Construction and reconstruction of brain circuits: normal and pathological axon guidance

Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the central nervous system (CNS) as well as the peripheral nervous system (PNS) must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, whilst these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here, we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields

Scientific Assessment of Ozone Depletion: 2010, Chapter 2 - Stratospheric Ozone and Surface Ultraviolet Radiation

As a result of the Montreal Protocol, ozone is expected to recover from the effect of ozone-depleting substances (ODSs) as their abundances decline in the coming decades. The 2006 Assessment showed that globally averaged column ozone ceased to decline around 1996, meeting the criterion for the first stage of recovery. Ozone is expected to increase as a result of continued decrease in ODSs (second stage of recovery). This chapter discusses recent observations of ozone and ultraviolet radiation in the context of their historical records. Natural variability, observational uncertainty, and stratospheric cooling necessitate a long record in order to attribute an ozone increase to decreases in ODSs. The primary tools used in this Assessment for prediction of ozone are chemistry-climate models (CCMs). These CCMs are designed to represent the processes determining the amount of stratospheric ozone and its response to changes in ODSs and greenhouse gases. Eighteen CCMs have been recently evaluated using a variety of process-based compari-sons to measurements. The CCMs are further evaluated here by comparison of trends calculated from measurements with trends calculated from simulations designed to reproduce ozone behavior during an observing period

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold >= 7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators.Cardiolog