1,721,022 research outputs found
ENDOGENOUS LIPID PEROXIDATION PRODUCT 9-HSA REGULATES PROGENITOR FATE IN THE VERTEBRATE RETINA
No full textNeurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease).
Full text linkThe neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80-85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery
Fonction des Meteorins dans le guidage des axones commissuraux et leur rôle en tant que nouveaux régulateurs de la configuration gauche-droite dans l'embryon de poisson zèbre
No full textL'un des principaux objectifs de la neurobiologie du développement est de comprendre comment les axones des neurones nouveau-nés peuvent atteindre leurs partenaires synaptiques corrects en suivant des chemins précis et bien définis, guidés par un réseau complexe d'interactions récepteur/ligand (par exemple, netrin/DCC ; slit/robo). Bien qu'un grand nombre de molécules de guidage axonal ait déjà été caractérisé, le tableau est loin d'être complet et un certain nombre de facteurs de guidage restent à découvrir. Les travaux précédents du laboratoire ont généré des allèles de perte de fonction pour les trois gènes du poisson zèbre de la famille des protéines sécrétées Meteorin (Metrn). De façon remarquable, nous avons pu caractériser des défauts de développement axonal spécifiques chez ces poissons mutants, y compris des défauts dans plusieurs populations de neurones commissuraux. Soutenus par nos résultats préliminaires, nous avons émis l'hypothèse que les Metrn jouent un rôle important au cours du développement du SNC des vertébrés et du franchissement de la ligne médiane axonale, en particulier dans le guidage des axones commissuraux. Par conséquent, l'objectif de mon projet de doctorat est d'étudier la fonction des Metrn chez le poisson zèbre, d'élucider leurs voies de signalisation biochimique et, surtout, d'identifier le ou les récepteurs encore inconnus. Metrn a d'abord été découvert comme un facteur neurotrophique sécrété qui favorise la croissance des neurites in vitro. Il est exprimé dans les progéniteurs neuronaux radiaux et la glie radiale. Chez les vertébrés, les Metrn sont hautement conservés et comprennent deux membres chez les mammifères et trois chez le poisson zèbre (Metrn, Metrnl1 et Metrnl2). Chaque gène Metrn ou Metrnl code pour une protéine d'environ 300 acides aminés contenant une séquence signal N-terminale ainsi qu'un domaine de type Netrin à l'extrémité C-terminale. Une partie de mon projet de thèse consistait à évaluer la localisation des protéines Metrn in vivo et à caractériser leur activité sur le développement des axones commissuraux chez le poisson zèbre. Dans ce but, j'ai réalisé des hybridations in situ en double fluorescence pour comparer les expressions de metrn et metrnl1 à l'expression du facteur de guidage axonal bien établi Slit. Les résultats ont montré que metrn et metrnl1 sont co-localisés avec slit1a, slit1b et slit2 au niveau de la plaque de plancher à 2dpf. J'ai également validé la conservation de ce modèle d'expression chez la souris. Cette colocalisation soutient le rôle des Metrns comme nouveaux acteurs dans le guidage axonal le long des Slits et d'autres facteurs impliqués dans ce processus. Par le biais de la qPCR et de l'hybridation in situ, j'ai découvert non seulement que les facteurs nodaux étaient significativement altérés chez les mutants triple metrn, mais aussi que chez le poisson zèbre de type sauvage, en particulier metrnl1 est exprimé plus tôt que prévu (avant 6hpf). De plus, j'ai observé des mouvements aléatoires ou symétriques du cœur et des boucles chez les mutants triples, similaires à ceux décrits chez les mutants spaw et lefty. Ensemble, ces observations soulèvent l'hypothèse que les Metrns pourraient également interagir avec les facteurs Nodal et jouer un rôle dans le patterning gauche-droite.One of the major goals of developmental neurobiology is to understand how axons of newborn neurons can reach their correct synaptic partners by following precise and well-defined paths guided by a complex network of receptor/ligand interactions (e.g. netrin/DCC; slit/robo) Although a big set of axon guidance molecules has been already characterized, the whole picture is far from being complete and a number of guidance factors still remain to be discovered. Previous work in the laboratory has generated loss-of-function alleles for all three zebrafish genes from the Meteorin (Metrn) family of secreted proteins. Remarkably, we could characterize specific axonal development defects in these mutant fish including defects in several commissural neuron populations. Supported by our preliminary results, we hypothesized that Metrns play an important role during the development of the vertebrate CNS and axonal midline crossing, especially in commissural axon guidance. Therefore, the goal of my PhD project is to investigate the function of Metrns in zebrafish, to elucidate their biochemical signaling pathways, and, most notably, to identify the as-yet-unknown receptor(s). Metrn was first discovered as a secreted neurotrophic factor which promotes neurite outgrowth in vitro. It is expressed in radial neuronal progenitors and radial glia. In vertebrates Metrns are highly conserved including two members in mammals and three in zebrafish (Metrn, Metrnl1 and Metrnl2). Each Metrn or Metrnl gene codes for a protein of around 300 amino acids containing an N-terminal signal sequence as well as a Netrin-like domain at the C-terminus. One part of my PhD project was to evaluate the Metrns protein localization in vivo and characterize their activity on commissural axons development in zebrafish. With this intent, I performed double fluorescence in situ hybridizations to compare the expressions of metrn and metrnl1 to the expression of the well-established axonal guidance factor Slit. The results showed that metrn and metrnl1 co-localizes with slit1a, slit1b and slit2 at the floorplate at 2dpf. I further validated the conservation of this expression pattern in mouse. This colocalization supports the role of Metrns as novel players in axonal guidance along Slits and other factors implicated in this process. Furthermore, it has been reported that nodal, lefty as well p-smad2 expression is downregulated in Meteorin-null ES-cells.Via qPCR and in situ hybridization I discovered not only that Nodal factors were significantly altered in triple metrn mutants but also that in wild-type zebrafish, especially metrnl1 is expressed earlier than previously assumed (earlier than 6hpf). Additionally, I observed randomized or symmetric heart jogging and looping in triple mutants, similar to the ones described in spaw and lefty mutants. Together, these observations raise the hypothesis that Metrns also could interact with Nodal factors and could play a role in the left-right patterning
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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