436 research outputs found
c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.
The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue
PharOS, a multicore OS ready for safety-related automotive systems: results and future prospects
International audienceAutomotive electrical/electronic architectures need to perform more and more functions that are mapped onto many different electronic control units (ECU) because of their different safety levels or different application domains (body, powertrain, multimedia, etc.). Freedom of interference is required to comply with the upcoming ISO 26262 standard for mixing different ASIL levels on the same ECU and is also required to cope with the safe integration of software from different suppliers. PharOS provides dedicated software partitioning mechanisms as well as controlled and efficient resource sharing by construction, from the design to the implementation stages. The main features of PharOS, contributing to this property, are presented in this paper as well as the results on its application an industry-driven case study and associated future prospects
Cerebellar Contribution to Preparatory Activity in Motor Neocortex
In motor neocortex, preparatory activity predictive of specific movements is maintained by a positive feedback loop with the thalamus. Motor thalamus receives excitatory input from the cerebellum, which learns to generate predictive signals for motor control. The contribution of this pathway to neocortical preparatory signals remains poorly understood. Here, we show that, in a virtual reality conditioning task, cerebellar output neurons in the dentate nucleus exhibit preparatory activity similar to that in anterolateral motor cortex prior to reward acquisition. Silencing activity in dentate nucleus by photoactivating inhibitory Purkinje cells in the cerebellar cortex caused robust, short-latency suppression of preparatory activity in anterolateral motor cortex. Our results suggest that preparatory activity is controlled by a learned decrease of Purkinje cell firing in advance of reward under supervision of climbing fiber inputs signaling reward delivery. Thus, cerebellar computations exert a powerful influence on preparatory activity in motor neocortex
Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients
Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy
Semiology, clustering, periodicity and natural history of seizures in an experimental occipital cortical epilepsy model
Focal neocortical epilepsy is a common form of epilepsy and there is a need to develop animal models that allow the evaluation of novel therapeutic strategies to treat this type of epilepsy. Tetanus toxin (TeNT) injection into the rat visual cortex induces focal neocortical epilepsy without preceding status epilepticus. The latency to first seizure ranged from 3 to 7 days. Seizure duration was bimodal, with both short (approximately 30 s) and long-lasting (>100 s) seizures occurring in the same animals. Seizures were accompanied by non-motor features such as behavioural arrest, or motor seizures with or without evolution to generalized tonic-clonic seizures. Seizures were more common during the sleep phase of a light-dark cycle. Seizure occurrence was not random, and tended to cluster with significantly higher probability of recurrence within 24 h of a previous seizure. Across animals, the number of seizures in the first week could be used to predict the number of seizures in the following 3 weeks. The TeNT model of occipital cortical epilepsy is a model of acquired focal neocortical epilepsy that is well-suited for preclinical evaluation of novel anti-epileptic strategies. We provide here a detailed analysis of the epilepsy phenotypes, seizure activity, electrographic features and the semiology. In addition, we provide a predictive framework that can be used to reduce variation and consequently animal use in preclinical studies of potential treatments
Hand-rolled cigarette smoking patterns compared with factory-made cigarette smoking in New Zealand men
<p>Abstract</p> <p>Background</p> <p>Roll-your-own (RYO) cigarettes have increased in popularity, yet their comparative potential toxicity is uncertain. This study compares smoking of RYO and factory-made (FM) cigarettes on smoking pattern and immediate potential toxicity.</p> <p>Methods</p> <p>At a research clinic, 26 RYO and 22 FM volunteer male cigarette smokers, (addicted and overnight-tobacco-abstinent) each smoked 4 filter cigarettes, one half-hourly over 2 hours, either RYO or FM according to usual habit, using the CReSSMicro flowmeter. First cigarette smoked was their own brand. Subsequent cigarettes, all Holiday regular brand, were RYOs (0.5 g tobacco with filter), or FM with filter. Cravings on 100 mm visual analogue scale, and exhaled carbon monoxide (CO) were measured before and after each cigarette smoked.</p> <p>Results</p> <p>Smokers reported similar daily cigarette consumption (RYO 19.0, FM 17.4, p = 0.45), and similar time after waking to first cigarette. (RYO 6.1 minutes, FM 8.6 minutes, p = 0.113). First cigarette's RYO tobacco (0.45 g) weighed less than for FM (0.7 g, p < 0.001); less tobacco was burnt (0.36 g, FM 0.55 g, p < 0.001) but smoking patterns were no different. RYO smokers smoked subsequent cigarettes more intensively; inhaled 28% more smoke per cigarette (RYO 952 mL, FM 743 mL, p = 0.025); took 25% more puffs (RYO 16.9, FM 13.6, p = 0.035); puffed longer (RYO 28 seconds, FM 22 seconds, p = 0.012), taking similar puffs (RYO 57 mL, FM 59 mL). Over four cigarettes, RYOs boosted alveolar CO (RYO 13.8 ppm, FM 13.8 ppm), and reduced cravings (RYO 53%, FM 52%) no differently from FM cigarettes.</p> <p>Conclusion</p> <p>In these smokers, RYO smoking was associated with increased smoke exposure per cigarette, and similar CO breath levels, and even with filters is apparently no less and possibly more dangerous than FM smoking. Specific package warnings should warn of RYO smoking's true risk. RYOs are currently taxed much less than FM cigarettes in most countries; similar harm merits similar excise per cigarette.</p
L'estime de soi globale et physique à l'adolescence
International audienceObjective. From a data collection conducted among junior high-school students, we propose to assess global and physical self-esteem. Indeed, profound physical changes, psychological and social affect this phase of development of the person and the object of this article is to clarify what are the potential impacts of these changes on self-esteem as a function of age and gender. Methods. 579 junior high-school students of the Midi Pyrenees region, aged 11 to 17 years (M = 13.34, SD = 1.20) have informed the Rosenberg self-esteem scale (1965) and the physical self-inventory (Ninot, Delignières and Fortes, 2000). Results. The reliability of both tools is confirmed from our study sample. The results allow to update significant differences in global and physical self-esteem according to the age and gender of the adolescents. Conclusion. The discussion focuses on the interpretation of gender differences in the assessment of global self-esteem and physical interpretation of the differences in the development of the person.Objectif de l'étude : À partir d'un recueil de données réalisé auprès d'élèves de collège, nous proposons d'évaluer l'estime de soi dans les domaines global et physique. En effet, de profondes modifications physiques, psychologiques et sociales affectent cette phase de développement de la personne et l'objet de cet article est de préciser quelles sont les répercussions possibles de ces transformations sur l'estime de soi en fonction de l'âge et du genre. Sujets : 579 collégien(ne)s de la région Midi Pyrénées, âgés de 11 à 17 ans (M = 13,34 ; ET = 1,20) ont renseigné l'échelle unidimensionnelle de Rosenberg (1965) et l'Inventaire de Soi Physique de Ninot, Delignières et Fortes (2000). Résultats. La fiabilité des deux outils utilisés est confirmée auprès de notre échantillon d'étude. Les résultats permettent de mettre à jour des différences significatives d'estime de soi globale et physique en fonction de l'âge et du genre des adolescent(e)s. Conclusion. La discussion s'oriente sur l'interprétation des différences de genre dans l'évaluation de l'estime de soi globale et physique et sur l'interprétation de différences au cours du développement de la personne
Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinérAIR-Sclérodermie study
Objectives. This longitudinal study investigated survival, risk factors and causes of death in the multicentre ItinérAIR-Sclérodermie cohort of patients with SSc without severe pulmonary fibrosis or severe left heart disease at baseline
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