Brain Transcriptional and Epigenetic Associations with Autism

BackgroundAutism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic.Conclusions/SignificanceThis work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.     

How Does Our Motor System Determine Its Learning Rate?

Motor learning is driven by movement errors. The speed of learning can be quantified by the learning rate, which is the proportion of an error that is corrected for in the planning of the next movement. Previous studies have shown that the learning rate depends on the reliability of the error signal and on the uncertainty of the motor system’s own state. These dependences are in agreement with the predictions of the Kalman filter, which is a state estimator that can be used to determine the optimal learning rate for each movement such that the expected movement error is minimized. Here we test whether not only the average behaviour is optimal, as the previous studies showed, but if the learning rate is chosen optimally in every individual movement. Subjects made repeated movements to visual targets with their unseen hand. They received visual feedback about their endpoint error immediately after each movement. The reliability of these error-signals was varied across three conditions. The results are inconsistent with the predictions of the Kalman filter because correction for large errors in the beginning of a series of movements to a fixed target was not as fast as predicted and the learning rates for the extent and the direction of the movements did not differ in the way predicted by the Kalman filter. Instead, a simpler model that uses the same learning rate for all movements with the same error-signal reliability can explain the data. We conclude that our brain does not apply state estimation to determine the optimal planning correction for every individual movement, but it employs a simpler strategy of using a fixed learning rate for all movements with the same level of error-signal reliability.     

Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturation.

In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood.     

Qualité et interprétation des examens du bilan biologique de thrombophilie constitutionnelle Cas particulier des principaux inhibiteurs: antithrombine, protéine C et protéine S

Biological screening for hereditary thrombophilia must be performed with constant concern for quality of the results and the interpretation. Different guidelines are available common to most laboratory tests, common to hemostasis tests, thrombophilia screening or specific for each test. These different steps are discussed in this paper with a special focus on the diagnosis of antithrombin, protein C and protein S deficiencies.