1,720,962 research outputs found
Evaluation of neuroprotective effects of sigma 1 receptor ligands on motoneuron degeneration models
Get PDFLes malalties de les motoneurones (MMN) són un conjunt ampli de trastorns neurològics esporàdics i hereditaris caracteritzats per la degeneració d’aquest tipus de neurones, les motoneurones (MN), amb afeccions molt debilitants i greus amb opcions terapèutiques limitades. L’esclerosi lateral amiotròfica (ELA), la MNN més freqüent en adults, és una malaltia neurodegenerativa fatal que cursa amb la degeneració de les MNs de la medul·la espinal i del cervell. Actualment, els tractaments disponibles tenen lleus millores sobre la supervivència del pacient allargant la vida uns mesos. Per tant, és urgent comprendre els mecanismes moleculars implicats en la degeneració de les MNs per identificar noves dianes terapèutiques i desenvolupar teràpies efectives que protegeixin i restaurin la integritat neuronal. Recentment, entre d’altres dianes terapèutiques proposades per la neuroprotecció, el receptor Sigma-1 (Sig-1R) ha guanyat interès. L’objectiu d’aquesta tesi era avaluar el potencial terapèutic de diversos lligands del Sig-1R per promoure la supervivència de les MNs i el manteniment de la funció neuromuscular. Amb aquest propòsit, primer vam emprar el model in vitro de cultiu organotípic de medul·la espinal sotmès a una excitotoxicitat crònica i, a continuació, dos models murins, la lesió del nervi espinal i els ratolins transgènics SOD1G93A. Els nostres resultats in vitro van revelar que els lligands del Sig-1R provats (PRE-084, BD1063, SA4503, EST79232 i EST79376) augmentaven la supervivència de les MNs sotmeses a una excitotoxicitat crònica. D’altra banda, els estudis in vivo van demostrar que els efectes neuroprotectors observats diferien entre els diversos lligands del Sig-1R testats. En el model murí SOD1G93A, el tractament amb els diversos lligands del Sig-1R va ser capaç de preservar la funció i les unions neuromusculars de les extremitats posteriors, augmentar el nombre de MNs supervivents i modular la reactivitat glial a la medul·la espinal. Aquests lligands del Sig-1R també van ser capaços d’augmentar la supervivència de les MNs i modular la reactivitat glial després d’una lesió del nervi espinal. En conjunt, els resultats d’aquesta tesi aporten evidències clares que el Sig-1R és una diana interessant pel tractament de les MMN.Las enfermedades de las motoneuronas (EMN) son un grupo amplio de trastornos neurológicos esporádicos y hereditarios caracterizados por la degeneración de este tipo de neuronas, las motoneuronas (MNs), con afecciones muy debilitantes y grave con unas opciones terapéuticas limitadas. La esclerosis lateral amiotrófica (ELA), la EMN más frecuente en adultos, es una enfermedad neurodegenerativa mortal caracterizada por la degeneración de las MNs de la médula espinal y el cerebro. Actualmente, los tratamientos disponibles tienen efectos modestos sobre la supervivencia del paciente alargando la vida unos meses. Por tanto, existe una necesidad urgente de comprender los mecanismos moleculares implicados en la degeneración de las MNs para identificar nuevas dianas terapéuticas y desarrollar terapias eficaces que protejan y restauren la integridad neuronal. Recientemente, entre otras dianas para la neuroprotecion, el receptor Sigma-1 (Sig-1R) ha ganado interés. El objetivo de esta tesis era evaluar el potencial terapéutico de varios ligandos del Sig-1R para promover la supervivencia de las MNs y el mantenimiento de la función neuromuscular. Para ello, primero utilizamos el modelo in vitro de cultivo organotípico de médula espinal sometido a una excitotoxicidad crónica, y luego, dos modelos murinos, la lesión del nervio espinal y los ratones transgénicos SOD1G93A. Nuestros resultados in vitro revelaron que los ligandos del Sig-1R probados (PRE-084, BD1063, SA4503, EST79232 y EST79376) aumentaban la supervivencia de las MNs sometidas a una excitotoxicidad crónica. Por otro lado, los estudios in vivo mostraron que los efectos neuroprotectores observados diferían entre los diversos ligandos Sig-1R probados. En el ratón SOD1G93A, el tratamiento con varios ligandos Sig-1R fue eficaz para preservar la función y las uniones neuromusculares de las extremidades posteriores, aumentar el número de MNs supervivientes y modular la reactividad glial en la médula espinal. Estos ligandos del Sig-1R también fueron capaces de aumentar la supervivencia de las MNs y modular la reactividad glial después de una lesión del nervio espinal. En conjunto, los resultados de esta tesis proporcionan una clara evidencia de que el Sig-1R es una diana interesante para el tratamiento de las EMN.Motor neuron diseases (MND) include a wide type of sporadic and hereditary neurological disorders characterized by degeneration of motor neurons (MNs), and are highly debilitating and severe conditions for which only limited therapeutic options are available. Amyotrophic lateral sclerosis (ALS), the most frequent MND in adults, is a fatal neurodegenerative disease with degeneration of MNs in the spinal cord and the brain. Currently, available treatments have modest effects on patient survival. Thus, there is an urgent need to understand the molecular mechanisms involved in the MN degeneration to discover new therapeutic targets and develop effective therapies protecting and restoring neuronal integrity. Among the putative targets for neuroprotection, recently the Sigma-1 receptor (Sig-1R) has gained attention. The aim of the present thesis was to assess the therapeutic potential of several Sig-1R ligands for promoting MN survival and maintenance of neuromuscular function. For this purpose, we first used an in vitro model of spinal cord organotypic culture subjected to chronic excitotoxicity, and then, two murine models, the spinal nerve injury and the transgenic SOD1G93A mice. Our in vitro results revealed that the Sig-1R ligands tested (PRE-084, BD1063, SA4503, EST79232 and EST79376) increased MN survival under chronic excitotoxicity. On the other hand, in vivo studies showed that the neuroprotective effects observed differed between the Sig-1R ligands tested. In the SOD1G93A mouse treatment with several Sig-1R ligands was effective to preserve neuromuscular function and junctions of the hindlimbs, to increase the number of surviving MNs and to modulate glial reactivity in the spinal cord. These Sig-1R ligands were also able to increase MN survival and modulate glial reactivity after a spinal nerve injury. Altogether, the results of this thesis provide clear evidence that Sig-1R is an interesting target for the treatment of MND.Universitat Autònoma de Barcelona. Programa de Doctorat en Neurocièncie
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Sigma-1 Receptor is a Pharmacological Target to Promote Neuroprotection in the SOD1 G93A ALS Mice
Get PDFAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the death of motoneurons (MNs) with a poor prognosis. There is no available cure, thus, novel therapeutic targets are urgently needed. Sigma-1 receptor (Sig-1R) has been reported as a target to treat experimental models of degenerative diseases and, importantly, mutations in the Sig-1R gene cause several types of motoneuron disease (MND). In this study we compared the potential therapeutic effect of three Sig-1R ligands, the agonists PRE-084 and SA4503 and the antagonist BD1063, in the SOD1 G93A mouse model of ALS. Pharmacological administration was from 8 to 16 weeks of age, and the neuromuscular function and disease progression were evaluated using nerve conduction and rotarod tests. At the end of follow up (16 weeks), samples were harvested for histological and molecular analyses. The results showed that PRE-084, as well as BD1063 treatment was able to preserve neuromuscular function of the hindlimbs and increased the number of surviving MNs in the treated female SOD1 G93A mice. SA4503 tended to improve motor function and preserved neuromuscular junctions (NMJ), but did not improve MN survival. Western blot analyses revealed that the autophagic flux and the endoplasmic reticulum stress, two pathways implicated in the physiopathology of ALS, were not modified with Sig-1R treatments in SOD1 G93A mice. In conclusion, Sig-1R ligands are promising tools for ALS treatment, although more research is needed to ascertain their mechanisms of action
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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