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

The antecedents and outcomes of creative cognition

This chapter summarises the antecedents and outcomes that are associated with creative potential and creative achievement, as well as the outcomes of creative practice and engagement with the arts. It provides a concise overview of the relationships between creativity and individual or dispositional factors such as intelligence, personality and executive functions, while also exploring the effects of environmental or situational factors, such as reward and evaluation, on creativity and motivation with an especial focus on two important outcomes of creative cognition, academic achievement and wellbeing. The consequences associated with engagement in creative practice and arts-integrated teaching are also discussed

High-order sliding mode control of a DC motor drive via a switched controlled multi-cellular converter

In this article, we present a high-order sliding mode controller of a DC motor drive connected to a multi-cellular converter. More specifically, we design a second-order (super-twisting) control algorithm for the speed regulation of a DC motor. For this, a switching control for the multi-cellular converter is derived in order to supply the correct reference value for the speed regulation. A practical implementation of the controller is realised using a laboratory set-up. The performance and the validity of the controller are shown experimentally

Ferritin and hemocyanin: 210Po molecular traps in marine fish, oyster and lobster

International audienceThe relative degree of binding of 210Po with fish, mollusc and crustacean ferritins was investigated. Comparison of 210Po concentrations in the purified ferritins from liver of the Atlantic mackerel Scomber scombrus and from the visceral mass of oysters Crassostrea gigas confirmed the high affinity of polonium for these iron-containing proteins. The ferritin fraction in lobster Homarus gammarus hepatopancreas contained an order of magnitude more 210Po than pure ferritin from fish and oyster; however, the hepatopancreatic ferritin fraction was not pure and it also contained the respiratory protein hemocyanin. A high performance size-exclusion chromatography analysis further revealed the important contribution of hemocyanin to 210Po fixation in lobster. The combined 210Po binding capacity of ferritin and hemocyanin in lobster hepatopancreas most probably accounts for the very high 210Po concentrations found in the hepatopancreas of many higher crustaceans

Comparative radiotracer study of cadmium uptake, storage, detoxification and depuration in the oyster Crassostrea gigas: potential adaptive mechanisms

International audienceThe bioaccumulation of cadmium in the oyster Crassostrea gigas originating from a clean (Bourgneuf Bay) and a chronically Cd-contaminated area (Gironde estuary) experimentally exposed to 109Cd-labeled bulk seawater (dissolved and particulate pathways combined) was examined over 21 d. A single-component first-order kinetic model describing the behavior of the bioaccumulation factor (BAF) throughout the experiment showed that the estimated Cd BAF at 21 d was 47% higher for oysters originating from the contaminated estuary than for oysters from the clean area, suggesting an influence of the previous chronic exposure to Cd contamination in the estuarine environment. From the experimental results, the potential adaptive mechanism suggested cannot be attributed to a reduction in Cd permeability but rather to a higher Cd turnover due to the synergy between lysosomes and metallothioneins which, through chelation, are responsible for the reduction in bioavailability and toxicity of cd in oysters. The lower BAF observed for soft parts of oysters previously exposed to chronic Cd contamination corresponded to a faster response to the experimental Cd contamination due to the presence of pre-existing metallothioneins induced by the Cd present in the estuarine environment. Furthermore, based on a 2-component exponential loss kinetic model, Cd complexation to metallothioneins and lysosomes was probably responsible for the slow turnover in the long-term compartment of loss (biological half-life, Tb1/2 = 495 and 198 d for the Bourgneuf and the Gironde oysters, respectively). Of the total Cd accumulated, 40 to 60% was in the soluble form and 30 to 40% of this fraction had been detoxified by the Gironde oysters through chelation to metallothioneins or to lysosomes, which means that approximately 12 to 24% of the total Cd accumulated was potentially bioavailable to humans through oyster consumption. However, through depuration, it was also more efficiently eliminated from oyster soft parts (the edible portion) previously exposed to Cd than from control oysters. Therefore, in the light of these results, it is suggested that the way in which regulatory thresholds of Cd in oysters are presently calculated should be reconsidered and should take into account the level of Cd already detoxified by the oysters through complexation processes