Variation des propriétés électrophysiologiques des cellules pyramidales dans animodel de dysplasie corticale

Rational: Cortical dysplasia has been associated with intractable epilepsy by many clinical studies. Animal model of cortical dysplasia using cortical freeze lesion in early development stage mimic the microgyra described in human. Methods: Cortical freeze lesion was performed in anesthetised new born rat at postnatal day 1. Whole cell current clamp recordings were used to investigate the changes in electrophysiological properties of CA1 pyramidal cells in this model. Results: The membrane potential and input resistance of CA1 pyramidal cells were not affected in this model. However the action potential threshold was lowered in lesion group and accompanied by an increase in the firing frequency in response to depolarising currents. In addition, the amplitude of spike afterhyperpolarisations was significantly decreased in lesion group. Conclusion: The increase excitability of CA1 pyramidal cells in cortical freeze lesion may increase the likelihood to develop epilepsy at adulthood.Rationnel: La dysplasie corticale a été associée à l’épilepsie réfractaire par de nombreuses études cliniques. Le modèle animal de la dysplasie corticale utilisant une lésion corticale au froid durant le premier jour postnatal reproduit la microgyrie décrite chez l’homme. Méthodes: La lésion corticale au froid a été réalisée sur des rats nouveau-nés anesthésiés. Les enregistrements électrophysiologiques ont été réalisés pour étudier les changements dans les propriétés électriques des cellules pyramidales de la région CA1 de l’hippocampe dans ce modèle. Résultats: Le potentiel de membrane et la résistance membranaire d’entrée des cellules pyramidales CA1 n’ont pas été affectés dans ce modèle. Cependant, une baisse du seuil du potentiel d’action accompagnée d’une augmentation de la fréquence de décharge en réponse à des courants dépolarisants ont été observés dans le groupe lésion. En outre, l’amplitude des post-hyperpolarisations était significativement diminuée dans le groupe lésion. Conclusion: L’augmentation de l’excitabilité des cellules pyramidales CA1 après lésion corticale peut contribuer à l’augmentation du risque de développer l’épilepsie à l’âge adulte

Toward SLM Cost model estimation: stainless steels case study

Additive manufacturing is a capable process to produce three dimensional components from raw material and 3D design data. This layer-by-layer operating process has many advantages including high geometrical freedom to produce complex parts with reduced cost and applied especially in the aerospace, medical and automotive industry. One of the metal AM processes is Selective Laser Melting this technology is an effective manufacturing technique to build metallic and functional parts. The aim of this study is to perform an economic assessment of Selective Laser Melting by developing a cost estimation model to estimate the process cost along the process life cycle cost. The cost of manufacturing is the key point for decision making to compare the Selective Laser Melting technology with different manufacturing technologies. The cost estimation is profitable also for engineers at the preliminary design. Production costs are studied to find out parameters influencing the Selective Laser Melting process such as machine cost, material, and post processing and how is the process cost could be optimized. A case study on Selective Laser Melting of stainless steels is presented to illustrate the cost model. This work presents a more realistic cost model of Selective Laser Melting based on the activity approach and including all steps of manufacturing with SLM such as part design and post processing such as heat treatment. This research enables us to understand the entire value network of Selective Laser Melting. It has been found that, the machine cost was by far the largest factor in Selective Laser Melting, followed by the post processing cost

Toward SLM Cost model estimation: stainless steels case study

Additive manufacturing is a capable process to produce three dimensional components from raw material and 3D design data. This layer-by-layer operating process has many advantages including high geometrical freedom to produce complex parts with reduced cost and applied especially in the aerospace, medical and automotive industry. One of the metal AM processes is Selective Laser Melting this technology is an effective manufacturing technique to build metallic and functional parts. The aim of this study is to perform an economic assessment of Selective Laser Melting by developing a cost estimation model to estimate the process cost along the process life cycle cost. The cost of manufacturing is the key point for decision making to compare the Selective Laser Melting technology with different manufacturing technologies. The cost estimation is profitable also for engineers at the preliminary design. Production costs are studied to find out parameters influencing the Selective Laser Melting process such as machine cost, material, and post processing and how is the process cost could be optimized. A case study on Selective Laser Melting of stainless steels is presented to illustrate the cost model. This work presents a more realistic cost model of Selective Laser Melting based on the activity approach and including all steps of manufacturing with SLM such as part design and post processing such as heat treatment. This research enables us to understand the entire value network of Selective Laser Melting. It has been found that, the machine cost was by far the largest factor in Selective Laser Melting, followed by the post processing cost

Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures.

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients\u27 quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even been shown to exacerbate injury in a rat model of temporal lobe epilepsy. We hypothesized that ACTH exerted positive effects on cognitive outcomes through beneficial changes to gene expression and proposed that administration of ACTH at seizure induction would return gene-expression in the brain towards the normal pattern of expression in the Control animals whereas Dex would not. Twenty-six Sprague-Dawley rats were randomized into vehicle- Control, and ACTH-, Dex-, and vehicle- ELS. Rat pups were subjected to 60 flurothyl seizures from P5 to P14. After seizure induction, brains were removed and the hippocampus and PFC were dissected, RNA was extracted and sequenced, and differential expression analysis was performed using generalized estimating equations. Differential expression analysis showed that ACTH pushes gene expression in the brain back to a more normal state of expression through enrichment of pathways involved in supporting homeostatic balance and down-regulating pathways that might contribute to excitotoxic cell-damage post-ELS

Risk management culture: reality & stakes, case of enterprises of Tangier - Tetouan - Al Hoceima region in Morocco

The enterprise takes risks on a daily basis, which can be operational, organizational or management risks. The latter remain a decision support tool and a crucial means to ensure the enterprise’s sustainability. In this framework, this article we set out to address this issue by conducting an empirical survey about the reality of risk management within enterprises in morocco.The purpose is to characterize the main risks faced by the surveyed enterprises and to have an overview about the key factors in risk management. The findings reveal that the culture of risk management differs from one enterprise to another. Moreover, the results assert that despite the difference in business activities, the enterprises assess their risk using conventional risk assessment methods

Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation

<p>Abstract</p> <p>Background</p> <p>Agonist stimulation of airway smooth muscle (ASM) results in IP₃mediated Ca²⁺release from the sarcoplasmic reticulum followed by the activation of store operated and receptor operated non-selective cation channels. Activation of these non-selective channels also results in a Na⁺influx. This localised increase in Na⁺levels can potentially switch the Na⁺/Ca²⁺exchanger into reverse mode and so result in a further influx of Ca²⁺. The aim of this study was to characterise the expression and physiological function of the Na⁺/Ca²⁺exchanger in cultured human bronchial smooth muscle cells and determine its contribution to agonist induced Ca²⁺influx into these cells.</p> <p>Methods</p> <p>The expression profile of NCX (which encodes the Na⁺/Ca²⁺exchanger) homologues in cultured human bronchial smooth muscle cells was determined by reverse transcriptase PCR. The functional activity of reverse mode NCX was investigated using a combination of whole cell patch clamp, intracellular Ca²⁺measurements and porcine airway contractile analyses. KB-R7943 (an antagonist for reverse mode NCX) and target specific siRNA were utilised as tools to inhibit NCX function.</p> <p>Results</p> <p>NCX1 protein was detected in cultured human bronchial smooth muscle cells (HBSMC) cells and NCX1.3 was the only mRNA transcript variant detected. A combination of intracellular Na⁺loading and addition of extracellular Ca²⁺induced an outwardly rectifying current which was augmented following stimulation with histamine. This outwardly rectifying current was inhibited by 10 μM KB-R7943 (an antagonist of reverse mode NCX1) and was reduced in cells incubated with siRNA against NCX1. Interestingly, this outwardly rectifying current was also inhibited following knockdown of STIM1, suggesting for the first time a link between store operated cation entry and NCX1 activation. In addition, 10 μM KB-R7943 inhibited agonist induced changes in cytosolic Ca²⁺and induced relaxation of porcine peripheral airways.</p> <p>Conclusions</p> <p>Taken together, these data demonstrate a potentially important role for NCX1 in control of Ca²⁺homeostasis and link store depletion via STIM1 directly with NCX activation.</p

Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis

Background: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. Methodology/Principal Findings: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. Conclusions/Significance: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl

Age-Related Changes of Myelin Basic Protein in Mouse and Human Auditory Nerve

Age-related hearing loss (presbyacusis) is the most common type of hearing impairment. One of the most consistent pathological changes seen in presbyacusis is the loss of spiral ganglion neurons (SGNs). Defining the cellular and molecular basis of SGN degeneration in the human inner ear is critical to gaining a better understanding of the pathophysiology of presbyacusis. However, information on age-related cellular and molecular alterations in the human spiral ganglion remains scant, owing to the very limited availably of human specimens suitable for high resolution morphological and molecular analysis. This study aimed at defining age-related alterations in the auditory nerve in human temporal bones and determining if immunostaining for myelin basic protein (MBP) can be used as an alternative approach to electron microscopy for evaluating myelin degeneration. For comparative purposes, we evaluated ultrastructural alternations and changes in MBP immunostaining in aging CBA/CaJ mice. We then examined 13 temporal bones from 10 human donors, including 4 adults aged 38–46 years (middle-aged group) and 6 adults aged 63–91 years (older group). Similar to the mouse, intense immunostaining of MBP was present throughout the auditory nerve of the middle-aged human donors. Significant declines in MBP immunoreactivity and losses of MBP+ auditory nerve fibers were observed in the spiral ganglia of both the older human and aged mouse ears. This study demonstrates that immunostaining for MBP in combination with confocal microscopy provides a sensitive, reliable, and efficient method for assessing alterations of myelin sheaths in the auditory nerve. The results also suggest that myelin degeneration may play a critical role in the SGN loss and the subsequent decline of the auditory nerve function in presbyacusis