Brain as the house of autistic soul: current trends in analyzing the risk factors and building up the diagnosis in mild forms of autism spectrum disorder.

The number of children with Autism Spectrum Disorder (ASD) has significantly increased over the last few years. On the one hand, this surge may be associated with increased awareness of this entity and the greater availability of diagnostic tools. On the other hand, influence of factors believed to cause or facilitate ASD development (including environment pollution, stress of modern civilization, brain trauma and use of drugs) could have a negative impact on individuals in the phase of their social and psychological development. Due to the increasing problem, more and more attention is being focused on early detection of ASD, what allows to intervene at the earliest time point. In consequence, the quality of life of ASD-affected people may be significantly improved if diagnosed early. In this review, the list of possible risk factors for ASD is critically appraised and some "pearls for practice", helping in early diagnosis of even mild ASD are outlined.

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

Long-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM.