A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

<p>Abstract</p> <p>Background</p> <p>Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrP^Sc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion.</p> <p>Case presentation</p> <p>We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrP^Scshowed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrP^Scwas estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine.</p> <p>Conclusions</p> <p>A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.</p

Changes in protein expression in mussels Mytilus galloprovincialis dietarily exposed to PVP/PEI coated silver nanoparticles at different seasons

Potential toxic effects of Ag NPs ingested through the food web and depending on the season have not been addressed in marine bivalves. This work aimed to assess differences in protein expression in the digestive gland of female mussels after dietary exposure to Ag NPs in autumn and spring. Mussels were fed daily with microalgae previously exposed for 24 hours to 10 µg/L of PVP/PEI coated 5 nm Ag NPs. After 21 days, mussels significantly accumulated Ag in both seasons and Ag NPs were found within digestive gland cells and gills. Two-dimensional electrophoresis distinguished 104 differentially expressed protein spots in autumn and 142 in spring. Among them, chitinase like protein-3, partial and glyceraldehyde-3-phosphate dehydrogenase, that are involved in amino sugar and nucleotide sugar metabolism, carbon metabolism, glycolysis/gluconeogenesis and the biosynthesis of amino acids KEGG pathways, were overexpressed in autumn but underexpressed in spring. In autumn, pyruvate metabolism, citrate cycle, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism were altered, while in spring, proteins related to the formation of phagosomes and hydrogen peroxide metabolism were differentially expressed. Overall, protein expression signatures depended on season and Ag NPs exposure, suggesting that season significantly influences responses of mussels to NP exposure.This work has been funded by the Spanish Ministry of Economy and Competitiveness (NanoSilverOmics project MAT2012-39372), Basque Government (SAIOTEK project S-PE13UN142 and Consolidated Research Group GIC IT810-13) and the University of the Basque Country UPV/EHU (UFI 11/37 and PhD fellowship to N.D.). This study had also the support of Fundação para a Ciência e Tecnologia (FCT) from Portugal through the Strategic Project UID/MAH00350/2013 granted to CIMA. The contribution of K. Mehennaoui was possible within the project NanoGAM (AFR-PhD-9229040) and M. Mikolaczyk was supported by a PhD fellowship from the French Ministry of Higher Education and Research.info:eu-repo/semantics/acceptedVersio

Multi-objective design of time-constrained bike routes using bio-inspired meta-heuristics

Publisher Copyright: © 2018, Springer International Publishing AG, part of Springer Nature.This paper focuses on the design and implementation of a bike route optimization approach based on multi-objective bio-inspired heuristic solvers. The objective of this approach is to produce a set of Pareto-optimal bike routes that balance the trade-off between the length of the route and its safety level, the latter blending together the slope of the different street segments encompassing the route and their average road velocity. Additionally, an upper and lower restriction is imposed on the time taken to traverse the route, so that the overall system can be utilized for planning bike rides during free leisure time gaps. Instead of designing a discrete route encoding strategy suitable for heuristic operators, this work leverages a proxy software – Open Trip Planner, OTP – capable of computing routes based on three user-level preference factors (i.e. safety, inclination and duration), which eases the adoption of off-the-shelf multi-objective solvers. The system has been assessed in a realistic simulation environments over the city of Bilbao (Spain) using multi-objective bio-inspired approaches. The obtained results are promising, with route sets trading differently distance for safety of utmost utility for bike users to exploit fully their leisure time.Acknowledgments. E. Osaba and J. Del Ser would like to thank the Basque Government for its funding support through the EMAITEK program. This work is also partially funded by Grants TIN2017-86049-R and TIN2014-58304 (Ministerio de Cien-cia e Innovación), and P11-TIC-7529 and P12-TIC-1519 (Plan Andaluz I+D+I).Peer reviewe

Beyond WYSIWYG:sharing contextual sensing data through mmWave V2V communications

Abstract In vehicular scenarios context awareness is a key enabler for road safety. However, the amount of contextual information that can be collected by a vehicle is stringently limited by the sensor technology itself (e.g., line-of-sight, coverage, weather robustness) and by the low bandwidths offered by current wireless vehicular technologies such as DSRC/802.11p. Motivated by the upsurge of research around millimeter-wave vehicle-to-anything (V2X) communications, in this work we propose a distributed vehicle-to-vehicle (V2V) association scheme that considers a quantitative measure of the potential value of the shared contextual information in the pairing process. First, we properly define the utility function of every vehicle balancing classical channel state and queuing state information (CSI/QSI) with context information i.e., sensing content resolution, timeliness and enhanced range of the sensing. Next we solve the problem via a distributed many-to-one matching game in a junction scenario with realistic vehicular mobility traces. It is shown that when receivers are able to leverage information from different sources, the average volume of collected extended sensed information under our proposed scheme is up to 71% more than that of distance and minimum delay-based matching baselines

Multi-Objective Optimization of Bike Routes for Last-Mile Package Delivery with Drop-Offs

Publisher Copyright: © 2018 IEEE.This paper focuses on modeling and solving a last-mile package delivery routing problem with third-party drop-off points. The study is applicable to small or medium-sized delivery companies, which use bikes for performing the routes in an influence area bounded to a city. This routing setup has been formulated as a multi-objective optimization problem, balancing three conflicting objectives: a weighted measure of distance of the route, the safety of the biker, and the economic profit yielded by the delivery of goods to customers. Six different and heterogeneous multi-objective algorithms have been applied to the modeled problem: NSGA-II, MOCell, SMPSO, MOEA/D, NSGA-III and MOMBI2. In order to evaluate the performance of these algorithms, we have devised three experimental setups encompassing different real localizations in Madrid (Spain). For deploying a realistic simulation platform, the open-source Open Trip Planner framework has been used as a proxy evaluator of the produced routes. Results have been compared using the obtained Median and Inter Quartile Range of the hypervolume values reached by the algorithms. Conclusions drawn from this study show that MOCell is the best method for the proposed problem, reaching routes that balance the considered three objectives in a more Pareto-optimal fashion than the rest of counterparts in the benchmark.E. Osaba and J. Del Ser would like to thank the Basque Government for its support through the EMAITEK program. A. J. Nebro is supported by grants TIN2017-86049-R (Spanish Ministry of Education and Science) and P12-TIC-1519 (Plan Andaluz de Investigación, Desarrollo e Innovación).Peer reviewe