The regulation of exosome function in the CNS: implications for neurodegeneration

Exosomes are nanovesicles that have been shown to regulate neuronal development and regeneration, and modulate synaptic function

Il PON Reti e Mobilità e gli obiettivi di Sostenibilità: il ruolo del Piano di Monitoraggio Ambientale

The National Operative Program (PON) “Reti e mobilità” has been approved by European Commission on the 7th of December 2007. The strategic approach of the PON, exclusively devoted to the socalled “convergence regions” of Italy (Campania, Calabria, Sicilia, Puglia), aims to: 1. improve the modal balance by an economic, social and environmental perspective; 2. develop the inter-modality in order to move towards the integration of convergence area into the network of the European transport system; 3. improve the mobility and the accessibility, also to reduce the traffic congestion; 4. increase the efficiency related to security standards, to management techniques and to the quality of transportation services in the sector of freight; 5. guarantee the reduction of environmental impacts through a global improvement of the efficiency of the transport systems. In such a way it is clear that the PON “Reti e mobilità” takes greatly into account the Sustainability principles recognized at European scale as attested by the budget, namely over the 70% of the entire fund, associated with low-impacts infrastructures (railways and harbors). The PON has been submitted to the SEA procedure, following what the 2001/42/CE Directive establishes. The Environmental Report of PON devotes great attention to the monitoring activity as shown by the reported recommendation about the need for adequate measures for the environmental monitoring, also in order to apply corrective measures during the implementation of the program. By this point of view, a first and important step has been the elaboration of the “Environmental Monitoring Plan” (EMP) that represents the main methodological document for the following implementation of the monitoring activity. This paper, after a brief presentation of the program and of the objectives of Sustainability that the Programs aims to pursue through the realization of specific projects, is devoted to introduce the Environmental Monitoring Plan of the PON that has been approved by the Ministry of the Infrastructures and Transport -in charge as Management Authority of the PON- in February 2011. In detail, the PMA represents the tool through which, the Management Authority, that has specific responsibilities and functions in terms of monitoring and environmental assessment of the program, controls the significant impacts on the environment caused by the implementation of the PON and verify the level of achievement of the established objectives of environmental sustainability. The structure of EMP is based on three main aspects: 1) the adoption of the results of other interesting experiences carried out by experts institutions on the topic; 2) an approach favoring the creation of an “integrated” monitoring system with the others Operative Programs activated at regional scale; 3) the implementation of a cooperation and shared process with all the directly-involved actors

Genetic Cross-Interaction between APOE and PRNP in Sporadic Alzheimer's and Creutzfeldt-Jakob Diseases

Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE ε4 allele and homozygosity at polymorphic codon 129 in the PRNP gene are the major genetic risk factors for AD and human prion diseases, respectively. However, the roles of PRNP in AD, and APOE in CJD are controversial. In this work, we investigated for the first time, APOE and PRNP genotypes simultaneously in 474 AD and 175 sporadic CJD (sCJD) patients compared to a common control population of 335 subjects. Differences in genotype distribution between patients and control subjects were studied by logistic regression analysis using age and gender as covariates. The effect size of risk association and synergy factors were calculated using the logistic odds ratio estimates. Our data confirmed that the presence of APOE ε4 allele is associated with a higher risk of developing AD, while homozygosity at PRNP gene constitutes a risk for sCJD. Opposite, we found no association for PRNP with AD, nor for APOE with sCJD. Interestingly, when AD and sCJD patients were stratified according to their respective main risk genes (APOE for AD, and PRNP for sCJD), we found statistically significant associations for the other gene in those strata at higher previous risk. Synergy factor analysis showed a synergistic age-dependent interaction between APOE and PRNP in both AD (SF = 3.59, p = 0.027), and sCJD (SF = 7.26, p = 0.005). We propose that this statistical epistasis can partially explain divergent data from different association studies. Moreover, these results suggest that the genetic interaction between APOE and PRNP may have a biological correlate that is indicative of shared neurodegenerative pathways involved in AD and sCJD

Environmental monitoring of transport infrastructure programs. An Italian experience: the National Operative Program (PON) “Reti e mobilità

The 2001/42/CE Directive on the Strategic Environmental Assessment (SEA) gives environmental monitoring a very important role. Monitoring activities should allow the actual effects of the program to be tested against those predicted in the SEA and help ensure that problems arising during implementation, whether or not they were originally predicted, could be identified and that the appropriate actions could be taken. The few published studies on environmental assessment of transport infrastructure programs highlight different monitoring types and approaches which often are not adequate for the purposes of the SEA Directive. This paper outlines in detail the study carried out for the monitoring of the italian National Operative Program (PON) “Reti e mobilità”, which is co-funded by the European Union in the budgetary period 2007-2013. An innovative approach is discussed. In particular the paper focuses on the governance process, the selection of appropriate indicators to detect and measure changes in environment and the design of a territorial information system based on GIS software solutions (data gathering and processing). Based on the results of the ongoing monitoring activities, some suggestions are provided in order to improve the effectiveness of the SEA monitoring for transport infrastructure programs

Increased levels of acute-phase inflammatory proteins in plasma of patients with sporadic CJD

Objective: Screening plasma samples from patients with sporadic Creutzfeldt-Jakob disease (CJD) to discover diagnostic biomarkers. Methods: Plasma samples were collected from 17 patients with sporadic CJD, 17 patients with Alzheimer disease (AD), and 20 healthy subjects. A 2-phase screening was carried out using quantitative protein mass spectrometry. The putative sporadic CJD biomarkers were then validated independently by immunoturbidimetry. Results: Mass spectrometry uncovered 7 candidate sporadic CJD protein biomarkers, all belonging to the acute-phase response. Highly significant increases of these markers in patients with sporadic CJD, compared with healthy subjects and patients with AD, was confirmed by immunoturbidimetry. Conclusions: The increase in plasma levels of a related set of acute-phase reactants in patients with sporadic CJD is a novel finding that suggests new pathogenetic hypotheses. The possible value of this set of proteins as biomarkers in the diagnosis of sporadic CJD or for blood/tissue donor screening remains to be further explored and validated in larger studies. Neurology (R) 2012;79:1012-101

Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders

BACKGROUND: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary “Genome Clinic Task Force” at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator. METHODS AND RESULTS: We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force. Debate concerning the interpretation of identified variants and the content of the final report constitutes a major part of the task force’s work. Furthermore, issues related to bioethics, genetic counseling, quality control, and reimbursement are also addressed. CONCLUSIONS: This multidisciplinary task force has enabled us to create a platform for regular exchanges between all involved experts in order to deal with the multiple complex issues related to HTS in clinical practice and to continuously improve the diagnostic use of HTS. In addition, this task force was instrumental to formally approve the reimbursement of HTS for molecular diagnosis of Mendelian disorders in Switzerland