Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-beta precursor protein-alpha has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria- related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of alpha-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg2+) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.

Strategies for Power Line Communications Smart Metering Network Deployment

Smart Grids are becoming a reality all over the world. Nowadays, the research efforts for the introduction and deployment of these grids are mainly focused on the development of the field of Smart Metering. This emerging application requires the use of technologies to access the significant number of points of supply (PoS) existing in the grid, covering the Low Voltage (LV) segment with the lowest possible costs. Power Line Communications (PLC) have been extensively used in electricity grids for a variety of purposes and, of late, have been the focus of renewed interest. PLC are really well suited for quick and inexpensive pervasive deployments. However, no LV grid is the same in any electricity company (utility), and the particularities of each grid evolution, architecture, circumstances and materials, makes it a challenge to deploy Smart Metering networks with PLC technologies, with the Smart Grid as an ultimate goal. This paper covers the evolution of Smart Metering networks, together with the evolution of PLC technologies until both worlds have converged to project PLC-enabled Smart Metering networks towards Smart Grid. This paper develops guidelines over a set of strategic aspects of PLC Smart Metering network deployment based on the knowledge gathered on real field; and introduces the future challenges of these networks in their evolution towards the Smart Grid.