Candidate genes for temporal lobe epilepsy: a replication study

The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in temporal lobe epilepsy (TLE): interleukin 1β (IL-1β), interleukin 1β (IL-1α), interleukin 1RA (IL-1RA), apolipoprotein E (ApoE) and prodynorphin (PDYN). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated TLE patients and matched controls. We were thus able to confirm the role of ApoE, IL-1α and IL-1RA genes in TLE disease, but failed to confirm the involvement of IL-1β and PDYN. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical powe

BRD2 and TAP-1 genes and juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is a genetically determined common subtype of idiopathic generalized epilepsy. Linkage of JME to the chromosomal region 6p21.3 has been reported. An association has been previously observed between JME and the positional candidate, 6p21.3 linked, BRD2. Another candidate in this region is the TAP-1 gene encoding the Transporter Associated with Antigen Processing. The aim of the present study is to determine whether these two genes modulate the vulnerability to JME. While no difference was observed in the allele and genotype frequencies of BRD2 between JME and controls, an association was found between a TAP-1 haplotype and JME, suggesting that this gene may be another 6p21.3 linked vulnerability factor to JM

Collecting Saliva by Mail for Genetic and Cotinine Analyses in Participants Recruited through the Internet

The authors assessed whether collection by mail of saliva and buccal cells for genetic analysis was feasible in participants recruited through the Internet. In 2003, 14,773 visitors of a smoking cessation website were invited by e-mail to take part in the study. Salivettes (plastic vials containing a cotton roll) were mailed to participants, for collection of saliva and buccal cells. Because of limited resources, the authors stopped recruitment when 392 participants (3% of 14,733) were registered. They received 315 saliva samples back (80% of 392). Salivary cotinine was analyzed in 145 daily smokers. Cotinine concentration could be assessed in 141 samples (97%) (range 0.7-899ng/ml, median 260ng/ml). DNA extraction was achieved in all the 285 samples in which it was attempted. Quality of DNA was assessed by optical density measurements and by polymerase chain reaction amplification of a gene coding for the α-4 nicotinic receptor, with the detection of a known polymorphism. Successful results were obtained in 235 samples (82% of 285). Thus collecting saliva by mail for cotinine and DNA analysis in participants recruited through the internet produced samples of good quality at a reasonable cost. This approach should be valuable for genetic epidemiology and pharmacogenetic researc

Study, in inter-didactics of mathematics and physics, about acquisition of Ohm's law in high school : space of reality

La question de déterminer sous quelles conditions des concepts élaborés dans le champ de la didactique d'une discipline donnée sont transposables à la didactique d'une autre discipline est régulièrement posée par de nombreux chercheurs. Pour notre part, nous nous sommes intéressés aux relations entre les mathématiques et la physique, en prenant l'exemple de la loi d'Ohm, première loi physique écrite et représentée sous forme mathématique au collège et au lycée en France. Pour rendre compte de nos observations, nous avons été amenés à définir un modèle théorique s'appuyant sur les notions de cadre et de registre développées de manière spécifique en didactique des mathématiques, en leur adjoignant pour la didactique de la physique une notion nouvelle, celle d'espace de réalité

Genetic association of the Phosphoinositide-3 kinase in schizophrenia and bipolar disorder and interaction with a BDNF gene polymorphism

Phosphoinositide-3-kinase, class III (PIK3C3) is a member of the phosphoinosite-3-kinases family, involved in cell signaling, membrane trafficking, and neurodevelopment. Previous studies have indeed shown an association between PIK3C3 gene variants and both bipolar disorder (BD) and schizophrenia (SZ). Brain-derived neurotrophic factor (BDNF) is a neurodevelopmental factor, which can regulate the PI3K signaling pathway. Associations have been reported between BDNF gene polymorphisms and affective and psychotic disorders. The aim of the present study was to replicate an association between PIK3C3 and BDNF gene variants in SZ and BD and a putative epistasis between the two genes. Patients meeting the DSM-IV criteria of BD and SZ were included in this study (98 BD and 79 SZ) as well as 158 healthy controls. Blood DNA was extracted and genotyping was performed either by the polymerase chain reaction (PCR) technique followed by enzymatic digestion or by the high-resolution melt (HRM) method. Genotype and haplotype association was assessed with the UNPHASED statistical program.The results showed one nominal association with BD (P < 0.02) and two risk haplotypes in both SZ (P < 0.001) and BP (P < 0.0005), which survived multiple testing correction. A modest interaction between a BDNF variant and PI3KC3 polymorphism was observed (P < 0.04).These preliminary results confirm the genetic association of PI3K gene variants with both SZ and BD, and support the hypothesis that SZ and BD share a genetic background

Notions de registre et de cadre de rationalité en inter-didactique des mathématiques et de la physique

La question de déterminer sous quelles conditions des concepts élaborés dans le champ de la didactique d'une discipline donnée sont transposables à la didactique d'une autre discipline est régulièrement posée par de nombreux chercheurs. Pour notre part, nous avons tenté de répondre à cette question dans le cas particulier du transfert, en didactique de la physique, de quelques concepts mis en oeuvre en didactique des mathématiques pour analyser les processus de conceptualisation. Cette tentative nous a conduits à élaborer un modèle que nous qualifions d'inter - didactique car permettant de modéliser les processus de conceptualisation dans les deux disciplines. Il s'appuie sur les notions de cadre et de registre sémiotique développées de manière spécifique en didactique des mathématiques, et sur une notion nouvelle, celle d'espace de réalité, dont la nécessité s'impose de façon évidente en didactique de la physique, mais dont nous montrons l'utilité en didactique des mathématiques.The issue is repeatedly raised by numerous researchers of determining whether, how and under what conditions, it is possible for concepts developed within the field of the didactics of a given discipline to be transposed to the field of the didactics of another. For our part, we have endeavoured to address this issue in the specific case of the transfer to the didactics of physics of a few concepts developed within the field of the didactics of mathematics, in order to analyse the conceptualisation processes involved. This endeavour led us to develop a model which we terra "inter-didactic" for it allows one to model the conceptualisation processes of both disciplines, This model is based on the notions of semiotic framework and semiotic "register", specifically as these concepts are developed in the didactics of mathematics, as well as on a new notion, that of "spatial view of reality". The need for this new concept imposes itself so to speak, obviously, in the field of physics, but we demonstrate its usefulness in the didactics of mathematics also

Study in inter-didactics of mathematics and physics about acquisition of Ohm's law in high school : change of frame

La loi d'Ohm est une des premières lois physiques écrite sous forme mathématique que les élèves français rencontrent dans leur cursus scolaire. L'obtention de cette relation fonctionnelle par induction à partir d'un nombre discret de mesures repose sur un homomorphisme supposé entre le concept de proportionnalité dans le cadre des mathématiques, et la loi d'Ohm dans le cadre de la physique. Pour comprendre les raisons des difficultés rencontrées par les élèves au cours de cette phase de modélisation, une séquence d'ingénierie didactique a été construite. L'analyse des résultats de cette expérimentation, articulée autour des notions de registre sémiotique, de cadre de rationalité et d'espace de réalité, interprète ces difficultés en termes de rupture de rationalité entre les mathématiques et la physique pour trois éléments particuliers : la dimensionnalité des nombres, le concept de proportionnalité et la différence de nature des règles de validation

Naturally Occurring Carboxypeptidase A6 Mutations: Effect on Enzyme Function and Association with Epilepsy

Carboxypeptidase A6 (CPA6) is a member of the A/B subfamily of M14 metallocarboxypeptidases that is expressed in brain and many other tissues during development. Recently, two mutations in human CPA6 were associated with febrile seizures and/or temporal lobe epilepsy. In this study we screened for additional CPA6 mutations in patients with febrile seizures and focal epilepsy, which encompasses the temporal lobe epilepsy subtype. Mutations found from this analysis as well as CPA6 mutations reported in databases of single nucleotide polymorphisms were further screened by analysis of the modeled proCPA6 protein structure and the functional role of the mutated amino acid. The point mutations predicted to affect activity and/or protein folding were tested by expression of the mutant in HEK293 cells and analysis of the resulting CPA6 protein. Common polymorphisms in CPA6 were also included in this analysis. Several mutations resulted in reduced enzyme activity or CPA6 protein levels in the extracellular matrix. The mutants with reduced extracellular CPA6 protein levels showed normal levels of 50-kDa proCPA6 in the cell, and this could be converted into 37-kDa CPA6 by trypsin, suggesting that protein folding was not greatly affected by the mutations. Interestingly, three of the mutations that reduced extracellular CPA6 protein levels were found in patients with epilepsy. Taken together, these results provide further evidence for the involvement of CPA6 mutations in human epilepsy and reveal additional rare mutations that inactivate CPA6 and could, therefore, also be associated with epileptic phenotypes. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q

Benign familial infantile convulsions (BFIC) are an autosomal-dominant epileptic syndrome characterized by an age of onset within the first year of life. Although they were first reported in families of Italian descent, BFIC have also been described in non-Italian families. We have mapped the BFIC gene to chromosome 19 by linkage analysis in five Italian families with a maximum two-point lod score of 6.36 at D19S114; maximum multipoint lod scores >8 were obtained for the interval D19S250-D19S245. BFIC are therefore the third idiopathic partial epileptic syndrome to be mapped on the human genom

Reproductive Technologies and Genomic Selection in Cattle

The recent development of genomic selection induces dramatic changes in the way genetic selection schemes are to be conducted. This review describes the new context and corresponding needs for genomic based selection schemes and how reproductive technologies can be used to meet those needs. Information brought by reproductive physiology will provide new markers and new improved phenotypes that will increase the efficiency of selection schemes for reproductive traits. In this context, the value of the reproductive techniques including assisted embryo based reproductive technologies (Multiple Ovaluation Embryo Transfer and Ovum pick up associated to in vitro Fertilization) is also revisited. The interest of embryo typing is discussed. The recent results obtained with this emerging technology which are compatible with the use of the last generation of chips for genotype analysis may lead to very promising applications for the breeding industry. The combined use of several embryo based reproductive technologies will probably be more important in the near future to satisfy the needs of genomic selection for increasing the number of candidates and to preserve at the same time genetic variability