Un sistema informativo di supporto ad una pianificazione innovativa della sicurezza stradale

Il Safety Manager è un sistema informativo che si basa sull'informatizzazione del processo di analisi e di pianificazione e cerca di migliorare le capacità decisionali dei progettisti durante l'identificazione delle possibili cause di incidentalità e durante la scelta degli interventi più efficaci per uno specifico sito, in base al minor rapporto costi/benefici

Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology

With advances in DNA sequencing technology, it is increasingly common and tractable to informatically look for genes of interest in the genomic databases of parasitic organisms and infer cellular states. Assignment of a putative gene function based on homology to functionally characterized genes in other organisms, though powerful, relies on the implicit assumption of functional homology, i.e. that orthology indicates conserved function. Eukaryotes reveal a dazzling array of cellular features and structural organization, suggesting a concomitant diversity in their underlying molecular machinery. Significantly, examples of novel functions for pre-existing or new paralogues are not uncommon. Do these examples undermine the basic assumption of functional homology, especially in parasitic protists, which are often highly derived? Here we examine the extent to which functional homology exists between organisms spanning the eukaryotic lineage. By comparing membrane trafficking proteins between parasitic protists and traditional model organisms, where direct functional evidence is available, we find that function is indeed largely conserved between orthologues, albeit with significant adaptation arising from the unique biological features within each lineage

A preliminary analysis of in-depth accident data for powered two-wheelers and bicycles in Europe

Despite progress from scientific and technological advancements, road safety remains a major issue worldwide. Road accident impacts such as fatalities, injuries and property damage consist considerable costs borne not only by involved people but society as well. This study aims to present preliminary findings of in-depth accident analysis for two-wheelers (bicycles and powered two wheelers – PTWs) across six countries in Europe. Data regarding the conditions underlying accident occurrence are presented, including time and date, weather, vehicle and road conditions and rider-related parameters such as age, intoxication and use of protective equipment. In addition, a Two Step Cluster Analysis is implemented in order to explore any possible classification of the analysed cases. It appears that two clusters are formed: the first includes more favourable conditions (“no wind, no drugs, good lighting”) while the second consists of less favourable conditions for road safety (“windy, lighting, unknown DUI condition”). This hints at a meaningful separation of the examination of two-wheeler accidents when the influence of outside factors is considerable. The inclusion of different but representative areas across Europe offers robustness and transferability to the data and respective results

SaferWheels study on powered two-wheeler and bicycle accidents in the EU - Annex 6 case summaries

SaferWheels study on powered two-wheeler and bicycle accidents in the EU - Annex 6 case summarie

SaferWheels study on powered two-wheeler and bicycle accidents in the EU - Final report

Road Safety remains a major societal issue within the European Union. In 2014, some 26,000 people died and more than 203,500 were seriously injured on the roads of Europe, i.e. the equivalent of a medium town. However, although there are variations between Member States, road fatalities have been falling throughout the EU. Over the last 20 years, most Member States have achieved an overall reduction, some more than 50%. During this period, research on road safety and accident prevention has predominantly focused on protecting car occupants, with significant results. However, at the same time the number of fatalities and injuries among other categories of road users has not fallen to the same extent, indeed, in some cases, they have risen. The “Vulnerable Road Users” (VRUs) in particular are a priority and represent a real challenge for researchers working on road safety and accident prevention. Accidents involving VRUs comprised approximately 48% of all fatalities in the EU during 2014, with Powered Two-Wheelers (PTWs) comprising 18% and cyclists comprising 8% of the total numbers of fatalities. The Commission adopted in July 2010 its Policy Orientations on Road Safety for 2010-2020. One of the strategic objectifies identified by the Commission is to improve the safety of Vulnerable Road Users. With this category of road users, motorcycle and moped users require specific attention given the trend in the number of accidents involving them and their important share of fatalities and serious injuries. The SaferWheels study was therefore conducted to investigate accident causation for traffic accidents involving powered two-wheelers and bicycles in the European Union. The objective of the study was to gather PTW and bicycle accident data from in-depth crash investigations, obtain accident causation and medical data for those crashes, and to store the information according to an appropriate and efficient protocol enabling a causation-oriented analysis. The expected outcomes were: - Collection of accident data for at least 500 accidents of which approximately 80% would involve Powered Two–Wheelers and the remainder bicycles. Equal numbers of cases were to be gathered in six countries; France, Greece, Italy, the Netherlands, Poland and the UK. - In-depth investigation and reporting for each of the accidents on the basis of the data collected. - Description of the main accident typologies and accident factors. - Proposal of most cost-effective measures to prevent PTW and bicycle accidents

Cathepsin L occupies a vacuolar compartment and is a protein maturase within the endo/exocytic system of Toxoplasma gondii

Regulated exocytosis allows the timely delivery of proteins and other macromolecules precisely when they are needed to fulfil their functions. The intracellular parasite Toxoplasma gondii has one of the most extensive regulated exocytic systems among all unicellular organisms, yet the basis of protein trafficking and proteolytic modification in this system is poorly understood. We demonstrate that a parasite cathepsin protease, TgCPL, occupies a newly recognized va cuolar c ompartment (VAC) that undergoes dynamic fragmentation during T. gondii replication. We also provide evidence that within the VAC or late endosome this protease mediates the proteolytic maturation of proproteins targeted to micronemes, regulated secretory organelles that deliver adhesive proteins to the parasite surface during cell invasion. Our findings suggest that processing of microneme precursors occurs within intermediate endocytic compartments within the exocytic system, indicating an extensive convergence of the endocytic and exocytic pathways in this human parasite.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79312/1/j.1365-2958.2010.07181.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/79312/2/MMI_7181_sm_FigS1-8.pd

Deficiency of a Niemann-Pick, Type C1-related Protein in Toxoplasma Is Associated with Multiple Lipidoses and Increased Pathogenicity

Several proteins that play key roles in cholesterol synthesis, regulation, trafficking and signaling are united by sharing the phylogenetically conserved ‘sterol-sensing domain’ (SSD). The intracellular parasite Toxoplasma possesses at least one gene coding for a protein containing the canonical SSD. We investigated the role of this protein to provide information on lipid regulatory mechanisms in the parasite. The protein sequence predicts an uncharacterized Niemann-Pick, type C1-related protein (NPC1) with significant identity to human NPC1, and it contains many residues implicated in human NPC disease. We named this NPC1-related protein, TgNCR1. Mammalian NPC1 localizes to endo-lysosomes and promotes the movement of sterols and sphingolipids across the membranes of these organelles. Miscoding patient mutations in NPC1 cause overloading of these lipids in endo-lysosomes. TgNCR1, however, lacks endosomal targeting signals, and localizes to flattened vesicles beneath the plasma membrane of Toxoplasma. When expressed in mammalian NPC1 mutant cells and properly addressed to endo-lysosomes, TgNCR1 restores cholesterol and GM1 clearance from these organelles. To clarify the role of TgNCR1 in the parasite, we genetically disrupted NCR1; mutant parasites were viable. Quantitative lipidomic analyses on the ΔNCR1 strain reveal normal cholesterol levels but an overaccumulation of several species of cholesteryl esters, sphingomyelins and ceramides. ΔNCR1 parasites are also characterized by abundant storage lipid bodies and long membranous tubules derived from their parasitophorous vacuoles. Interestingly, these mutants can generate multiple daughters per single mother cell at high frequencies, allowing fast replication in vitro, and they are slightly more virulent in mice than the parental strain. These data suggest that the ΔNCR1 strain has lost the ability to control the intracellular levels of several lipids, which subsequently results in the stimulation of lipid storage, membrane biosynthesis and parasite division. Based on these observations, we ascribe a role for TgNCR1 in lipid homeostasis in Toxoplasma