jouer un rôle statique en liant la membrane plasmique au cytosquelette dans la plaque motrice, est une cible directe de Gαo. L'interaction physique et génétique entre Gαo et Ank2 constitue ainsi une bifurcation de la voie de signalisation présynaptique Wg. Cette voie régule le cytosquelette des microtubules en coopération avec la branche liée à la protéine Futsch. Cette protéine est l'homologue de la protéine liant les microtubules MAP1B des mammifères et contrôle la stabilité des microtubules opérant en aval de la kinase Sgg (l'homologue de GSK3ß). De plus, la régulation du cytosquelette par l'interaction entre Gαo et Ankyrin est conservée chez les mammifères. Dans leur ensemble, nos résultats ont permis d'identifier un nouveau mode de régulation du cytosquelette dans le système nerveux, probablement valable de manière universelle. La voie de signalisation Wnt est soupçonnée d'être impliquée dans la toxicité provoquée par le peptide Aß dans le cadre de la maladie d'Alzheimer. Nous avons tenté de modéliser la maladie chez la drosophile en exprimant Aß42 spécifiquement dans le cerveau. Cette expérience a montré que l'expression neuronale d'Aß42 réduit la durée de vie des mouches de manière significative par un mécanisme impliquant les cellules glutamatergiques. Par contre, aucune modification morphologique n'est provoquée par Aß42 dans les plaques motrices glutamatergiques. Ces résultats montrent que ce modèle de Drosophile n'est pas adéquat pour l'étude de la maladie d'Alzheimer. De plus, l'activation génétique de la voie de signalisation Wg n'a pas réussi à restaurer les phénotypes de survie ou ceux des yeux causés par Aß42. Ces résultats indiquent que l'implication de la voie de signalisation Wg dans la maladie d'Alzheimer doit être considérée avec prudence.

Genetic evidence for female-biased dispersal and gene flow in a polygynous primate.

Many models of sex-biased dispersal predict that the direction of sex-bias depends upon a species' mating system. In agreement with this, almost all polygynous mammals show male-biased dispersal whereas largely monogamous birds show female-biased dispersal (FBD). The hamadryas baboon (Papio hamadryas hamadryas) is polygynous and so dispersal is predicted to be male biased, as is found in all other baboon subspecies, but there are conflicting field data showing both female and male dispersal. Using 19 autosomal genetic markers genotyped in baboons from four Saudi Arabian populations, we found strong evidence for FBD in post-dispersal adults but not, as expected, in pre-dispersal infants and young juveniles, when we compared male and female: population structure (F(st)), inbreeding (F(is)), relatedness (r), and the mean assignment index (mAIc). Furthermore, we found evidence for female-biased gene flow as population genetic structure (F(st)), was about four times higher for the paternally inherited Y, than for either autosomal markers or for maternally inherited mtDNA. These results contradict the direction of sex-bias predicted by the mating system and show that FBD has evolved recently from an ancestral state of male-biased dispersal. We suggest that the cost-benefit balance of dispersal to males and females is tightly linked to the unique hierarchical social structure of hamadryas baboons and that dispersal and social organization have coevolved.

Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in human plasma.

Thioridazine is a commonly prescribed phenothiazine drug administered as a racemate and it is believed that its antipsychotic effect is mainly associated with (R)-thioridazine. A method based on high-performance liquid chromatography has been developed for the determination of the enantiomers of thioridazine and thioridazine 2-sulfone (THD 2-SO2 or sulforidazine) and of the enantiomers of the diastereoisomeric pairs of thioridazine 2-sulfoxide (THD 2-SO or mesoridazine) and thioridazine 5-sulfoxide (THD 5-SO) in the plasma of thioridazine-treated patients. The method involves sequential achiral and chiral HPLC. The limits of quantitation for total (R) + (S) concentrations were found to be 15 ng/ml for thioridazine and 5 ng/ml for its metabolites. The limits for the determination of the (R)/(S) ratios were found to be 60 ng/ml for racemic THD and 10 ng/ml for racemic THD 2-SO, THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE). The method has been used to determine the concentrations of the enantiomers of thioridazine and of its metabolites in the plasma of a patient treated with 100 mg of racemic thioridazine hydrochloride per os per day for 14 days. The results show a high enantioselectivity in the metabolism of this drug: the (R)/(S) ratios for THD, THD 2-SO (FE), THD 2-SO (SE), THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE) were found to be 3.90, 1.22, 6.10, 4.10, 0.09 and 28.0, respectively.

Cuando Frankenstein encontró a Dorian Gray: dandysmo, post-identidad y sujetos virtuales

The appearance and popularization of the internet has created new forms of writing, which compel us to think anew about identity and subjectivity. Webjournals or blogs are specially interesting because they are a massive phenomenon that use autobiographical writing in a peculiar way. These forms of writing stress a particular paradox of the genre: the coexistence between a purpose of private, confessional and spontaneous writing and a public image, carefully built, as a result of its writing. The technology is new, but, in fact, the paradox is old. This paper tries to explore this old paradox, our eternal condition of cyborgs, our use of technologies in order to construct a public, unique and recognizably identity. In oder to do so, I will try to show the virtual condition of any written individual ¿this issue has already been dealt with by autobiographical studies¿, focusing on blogs, and especially on concrete example (Lord Whimsy¿s Journal). I will pay attention to gender as a technology that constructs identity and, at the same time, is deconstructed by the autobiographical narratives analyzed. In short, I attempt to show that virtual and autobiographical discourse do not bring forth a new kind of subject but the permanence of an old phenomenon "clearly developed by dandyism, for instance¿: the use of tehnologies to re-invent, re-formulate and re-construct us as multiple, hybrid and mixed subjects."

Flight, feeding and reproductive behavior of Phyllophaga cuyabana (Moser) (Coleoptera: Melolonthidae) adults

Phyllophaga cuyabana is a univoltine species and its development occurs completely underground. Its control by conventional methods, such as chemical and biological insecticides, is difficult, so it is important to understand its dispersion, reproduction, and population behavior in order to determine best pest management strategies. The objective of this work was to study the behavior of adults of P. cuyabana. This study was carried out in the laboratory, greenhouse and field sites in Paraná State, Brazil (24º25' S and 52º48' W), during four seasons. The results obtained demonstrate that: a) P. cuyabana adults have a synchronized short-flight period when mating and reproduction occurs; b) adults tend to aggregate in specific sites for mating; c) the majority of adults left the soil on alternate nights; d) the choice of mating and oviposition sites was made by females before copulation, since after copulation adults did not fly from or bury themselves at nearby locations; e) females that fed on leaves after mating, oviposited more eggs than females that had not fed;f) plant species such as sunflower (Helianthus annuus) and the Crotalaria juncea are important food sources for adults.

El doblatge d’una comèdia britànica: The Vicar of Dibley

Aquest treball analitza els problemes de doblatge de l’anglès al català que presenta una sèrie còmica, The Vicar of Dibley. L’objectiu es estudiar tant problemes generals com específics per tal de demostrar la viabilitat del doblatge d’aquesta comèdia. Es proposen possibles solucions per a tots els problemes analitzats.

El futbol femení a Osona: desigualtats, necessitats, demanda i potencialitat d'un campus de futbol per a noies de la comarca

L’objectiu d’aquest treball és determinar si existeix una desigualtat entre el futbol femení i el masculí en esdeveniments esportius i en el seu cas realitzar propostes ajustades a les necessitats actuals. D’una banda, les dades cedides per la Federació Catalana de Futbol permeten comparar l’evolució de futbolistes federats i federades i certifiquen que hi ha un canvi de socialització de la dona dins de l’esport, concretament, del futbol osonenc. D’altra banda, de la literatura es desprèn que és possible detectar que la progressió de la dona en l’esport no va d’acord amb les necessitats d’aquest gènere. És per això, que mitjançant la tècnica de treball dels grups de discussió, integrats per jugadores, entrenadors i pares i mares, ens acostarem a la realitat per tal d’esbrinar la demanda d’un possible campus de futbol femení; els seus objectius i les preferències d’aquest col·lectiu per aconseguir satisfer les seves necessitats.

Participació i associacionisme de les dones a Vic

L’objectiu d’aquest treball és visibilitzar la participació de les dones a la ciutat de Vic, per tal de reconèixer el seu paper dins la societat. Aquest treball pretén doncs, ressaltar una presència visible i empoderada de les dones dins les associacions i, també, un canvi de mirada que permeti veure les dones com a protagonistes de canvis i transformacions. La divisió tradicional del treball va confinar la dona a l’espai privat, de manera que l’allunyà de la participació política, institucional i social de la vida. L’aportació del moviment associatiu femení ha estat clau, i la influència que ha exercit en les conquestes socials és evident. Com a producte final i per tal de donar evidència de la participació de les dones a la ciutat, adjunto un llibret on es pot trobar totes les associacions de dones que hi ha Vic, amb la seva fitxa tècnica pertinent i la mirada d’algunes de les dones que participen activament d’aquest associacionisme femení.

Rethinking study and management of agricultural systems for policy design

There is a concern that agriculture will no longer be able to meet, on a global scale, the growing demand for food. Facing such a challenge requires new patterns of thinking in the context of complexity and sustainability sciences. This paper, focused on the social dimension of the study and management of agricultural systems, suggests that rethinking the study of agricultural systems entails analyzing them as complex socio-ecological systems, as well as considering the differing thinking patterns of diverse stakeholders. The intersubjective nature of knowledge, as studied by different philosophical schools, needs to be better integrated into the study and management of agricultural systems than it is done so far, forcing us to accept that there are no simplistic solutions, and to seek a better understanding of the social dimension of agriculture. Different agriculture related problems require different policy and institutional approaches. Finally, the intersubjective nature of knowledge asks for the visualization of different framings and the power relations taking place in the decision-making process. Rethinking management of agricultural systems implies that policy making should be shaped by different principles: learning, flexibility, adaptation, scale-matching, participation, diversity enhancement and precaution hold the promise to significantly improve current standard management procedures.

Salmonella epidural abscess in sickle cell disease: failure of the nonsurgical treatment.

In patients suffering from sickle cell disease (SCD), bone is a preferred site of infection. We report the case of a five-year-and-eight-month-old black African boy with homozygous-SS disease who developed a cranial epidural abscess. This intracranial infectious complication originated from a Salmonella enteritidis osteitis of the frontal bone. Antibiotic treatment alone did not control the disease, so surgery was necessary to remove the necrotic bone and to evacuate the epidural pus. The numerous factors interfering with normal healing of a septic focus in sickle cell anemia, particularly in this previously undescribed intracranial complication, emphasize the need for a primary and early surgical treatment in similar situations.

Pinpointing Suspect Triplicate Unconfined Compressive Strength Values in a Series of Soil-Additive Strength Determinations, HR-1, Progress Report, 1961

In recent years, various types of organic and inorganic materials have been investigated for use as soil stabilizing agents in the construction of highways and airports. Since the properties and environmental conditions of soils vary so greatly from place to place, a stabilizing agent that is suitable for one type of soil may not be satisfactory for another. As a result, it is often desirable to evaluate several stabilizing agents under varying treatment conditions before deciding on a specific one to be used with a given soil. In addition many research programs have been initiated which investigate the effects of these stabilizing agents upon soils.

Holism and structural realism

We first introduce structural realism as a position in the metaphysics of science, pointing out the way in which this position replaces intrinsic properties with relations so that it amounts to a holistic in contrast to an atomistic metaphysics. We argue in favour of a moderate version of structural realism that puts objects and relations on the same ontological footing and assess the general philosophical arguments for this position. The second section shows how structural realism gains support from quantum physics. The third section explains how structural realism can be applied to the metaphysics of space-time.

¿Una xarxa global de moviments socials? Una aproximació al cicle de protestes 2011-2013

Les protestes socials esdevingudes en nombrosos països durant els últims tres anys –des de Tunísia i l’anomenada “Primavera àrab” fins a les recents mobilitzacions a Turquia o Brasil– han fet aflorar un debat sobre la possible dimensió global i transestatal de totes elles. El present article pretén realitzar una aproximació descriptiva i analítica a aquest intens cicle de protestes, reflexionant sobre les diferències i similituds existents entre elles, el paper que Internet i les xarxes socials han tingut en el curs de les diferents mobilitzacions o, entre altres aspectes, el repertori d’accions que han emprat. Més enllà d’aquests trets compartits o no, l’article mira d’emfasitzar la importància d’entendre aquest cicle de mobilitzacions com un procés de repolitització social que combina les contradiccions i conflictes locals de cada context en particular amb l’aparent existència d’una demanda global per major democratització política, regeneració institucional, justícia social i reapropiació d’allò comú.

The handaxe and the microscope: individual and social learning in a multidimensional model of adaptation

When individuals learn by trial-and-error, they perform randomly chosen actions and then reinforce those actions that led to a high payoff. However, individuals do not always have to physically perform an action in order to evaluate its consequences. Rather, they may be able to mentally simulate actions and their consequences without actually performing them. Such fictitious learners can select actions with high payoffs without making long chains of trial-and-error learning. Here, we analyze the evolution of an n-dimensional cultural trait (or artifact) by learning, in a payoff landscape with a single optimum. We derive the stochastic learning dynamics of the distance to the optimum in trait space when choice between alternative artifacts follows the standard logit choice rule. We show that for both trial-and-error and fictitious learners, the learning dynamics stabilize at an approximate distance of root n/(2 lambda(e)) away from the optimum, where lambda(e) is an effective learning performance parameter depending on the learning rule under scrutiny. Individual learners are thus unlikely to reach the optimum when traits are complex (n large), and so face a barrier to further improvement of the artifact. We show, however, that this barrier can be significantly reduced in a large population of learners performing payoff-biased social learning, in which case lambda(e) becomes proportional to population size. Overall, our results illustrate the effects of errors in learning, levels of cognition, and population size for the evolution of complex cultural traits. (C) 2013 Elsevier Inc. All rights reserved.

Holism and structural realism

We first introduce structural realism as a position in the metaphysics of science, pointing out the way in which this position replaces intrinsic properties with relations so that it amounts to a holistic in contrast to an atomistic metaphysics. We argue in favour of a moderate version of structural realism that puts objects and relations on the same ontological footing and assess the general philosophical arguments for this position. The second section shows how structural realism gains support from quantum physics. The third section explains how structural realism can be applied to the metaphysics of space-time.