An NLRP3 Mutation Causes Arthropathy and Osteoporosis in Humanized Mice

The NLRP3 inflammasome plays a critical role in host defense by facilitating caspase I activation and maturation of IL-1β and IL-18, whereas dysregulation of inflammasome activity results in autoinflammatory disease. Factors regulating human NLRP3 activity that contribute to the phenotypic heterogeneity of NLRP3-related diseases have largely been inferred from the study of Nlrp3 mutant mice. By generating a mouse line in which the NLRP3 locus is humanized by syntenic replacement, we show the functioning of the human NLRP3 proteins in vivo, demonstrating the ability of the human inflammasome to orchestrate immune reactions in response to innate stimuli. Humanized mice expressing disease-associated mutations develop normally but display acute sensitivity to endotoxin and develop progressive and debilitating arthritis characterized by granulocytic infiltrates, elevated cytokines, erosion of bones, and osteoporosis. This NLRP3-dependent arthritis model provides a platform for testing therapeutic reagents targeting the human inflammasome

Improving merge methods for grid-based digital elevation models

Digital Elevation Models (DEMs) are used to represent the terrain in applications such as, for example, overland flow modelling or viewshed analysis. DEMs generated from digitising contour lines or obtained by LiDAR or satellite data are now widely available. However, in some cases, the area of study is covered by more than one of the available elevation data sets. In these cases the relevant DEMs may need to be merged. The merged DEM must retain the most accurate elevation information available while generating consistent slopes and aspects. In this paper we present a thorough analysis of three conventional grid-based DEM merging methods that are available in commercial GIS software. These methods are evaluated for their applicability in merging DEMs and, based on evaluation results, a method for improving the merging of grid-based DEMs is proposed. DEMs generated by the proposed method, called Id:Blend, showed significant improvements when compared to DEMs produced by the three conventional methods in terms of elevation, slope and aspect accuracy, ensuring also smooth elevation transitions between the original DEMs. The results produced by the improved method are highly relevant different applications in terrain analysis, e.g., visibility, or spotting irregularities in landforms and for modelling terrain phenomena, such as overland flow

Data descriptor: a global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. (TABLE) Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike

Microscopie par rayons X dans la fenêtre de l'eau : faisabilité et intérêt pour la biologie d'un instrument de laboratoire

La biologie étudie des structures ou des phénomènes sub-cellulaires. Pour cela la microscopie est la technique d'observation privilégiée. La résolution spatiale de la microscopie optique s'avère bien souvent insuffisante pour de telles observations. Les techniques plus résolvantes, comme la microscopie électronique par transmission sont souvent destructrices et d'une complexité peu adaptée aux besoins des biologistes. La microscopie par rayons X dans la fenêtre de l'eau permet l'imagerie rapide de cellules dans leur milieu naturel, nécessite peu de préparation et offre des résolutions de quelques dizaines de nanomètres. De plus, il existe un bon contraste naturel entre les structures carbonées (protéines, lipides) et l'eau. Actuellement cette technique est limitée aux centres de rayonnement synchrotron, ce qui impose une planification et des déplacements incompatibles avec les besoins de la biologie. Un tel microscope fonctionnant avec uns source de laboratoire serait d'une grande utilité. Ce document présente un état de l'art de la microscopie par rayons X dans la fenêtre de l'eau. Un cahier des charges détaillé pour un appareil de laboratoire ayant les performances optiques requises par les biologistes est présenté et confronté aux microscopes X de laboratoire déjà existants. Des solutions concernant la source et les optiques sont également discutées

Forvaltning av mindre vassdrag i lys av Vannrammedirektivet - Gjevingvassdraget i Tvedestrand

I Aust-Agder har Tvedestrand kommune, Fylkesmannen i Aust-Agder og NIVA samarbeidet om et pilotprosjekt i det lille Gjevingvassdraget med sjøområdet utenfor (Lyngørfjorden) for å skaffe erfaring med implementering av Vannrammedirektivet på regionalt og lokalt nivå. Vassdraget og sjøområdet er geografisk avgrenset i forhold til andre lokalområder og innenfor et antatt vannområde og nedbørfeltdistrikt. Vannforekomstene er typifisert og det er gjennomført kjemiske og biologiske undersøkelser for å vurdere økologisk status. På denne bakgrunn og etter en kartlegging og kvantifisering av påvirkninger ble de viktigste vannforekomster karakterisert som: a) ”not at risk”, b) ”possibly at risk” eller c) ”at risk”. De fleste innsjølokaliteter er ”at risk” i dette vassdraget, mens Gjevingelva er ”not at risk”. Årsakene til karakteriseringen ”at risk” er påvirkning av sur nedbør i høyereliggende innsjøer og spredning av den fremmede fiskearten gjedde i hovedvassdragets innsjøer. De oppnår dermed ikke ”god økologisk status”, slik det kreves i Vannrammedirektivet. Sjøområdet er karakterisert som ”possibly at risk” blant annet pga oksygensvinn i bunnvannet