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BackgroundIron accumulates in the brain during aging and is the focus of intensive research as an abnormal load, particularly in Deep Gray Matter (DGM), is related to neurodegeneration. Magnetic Resonance Imaging (MRI) metrics such as Quantitative Susceptibility Mapping (QSM) and apparent transverse relaxation rate R2* can be used to follow up iron in vivo. While the influence of age and sex on iron levels has already been reported, a careful consideration of neuronal risk factors, as well as for an enhanced sensitivity, is needed to define the normal evolution.MethodsQSM and R2* at ultra-high field MRI are used to study iron in DGM using a carefully-characterized cohort of the healthy aging brain (SENIOR). Seventy-seven cognitively healthy elders (from 54 to 78 y/o) with clinical, biology, genetics, and cardiovascular risk factors careful evaluation. Differences linked with age, sex, cardiovascular risk factors and weight are studied.ResultsAge and sex have an influence on the brain iron deposition measured by QSM and R2* in a context of normal aging, without appearance of a pathological neurodegenerative process. Iron deposition shows higher values in the caudate and the putamen in older participants. Female participants present a higher level of iron in the amygdala, and males in the thalamus. Female participants also present differences in the accumbens, caudate and hippocampus when evaluating the joint age and sex effect. Participants with higher cardiovascular risk factors showed higher values of the iron, even without any impairment in their cognitive capability. An overweight is related with a higher iron load in the putamen for QSM and R2* in female participants. We controlled that these modifications of iron deposition are not related to a specific profile in the genotype of ApoE loci.ConclusionsEstablishing baseline values of QSM and R2* as iron probes in the context of aging is essential to determine differences in the process of neurodegeneration. Age and sex of participants are important factors that affect brain iron normal values. On the other hand, the presence of cardiovascular risk factors, which can be associated with age related diseases, can also potentially be linked with the iron deposition in the brain.

OpenStreetMap (OSM) is among the most prominent Volunteered Geographic Information (VGI) initiatives, aiming to create a freely accessible world map. Despite its success, the data quality of OSM remains variable. This study begins by identifying the quality metrics proposed by earlier research to assess the quality of OSM building footprints. It then evaluates the quality of OSM building data from 2018 and 2023 for five cities within Québec, Canada. The analysis reveals a significant quality improvement over time. In 2018, the completeness of OSM building footprints in the examined cities averaged around 5%, while by 2023, it had increased to approximately 35%. However, this improvement was not evenly distributed. For example, Shawinigan saw its completeness surge from 2% to 99%. The study also finds that OSM contributors were more likely to digitize larger buildings before smaller ones. Positional accuracy saw enhancement, with the average error shrinking from 3.7 m in 2018 to 2.3 m in 2023. The average distance measure suggests a modest increase in shape accuracy over the same period. Overall, while the quality of OSM building footprints has indeed improved, this study shows that the extent of the improvement varied significantly across different cities. Shawinigan experienced a substantial increase in data quality compared to its counterparts.

Numerous viruses use a portal system for dsDNA entry and exit from their capsid. Here the authors report the atomic structure of phage SPP1 portal DNA gatekeeper and its mechanism of assembly. They also identify evolution breakpoints between different tailed bacteriophages morphotypes and herpesviruses.

Mokola virus (MOKV) belongs to the lyssavirus genus. As other genus members-including rabies virus (RABV)-it causes deadly encephalitis in mammals. MOKV entry into host cells is mediated by its transmembrane glycoprotein G. First, G binds cellular receptors, triggering virion endocytosis. Then, in the acidic endosomal environment, G undergoes a conformational change from its pre- toward its post-fusion state that catalyzes the merger of the viral and endosomal membranes. Here, we have determined the crystal structure of a soluble MOKV G ectodomain in which the hydrophobic fusion loops have been replaced by more hydrophilic sequences. The crystal structure corresponds to a monomer that is similar to the protomer of the trimeric post-fusion state of vesicular stomatitis virus (VSV) G. However, by electron microscopy, we show that, at low pH, at the surface of pseudotyped VSV, MOKV spikes adopt the trimeric post-fusion conformation and have a tendency to reorganize into regular arrays. Sequence alignment between MOKV G and RABV G allows a precise location of RABV G antigenic sites. Repositioning MOKV G domains on VSV G pre-fusion structure reveals that antigenic sites are located in the most exposed part of the molecule in its pre-fusion conformation and are therefore very accessible to antibodies. Furthermore, the structure allows the identification of pH-sensitive molecular switches. Specifically, the long helix, which constitutes the core of the post-fusion trimer for class III fusion glycoproteins, contains many acidic residues located at the trimeric interface. Several of them, aligned along the helix, point toward the trimer axis. They have to be protonated for the post-fusion trimer to be stable. At high pH, when they are negatively charged, they destabilize the interface, which explains the conformational change reversibility. Finally, the present structure will be of great help to perform rational mutagenesis on lyssavirus glycoproteins.

The wayfinding feature highly contributed to the rise of cartographic platforms. However, no study really focused on the way these tools are both used and perceived in a wayfinding context. The qualitative investigation we conducted on 30 users of such platforms suggests that the related uses depend on – at least – two mental models: the first one assumes that the cartographic platform is a digital extension of paper maps, while the other one likens it to a GPS system.

The number of people registering in an online community depends on two main factors: interest in, and awareness of, the project. Registering to a project does not, however, imply contributing to it, as lacking the knowledge and skills can be a barrier to participation. In order to identify the nature of events that might have facilitated or hindered enrollments in the OpenStreetMap (OSM) project over time, we analyzed the correlations between the number of new participants and the events that dotted its history. Four different metrics were defined to characterize participants’ behaviors: the daily number of registrations, the daily number of participants that made a first contribution, the delays between contributors’ registration and their first edits, and a daily contribution ratio built from the number of new contributors and the number of new registered members. Time series analyses were used to identify trends, and outstanding variations of the number of participants. An inventory of events that took place along the OSM project’s history was created and appreciable variations of the metrics have been linked to events that seemed to be meaningful. Although a correlation does not imply causality, many of the explanations these correlations suggest are supported by the results of other studies, either directly or indirectly. For instance, when considering the time participants spend as “lurker”, as well as on the nature of the contribution of early participants. In other cases, they suggest new explanations for the origin of the spam accounts that affect registration statistics, or the decline in the proportion of registered members who actually become contributors.

Proteomic technologies have been recently adapted to the new field of clinical proteomics. The origin of errors and biases has been well-identified in the pre-analytical steps, leading to the measurement of clinical analytes. One possible source of inadequacy in clinical proteomics is linked to sample pooling. This practice is usually related to low sample availability, variability, experiment time/cost. In this study, we first asked whether sample pooling in top–down proteomics is suitable to obtain a relevant biological average. Our second objective was to identify inflammatory biomarkers of outlier samples in our population of Creutzfeldt-Jakob disease patients. Our results demonstrated that, in a proteomics study, sample pooling as well as the inflammation status was an important source of errors: missed detection of biomarkers and false identification of others. Pooled samples were not equivalent to the average of biological values. In addition, this procedure reduced the statistical value of the identified biomarkers due to a stabilization of their standard deviation and rendered outlier samples difficult to detect. We identified serum amyloid A as a candidate biomarker of outlier samples. The presence of this protein, which could be explained by inflammatory processes, induced major modifications in the sample profiles.

Research in the area of spatial cognition demonstrated that references to landmarks are essential in the communication and the interpretation of wayfinding instructions for human being. In order to detect landmarks, a model for the assessment of their salience has been previously developed by Raubal and Winter. According to their model, landmark salience is divided into three categories: visual, structural, and semantic. Several solutions have been proposed to automatically detect landmarks on the basis of these categories. Due to a lack of relevant data, semantic salience has been frequently reduced to objects’ historical and cultural significance. Social dimension (i.e., the way an object is practiced and recognized by a person or a group of people) is systematically excluded from the measure of landmark semantic salience even though it represents an important component. Since the advent of mobile Internet and smartphones, the production of geolocated content from social web platforms—also described as geosocial data—became commonplace. Actually, these data allow us to have a better understanding of the local geographic knowledge. Therefore, we argue that geosocial data, especially Social Location Sharing datasets, represent a reliable source of information to precisely measure landmark semantic salience in urban area.

As an emerging complex concept, GeoDesign requires an innovative theoretical basis, tools, supports and practices. For this reason, we propose a new concept, “WikiGIS”, designed to answer some dimensions of the GeoDesign process. WikiGIS focuses on the needs of GeoDesign, but we leave the door open for future improvement when tested in other areas that may have additional needs. WikiGIS is built on Web 2.0 technologies—and primarily on wiki—to manage the tracking of participants’ editing (i.e., managing the contributions history). It also offers GIS functions for geoprocessing and a design-based approach for sketching proposals. One of the main strengths of WikiGIS is its ability to manage the traceability of contributions with an easy and dynamical access, data quality and deltification. The core of this paper consists of presenting a conceptual framework for WikiGIS using UML diagrams. A user interface is presented later to show how our WikiGIS proposal works. This interface is simply a means to illustrate the concepts underlying WikiGIS.

Tungsten was chosen as a wall component to interact with the plasma generated by the International Thermonuclear Experimental fusion Reactor (ITER). Nevertheless, during plasma operation tritiated tungsten nanoparticles (W-NPs) will be formed and potentially released into the environment following a Loss-Of-Vacuum-Accident, causing occupational or accidental exposure. We therefore investigated, in the bronchial human-derived BEAS-2B cell line, the cytotoxic and epigenotoxic effects of two types of ITER-like W-NPs (plasma sputtering or laser ablation), in their pristine, hydrogenated, and tritiated forms. Long exposures (24 h) induced significant cytotoxicity, especially for the hydrogenated ones. Plasma W-NPs impaired cytostasis more severely than the laser ones and both types and forms of W-NPs induced significant micronuclei formation, as shown by cytokinesis-block micronucleus assay. Single DNA strand breaks, potentially triggered by oxidative stress, occurred upon exposure to W-NPs and independently of their form, as observed by alkaline comet assay. After 24 h it was shown that more than 50% of W was dissolved via oxidative dissolution. Overall, our results indicate that W-NPs can affect the in vitro viability of BEAS-2B cells and induce epigenotoxic alterations. We could not observe significant differences between plasma and laser W-NPs so their toxicity might not be triggered by the synthesis method.

With the emergence of Web 2.0, new applications arise and evolve into more interactive forms of collective intelligence. These applications offer to both professionals and citizens an open and expanded access to geographic information. In this paper, we develop the conceptual foundations of a new technology solution called WikiGIS. WikiGIS’s strength lies in its ability to ensure the traceability of changes in spatial-temporal geographic components (geometric location and shape, graphics: iconography and descriptive) generated by users. The final use case highlights to what extent WikiGIS could be a relevant and useful technological innovation in Geocollaboration.

Place, as a concept, is subject to a lively, ongoing discussion involving different disciplines. However, most of these discussions approach the issue without a geographic perspective, which is the natural habitat of a place. This study contributes to this discourse through the exploratory examination of urban intelligence utilizing the geographical relationship between sense of place and social capital at the collective and individual level. Using spatial data collected through a web map-based survey, we perform an exhaustive examination of the spatial relationship between sense of place and social capital. We found a significant association between sense of place and social capital from a spatial point of view. Sense of place and social capital spatial dimensions obtain a non-disjoint relationship for approximately half of the participants and a spatial clustering when they are aggregated. This research offers a new exploratory perspective for place studies in the context of cities, and simultaneously attempts to depict a platial–social network based on sense of place and social capital, which cities currently lack.

BACKGROUND:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. METHODS:Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. RESULTS:During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. CONCLUSIONS:This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.

Online collaborative communities are now ubiquitous. Identifying the nature of the events that drive contributors to withdraw from a project is of prime importance to ensure the sustainability of those communities. Previous studies used ad hoc criteria to identify withdrawn contributors, preventing comparisons between results and introducing interpretation biases. This paper compares different methods to identify withdrawn contributors, proposing a probabilistic approach. Withdrawals from the OpenStreetMap (OSM) community are investigated using time series and survival analyses. Survival analysis revealed that participants’ withdrawal pattern compares with the life cycles studied in reliability engineering. For OSM contributors, this life cycle would translate into three phases: “evaluation,” “engagement” and “detachment.” Time series analysis, when compared with the different events that may have affected the motivation of OSM participants over time, showed that an internal conflict about a license change was related to largest bursts of withdrawals in the history of the OSM project. This paper not only illustrates a formal approach to assess withdrawals from online communities, but also sheds new light on contributors’ behavior, their life cycle, and events that may affect the length of their participation in such project.

Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformational changes of viral glycoproteins. Crystal structures provide static pictures of pre- and post-fusion conformations of these proteins but the transition pathway remains elusive. Here, using several biophysical techniques, including analytical ultracentrifugation, circular dichroïsm, electron microscopy and small angle X-ray scattering, we have characterized the low-pH-induced fusogenic structural transition of a soluble form of vesicular stomatitis virus (VSV) glycoprotein G ectodomain (G(th), aa residues 1-422, the fragment that was previously crystallized). While the post-fusion trimer is the major species detected at low pH, the pre-fusion trimer is not detected in solution. Rather, at high pH, G(th) is a flexible monomer that explores a large conformational space. The monomeric population exhibits a marked pH-dependence and adopts more elongated conformations when pH decreases. Furthermore, large relative movements of domains are detected in absence of significant secondary structure modification. Solution studies are complemented by electron micrographs of negatively stained viral particles in which monomeric ectodomains of G are observed at the viral surface at both pH 7.5 and pH 6.7. We propose that the monomers are intermediates during the conformational change and thus that VSV G trimers dissociate at the viral surface during the structural transition.

Convergence of GIS with ICT (Internet, mobile phone) and geolocation systems (GPS) has now resulted in the emergence of a new form of Web- mapping based on techniques and principles of Web 2.0. Driven by information technologies, mapping traditionally reserved for professionals is now taking place in our daily practices. Beyond a marketing artifact, the « Web-mapping 2.0 » which allows the general public to read and write maps raises many questions about the (potential) place of amateurs into professional processes (updated databases, field collection, production of collaborative base maps, etc.). This article focuses on the acquisition of geographical knowledge through amateurs. More specifically, it explores the potential of Web-mapping 2.0 for citizen science, a term used to describe the involvement of citizens in the process of gathering scientific data.

Pur-α is a nucleic acid-binding protein involved in cell cycle control, transcription, and neuronal function. Initially no prediction of the three-dimensional structure of Pur-α was possible. However, recently we solved the X-ray structure of Pur-α from the fruitfly Drosophila melanogaster and showed that it contains a so-called PUR domain. Here we explain how we exploited bioinformatics tools in combination with X-ray structure determination of a bacterial homolog to obtain diffracting crystals and the high-resolution structure of Drosophila Pur-α. First, we used sensitive methods for remote-homology detection to find three repetitive regions in Pur-α. We realized that our lack of understanding how these repeats interact to form a globular domain was a major problem for crystallization and structure determination. With our information on the repeat motifs we then identified a distant bacterial homolog that contains only one repeat. We determined the bacterial crystal structure and found that two of the repeats interact to form a globular domain. Based on this bacterial structure, we calculated a computational model of the eukaryotic protein. The model allowed us to design a crystallizable fragment and to determine the structure of Drosophila Pur-α. Key for success was the fact that single repeats of the bacterial protein self-assembled into a globular domain, instructing us on the number and boundaries of repeats to be included for crystallization trials with the eukaryotic protein. This study demonstrates that the simpler structural domain arrangement of a distant prokaryotic protein can guide the design of eukaryotic crystallization constructs. Since many eukaryotic proteins contain multiple repeats or repeating domains, this approach might be instructive for structural studies of a range of proteins.

For a few years now, several development projects have been carried out in municipal contexts in order to make spatial information available on the Internet. An overall observation of the existing municipal Web sites obviously shows the great variety of the objectives at stake, and of the technological solutions implemented. Despite the increasing number of researches dealing with the democratization of e-information addressed to citizens and e-governments, it is still difficult to clearly identify the current privileged means of communication between cities and citizens on the basis of cartographic data. This difficulty is related to the absence of formal and effective frameworks to characterize and classify the various ways to diffuse geospatial information on municipal Web sites. On the basis of the above, the present research aims at remedying this ignorance by elaborating a new classification framework to effectively describe GIS-based Web sites in municipal contexts. The adopted strategy consists in analysing the already existing partial approaches of classification, in order to pursue with the development of a more comprehensive pragmatic classification framework. This framework is then the subject of an experimentation consisting of a detailed analysis of the contents and functioning of a hundred existing municipal Web sites in Canada. Finally, this experimentation makes it possible to draw initial conclusions regarding the usability of the new classification mode proposed, as well as to identify some further research pathways.