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on Neuroeconomics |
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Issue of 2011‒02‒05
three papers chosen by |
| By: | Rajakulendran, S. |
| Abstract: | Mutations in the shaker potassium channel (KV1.1) gene KCNA1 are associated with episodic ataxia type 1 (EA1) while mutations in the CACNA1A gene which encodes the CaV2.1 calcium channel underlie episodic ataxia type 2 (EA2). Both disorders exhibit dominant inheritance and are characterised clinically by paroxysmal attacks of cerebellar dysfunction. This thesis explores the relationship between six new mutations in KCNA1, EA1 phenotype and functional consequences of expressed mutations. Expression of all six mutations demonstrated a loss of function. There was an imperfect correlation between phenotypic severity of EA1 and in vitro electrophysiology with respect to mutations. Supporting this indirect relationship, this thesis reports that non-genetic factors influence the phenotypic outcome of EA1 in monozygotic twins. In recognition of the importance of studying mutations in physiologically relevant conditions, this thesis describes the use of a lentivirus as a tool for studying the effects of KCNA1 mutations in neurons. A number of individuals with clinical EA2 do not harbour point mutations in CACNA1A. A screen for rearrangements in eighteen such individuals identified deletions of at least one exon of CACNA1A in three patients with EA2 suggesting that such large deletions are an important cause of EA2. This thesis tested the hypothesis that genetic variation in CACNA1A conferring a loss of CaV2.1 function is associated with the syndrome of episodic ataxia with epilepsy. CACNA1A was sequenced in 17 individuals with a clinical phenotype of EA accompanied by epilepsy and/or epileptiform EEGs. The functional impact of newly identified missense mutations and all non-synonymous coding variants (nCVs) in the 17 individuals was determined using voltage clamp experiments. Twelve of the 17 patients had genetic variants which reduced CaV2.1 function. These findings suggest that variations in CACNA1A which result in varying degrees of loss of channel function are likely to predispose individuals to episodic ataxia with epilepsy. |
| Date: | 2010–11–28 |
| URL: | http://d.repec.org/n?u=RePEc:ner:ucllon:http://discovery.ucl.ac.uk/644702/&r=neu |
| By: | Thierry Chauveau (CES - Centre d'économie de la Sorbonne - CNRS : UMR8174 - Université Panthéon-Sorbonne - Paris I); Nicolas Nalpas (Toulouse Business School - ESC Toulouse) |
| Abstract: | In this paper, a fully choice-based theory of disappointment is developed. It encompasses, as particular cases, EU theory, Gul's theory of disappointment (1991) and the models of Loomes and Sugden (1986). According to the new theory, the risk premium of a random prospect is the sum of two premiums : a concavity premium that is nothing but the usual Arrow-Pratt premium and a second premium that may be identified to expected disappointment. The corresponding representing functional belongs to the class of lottery-dependent utility models (Becker and Sarin 1987) since disappointment is the deficit between the utility of the realized outcome and its expected value. However, unlike the lottery-dependent approach, the theory is choice-based and its axioms are experimentally testable. |
| Keywords: | Axiomatisation, aversion pour la déception, revenu aléatoire, prime de risque, utilité espérée. |
| Date: | 2010–12 |
| URL: | http://d.repec.org/n?u=RePEc:hal:cesptp:halshs-00560543&r=neu |
| By: | Menghi, F. |
| Abstract: | Medulloblastoma is a malignant embryonal tumour of the cerebellum which most commonly affects children. A subset of tumours is thought to arise from cerebellar granule cell precursors (GCPs) that fail to undergo normal neuronal development, following the hyper-activation of the Sonic hedgehog (Shh) signalling pathway. To identify candidate genes that might be important for medulloblastoma pathogenesis, I investigated patterns of gene expression and alternative splicing in 14 paediatric medulloblastoma and five normal cerebellar samples using Affymetrix Human Exon arrays. Statistical analysis of the gene expression data identified a group of medulloblastomas with a molecular signature of Shh pathway activation. These tumours showed higher expression levels of genes involved in spindle formation, cytokines, and cell cycle regulation. Further studies using an in vitro mouse GCP cell culture model, in which Shh is necessary for the maintenance of the progenitor state, showed that a selection of candidate genes was also over-expressed when GCPs were cultured in the presence of Shh, as compared to control cells, as well as in human medulloblastoma cell lines. Ongoing and future in vitro experiments will investigate the potential role of candidate genes in sustaining the growth of precursor and tumour cells. Exon-level analysis of gene expression showed that abnormal expression of different transcript variants is likely to occur in medulloblastoma. I selected several examples of differential exon usage and validated these using an independent set of normal and tumour specimens. Tumour-associated splicing alterations were highly consistent, enabling clear separation of normal and cancer samples and in some cases of different medulloblastoma molecular subgroups. Interestingly, Shh-treated GCPs recapitulated the splicing patterns observed in the tumour samples for six out of the eight genes analysed, suggesting that the preferential expression of specific transcript forms is regulated during normal cerebellar development. The possible relationship between inappropriate splicing and medulloblastoma pathogenesis will be the subject of future investigation. |
| Date: | 2010–11–28 |
| URL: | http://d.repec.org/n?u=RePEc:ner:ucllon:http://discovery.ucl.ac.uk/642570/&r=neu |