1. Salomon RG, Hong L, Hollyfield J. {{The Discovery of Carboxyethylpyrroles (CEPs): Critical Insights into AMD, Autism, Cancer, and Wound Healing from Basic Research on the Chemistry of Oxidized Phospholipids}}. {Chem Res Toxicol};2011 (Aug 26)
Basic research, exploring the hypothesis that 2-(omega-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modification of protein lysyl epsilon-amino groups by gamma-hydroxyalkenal phospholipids that are formed by oxidative cleavage of docosahexaenoyl of phospholipids. Chemical synthesis of CEP-modified proteins and the production of highly specific antibodies that recognize them preceded and facilitated their detection in vivo and enabled exploration of their biological occurrence and activities. This investigational approach – from the chemistry of biomolecules to disease phenotype – is proving remarkably productive.
Lien vers le texte intégral (Open Access ou abonnement)
2. Thomas MS, Knowland VC, Karmiloff-Smith A. {{Mechanisms of developmental regression in autism and the broader phenotype: A neural network modeling approach}}. {Psychol Rev};2011 (Aug 29)
Loss of previously established behaviors in early childhood constitutes a markedly atypical developmental trajectory. It is found almost uniquely in autism and its cause is currently unknown (Baird et al., 2008). We present an artificial neural network model of developmental regression, exploring the hypothesis that regression is caused by overaggressive synaptic pruning and identifying the mechanisms involved. We used a novel population-modeling technique to investigate developmental deficits, in which both neurocomputational parameters and the learning environment were varied across a large number of simulated individuals. Regression was generated by the atypical setting of a single pruning-related parameter. We observed a probabilistic relationship between the atypical pruning parameter and the presence of regression, as well as variability in the onset, severity, behavioral specificity, and recovery from regression. Other neurocomputational parameters that varied across the population modulated the risk that an individual would show regression. We considered a further hypothesis that behavioral regression may index an underlying anomaly characterizing the broader autism phenotype. If this is the case, we show how the model also accounts for several additional findings: shared gene variants between autism and language impairment (Vernes et al., 2008); larger brain size in autism but only in early development (Redcay & Courchesne, 2005); and the possibility of quasi-autism, caused by extreme environmental deprivation (Rutter et al., 1999). We make a novel prediction that the earliest developmental symptoms in the emergence of autism should be sensory and motor rather than social and review empirical data offering preliminary support for this prediction. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
