Contents
Academic literature on the topic 'Sclérose latérale amyotrophique – Modèles mathématiques'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Sclérose latérale amyotrophique – Modèles mathématiques.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Sclérose latérale amyotrophique – Modèles mathématiques"
Le Verche, Virginia. "Nécroptose des motoneurones dans des modèles de sclérose latérale amyotrophique familiale ou sporadique." médecine/sciences 30, no. 8-9 (August 2014): 748–50. http://dx.doi.org/10.1051/medsci/20143008011.
Full textDupuis, L., A. Muller, V. Meininger, and J. P. Loeffler. "Mécanismes moléculaires de la sclérose latérale amyotrophique : apports récents de l’analyse de modèles animaux." Revue Neurologique 160, no. 1 (January 2004): 35–43. http://dx.doi.org/10.1016/s0035-3787(04)70845-0.
Full textBoumédiène, F., B. Marin, V. Bonneterre, W. Camu, P. Couratier, and P. M. Preux. "Modèles géographiques pour l’étude de l’incidence de la sclérose latérale amyotrophique (SLA) et de ses interactions spatiales avec les expositions environnementales collectives de quelques facteurs environnementaux d’intérêts étiologiques, Limousin, France." Revue d'Épidémiologie et de Santé Publique 59 (April 2011): S10—S11. http://dx.doi.org/10.1016/j.respe.2011.02.079.
Full textDissertations / Theses on the topic "Sclérose latérale amyotrophique – Modèles mathématiques"
Ortholand, Juliette. "Joint modelling of events and repeated observations : an application to the progression of Amyotrophic Lateral Sclerosis." Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS227.
Full textProgression heterogeneity in chronic diseases such as Amyotrophic Lateral Sclerosis (ALS) is a significant obstacle to developing effective treatments. Leveraging the growing wealth of large databases through modelling can help better understanding it. However, the data collected only offer access to partial trajectories, that need to be realigned to reconstruct a comprehensive disease progression. To address this challenge, data-driven progression models like the longitudinal Spatiotemporal model were developed. Its main interest is its ability to synchronise patients onto a common disease timeline (temporal aspect) thanks to a latent disease age, while also capturing the remaining variability through parameters that account for outcome ordering (spatial aspect). However, this model was primarily designed for longitudinal data, overlooking crucial outcomes in ALS such as time to death or initiation of life support, like Non-Invasive Ventilation (NIV). Conversely, existing joint models offer the advantage of simultaneously handling longitudinal and survival data. However, they do not realign trajectories, which compromises their temporal resolution. This thesis aimed to expand the Spatiotemporal model into a Joint Spatiotemporal model, enabling, for ALS research, the examination of survival data alongside longitudinal data. First, we applied the Spatiotemporal model to explore how the interaction between sex and onset site (spinal or bulbar) impacts the progression of ALS patients. We selected 1,438 patients from the PRO-ACT database. We demonstrated a significant influence of both sex and onset site on six longitudinal outcomes monitoring the functional and respiratory decline in addition to Body Mass Index. However, this study did not incorporate survival analysis, despite its paramount importance in ALS, due to limitations inherent to the Spatiotemporal model. To address this gap, we associated the Spatiotemporal model with a survival model that estimates a Weibull survival model from its latent disease age, creating a univariate Joint Temporal model. After model validation, we benchmarked our model with a state-of-the-art joint model on PRO-ACT data. Our model exhibited significantly superior performance in terms of absolute bias and mean cumulative AUC for right-censored events. This demonstrated the efficacy of our approach in the context of ALS compared to existing joint models. However, modelling several longitudinal outcomes requires a multivariate approach. Life support initiation that might be censored by death needs to be also considered. We thus extended the Joint Temporal model, into a multivariate Joint Spatiotemporal model with competing risks to analyse NIV initiation. This involved coupling the multivariate Spatiotemporal model with a cause-specific Weibull survival model from the latent disease age. We incorporated spatial parameters with a Cox proportional effect on the hazard. After validation, we benchmarked our model with a state-of-the-art joint model on PRO-ACT data and analysed sex and onset site interaction in complement to the first study. The Joint Spatiotemporal model achieved similar performance to the state-of-the-art model while capturing an underlying shared latent process, the latent disease age, whereas the state-of-the-art models the impact of longitudinal outcomes on survival. To enhance the reproducibility and facilitate the reuse of these models, the proposed models were implemented in the open-source software Leaspy. In conclusion, this thesis introduces the first data-driven progression model combining longitudinal and survival modelling. We demonstrated its relevance to understand the occurrence of critical events in ALS. This work paves the way for further extension to analyse recurrent events, among other potential applications in causal inference
Langou, Karine. "Développement de nouveaux modèles expérimentaux de la Sclérose Latérale Amyotrophique." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX22033.
Full textALS is a neurodegenerative disease characterized by a selective loss of motor neurons. A mutation in VAPB protein has been associated with ALS. VAPB, an endoplamic reticulum (ER) resident protein is proposed to play a role in protein transport and in the unfolded protein response. To manipulate VAPB (hVAPBwt and hVAPBp56s) expression in motor neurons in vitro, I used the viral gene transfer technology. hVAPBp56s induces selective motor neuron death which involved an ER-related pathway dependent on calcium signals. Studies on Cos-7 cells showed that hVAPBwt and hVAPBp56s impair the proteasome activity through the activation of ER stress and the sequestration of the 20S subnit. Moreover, we developed transgenic mice overxpressing hVAPBp56s which do not display any motor disorder
Abou, Ezzi Samer. "Chromogranines et pathogenèse de la sclérose latérale amyotrophique." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/27148/27148.pdf.
Full textPicchiarelli, Gina. "Rôle du muscle squelettique dans la Sclérose Latérale Amyotrophique : apport de modèles transgéniques conditionnels." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ054.
Full textAmyotrophic lateral sclerosis is a neurodegenerative whose first symptoms generally appear around age 60. It is characterized by progressive motor neuron degeneration, paralysis and leading to death due to respiratory failure in a few years. Currently, there is no cure so the understanding of ALS physiopathology is necessary. Although many alterations in the muscle have been highlighted, its contribution in ALS remains to be defined. We showed that FUS is enriched in subsynaptic nuclei and this enrichment depended on innervation. Besides, FUS binds directly acetylcholine receptors (AchR) promoter and is required for Ermdependent induction of AChR expression. Conversely, mutant FUS is enriched on extra-synaptic nuclei and induce muscle intrinsic toxicity responsible for neuromuscular junction (NMJ) alteration. Beyond NMJ, FUS is required for muscle mitochondrial function and muscle differentiation through PRMT1-dependent MEF2A activation. Thus, FUS muscular toxicity plays a key role in the ALS physiopathology
Mesci, Pinar. "L’implication du système xc- et du glutamate microglial dans les modèles murins de la sclérose latérale amyotrophique (SLA)." Paris 6, 2013. http://www.theses.fr/2013PA066286.
Full textAmyotrophic lateral sclerosis (ALS) is the most common adult onset motor neuron disease leading to paralysis and death of patients. Mutations in SOD1 are responsible for motor neuron degeneration through a non-cell autonomous mechanism. Microglial cells, the macrophages of the central nervous system, participate in the progression of the disease. Since ALS is mainly sporadic, targeting the symptomatic phase during which microglial cells are actively involved is relevant to ALS. Since microglial neurotoxic factors are still largely unidentified in ALS and excitotoxicity is one pathway suggested to cause motor neuron death, our hypothesis was to assess if glutamate released by microglia through system xc- (a cystine/glutamate antiporter with the specific subunit xCT) could participate to motor neuron death in ALS. We now show that primary microglial cells expressed xCT and to a higher level upon activation, that xCT transcripts were enriched in microglia compared to the whole spinal cord and absent in motor neurons. In addition, xCT mRNA levels were increased in mutant SOD1 mouse spinal cords during disease progression. Deleting xCT in mutant SOD1 mice accelerated the onset of the disease but increased the duration of the symptomatic phase. Microglial system xc- was responsible for release of glutamate by microglial cells and deleting xCT increased the neurotrophic profile of microglial cells. These results show that system xc- could be a good target to slow ALS disease progression
Gowing, Geneviève. "Le rôle de l'inflammation et des microglies dans la sclérose latérale amyotrophique." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26199/26199.pdf.
Full textHalter, Benoît. "Dérégulation du transcriptôme musculaire et analyse des mécanismes physio-pathologiques lors de la sclérose latérale amyotrophique." Strasbourg, 2009. http://www.theses.fr/2009STRA6115.
Full textAmyotrophic Lateral Sclerosis (ALS) is a lethal neurodegenerative disease characterized by motorneuron death and muscular atrophy. Most cases are sporadic, however familial forms also exist, as a result of a dominant mutation in the superoxide dismutase 1 (SOD1) gene, which enabled the generation of animal models developing an experimental form of ALS. Several teams, including our lab, involve the muscle in the pathological process. We thus undertook a global study to investigate muscular transcriptome modifications during ALS pathology. This study generated a transcriptional "signature" of the disease, which could be used as basis to develop diagnostic tests, and revealed genes of interest in this pathology. First, we studied Rad because of its precocity and the intensity of its regulation in SOD1 mice, compared to wild type animals. We described the mechanisms regulating rad expression as well as the pathological phenomenon responsible for its induction. (Confirmed in human patients). Furhthermore, ALS is associated with hypermetabolism which, once compensated, increases animal’s survival. To better understand this hypermetabolism, we studied the implication of a second gene: the stearoyl-coenzyme-A desaturase 1 (SCD1) a key enzyme in mono unsatured fatty acids biosynthesis. SCD1 mRNA is specifically repressed in ALS muscle and its invalidation is known to trigger hypermetabolism in wild type animals. We thus hope to have identified one of the genes responsible for ALS-associated hypermetabolism. My work has therefore provided a muscular transcriptom "signature" in ALS and allowed us to identify target genes crucial for the fundamental understanding of the pathology
Patel, Priyanka. "Development of new therapeutic approaches in mouse models of Amyotrophic Lateral Sclerosis." Doctoral thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/25851.
Full textAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. Although numerous pathological mechanisms have been elucidated, ALS still remains a medical mystery in the absence of any effective therapy. Riluzole is the only therapeutic drug approved for ALS with regard to prolonging survival. Here, we have developed two strategies for treatment of ALS, first targeting the misfolded SOD1 (chapter 2) and other targeting neuroinflammation (chapter 3). In chapter 2, we aimed to reduce the level of misfolded SOD1 species in the nervous system. We tested a novel therapeutic approach based on adeno-associated virus (AAV)-mediated tonic expression of a DNA construct encoding a secretable single chain fragment variable (scFv) antibody composed of the variable heavy and light chain regions of a monoclonal antibody (D3H5) binding specifically to misfolded SOD1. A single intrathecal injection of the adeno-associated virus encoding the single chain antibody in SOD1G93A mice delayed disease onset and extended the life span by up to 28%, in direct correlation with scFv titers in the spinal cord. Our second treatment strategy which is aimed to target neuroinflammation is based on previous reports from our lab where it has been shown that Withaferin A (WA), an inhibitor of NF-κB activity was efficient in reducing disease phenotype in TDP-43 transgenic mouse model of ALS. We tested WA in mice from two transgenic lines expressing different ALS-linked SOD1 mutations, SOD1G93A and SOD1G37R. The beneficial effects of WA in SOD1G93A mice model was accompanied by alleviation of neuroinflammation, decrease in level of misfolded SOD1 species in spinal cord, a reduction in loss of motor neurons, resulting in delayed disease progression and mortality. Based on these evidences, AAV encoding a secretable scFv against misfolded SOD1 and WA should be considered as a potential treatment for ALS.
Pambo-Pambo, Arnaud Brice. "Etude du développement postnatal des motoneurones lombaires de deux souches de souris transgéniques, modèles de la sclérose latérale amyotrophique." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX20716.
Full textThe SOD1 murine models of Amyotrophic Lateral Sclerosis (ALS) allowed major progress in the understanding of mechanisms which could lead to a selective loss of motoneurons (Mns), but these models display differences in the severity and time course of the disease. Changes in intrinsic properties of motoneurons may induce changes in excitability and intracellular calcium homeostasis leading to motoneuron death.Therefore, we studied electrophysiological properties of lumbar Mns from SOD1G85R and SOD1G93A mice, low expressor lines, during the first two postnatal weeks in order to identify possible early presymptomatic abnormalities. Our studies were carried out on two in vitro preparations: the whole isolated spinal cord and acute spinal cord slices. Mutant Mns display, in the two preparations, a modified action potential characterized by an increased duration due to a decrease of the maximal speeds of depolarisation and repolarisation and a reduction of the spike amplitude. These alterations appeared between P2-P5 in SOD1G85R Mns and between P6-P10 in SOD1G93A Mns and suggest a decrease of the density of sodium and potassium channels related to action potential. We also showed on spinal cord slices between P6-P10 that the gain of frequency decreases for SOD1G85R Mns and increases for SOD1G93A Mns without any change in the density of persistent inward sodium or calcium currents in these different mutant Mns. We observed also that the resting membrane potential of SOD1G93A Mns on spinal cord slices is decreased. The membrane properties of SOD1G85R Mns between P6-P10 were less susceptible to changes in presence of an extracellular calcium overload. Differential effects of this extracellular calcium overload on membrane properties of WT and SOD1G85R Mns could be due to different alterations of the potential dependence of voltage-gated channels and/or to the modulation of some types of channels sensitive to extracellular calcium. An over-branching of dendritic arborization, similar to that previously described in SOD1G85R Mns, was observed in SOD1G93A at P8-P9 with the above-mentioned action potential alterations and a weak rheobasic current. These morphogical and electrical changes could indicate together alterations of kinetics and/or density of channels on different sites on these Mns. In conclusion, our work shows on one hand that SOD1G85R and SOD1G93A mutations induce similar alterations of lumbar Mns properties but time-shifted in these two murine models and on the other hand that some alterations seem to be specific to a given SOD1 mutation
Leparc-Goffart, Isabelle. "Modèles de persistance des entérovirus : myocardiopathie expérimentale murine à coxsackievirus B3 et syndrome post-poliomyélitique chez l'homme." Lyon 1, 1995. http://www.theses.fr/1995LYO1T294.
Full text