“
“The disintegration of the dystrophin-glycoprotein complex represents the initial pathobiochemical insult in Duchenne muscular dystrophy. However, secondary CH5424802 nmr changes in signalling, energy metabolism and ion homeostasis are probably the main factors that eventually cause progressive muscle wasting. Thus, for the proper evaluation of novel therapeutic approaches, it is essential to analyse the reversal of both primary and secondary abnormalities in treated muscles. Antisense

oligomer-mediated exon skipping promises functional restoration of the primary deficiency in dystrophin. In this study, an established phosphorodiamidate morpholino oligomer coupled to a cell-penetrating peptide was employed for the specific removal of exon 23 in the mutated mouse dystrophin gene transcript. Using DIGS analysis, we could show the reversal of secondary pathobiochemical abnormalities in the dystrophic diaphragm following exon-23 skipping. In analogy to the restoration of dystrophin, beta-dystroglycan and neuronal nitric oxide synthase, the muscular dystrophy-associated differential expression of calsequestrin, adenylate kinase, aldolase, mitochondrial creatine kinase and cvHsp was reversed in treated muscle fibres.

Hence, the re-establishment of Dp427 coded by the transcript missing exon 23 has counter-acted dystrophic alterations in Ca(2+)-handling, nucleotide Apoptosis inhibitor metabolism, bioenergetic pathways and cellular stress response. This clearly establishes the exon-skipping approach as a realistic treatment strategy for diminishing diverse downstream alterations in dystrophinopathy.”
“Impulsive people have a strong urge to act without thinking. It is sometimes

regarded as a positive trait but rash impulsiveness is also widely present in clinical disorders such as attention deficit hyperactivity disorder (ADHD), drug dependence, mania, and antisocial behaviour. Contemporary research has begun to make major inroads out into unravelling the brain mechanisms underlying impulsive behaviour with a prominent focus on the limbic cortico-striatal systems. With this progress has come the understanding that impulsivity is a multi-faceted behavioural trait involving neurally and psychologically diverse elements. We discuss the significance of this heterogeneity for clinical disorders expressing impulsive behaviour and the pivotal contribution made by the brain dopamine and serotonin systems in the aetiology and treatment of behavioural syndromes expressing impulsive symptoms. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Current diagnostic methods for skin cancers are based on some morphological characteristics of the pigmented skin lesions, including the geometry of their contour. The aim of this article is to model the early growth of melanoma accounting for the biomechanical characteristics of the tumor microenvironment, and evaluating their influence on the tumor morphology and its evolution.