Making the MUVE to virtual education

Second Life, a 3D multi-user virtual environment (MUVE), is becoming an increasingly popular topic at educational technology conferences and in the media these days. What’s all the fuss about

Autoreactivity to malondialdehyde-modifications in rheumatoid arthritis is linked to disease activity and synovial pathogenesis

Oxidation-associated malondialdehyde (MDA) modification of proteins can generate immunogenic neo-epitopes that are recognized by autoantibodies. In health, IgM antibodies to MDA-adducts are part of the natural antibody pool, while elevated levels of IgG anti-MDA are associated with inflammatory conditions. Yet, in human autoimmune disease IgG anti-MDA responses have not been well characterized and their potential contribution to disease pathogenesis is not known. Here, we investigate MDA-modifications and anti-MDA-modified protein autoreactivity in rheumatoid arthritis (RA). While RA is primarily associated with autoreactivity to citrullinated antigens, we also observed increases in serum IgG anti-MDA in RA patients compared to controls. IgG anti-MDA levels significantly correlated with disease activity by DAS28-ESR and serum TNF-alpha, IL-6, and CRP. Mass spectrometry analysis of RA synovial tissue identified MDA-modified proteins and revealed shared peptides between MDA-modified and citrullinated actin and vimentin. Furthermore, anti-MDA autoreactivity among synovial B cells was discovered when investigating recombinant monoclonal antibodies (mAbs) cloned from single B cells. Several clones were highly specific for MDA-modification with no cross-reactivity to other antigen modifications. The mAbs recognized MDA-adducts in a variety of proteins. Interestingly, the most reactive clone, originated from an IgG1-bearing memory B cell, was encoded by germline variable genes, and showed similarity to previously reported natural IgM. Other anti-MDA clones display somatic hypermutations and lower reactivity. These anti-MDA antibodies had significant in vitro functional properties and induced enhanced osteoclastogenesis, while the natural antibody related high-reactivity clone did not. We postulate that these may represent distinctly different facets of anti-MDA autoreactive responses

Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts

OBJECTIVES Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed to dissect additional mechanisms by which ACPAs might contribute to development of joint pathology. METHODS Fibroblast-like synoviocytes (FLS) were isolated from the synovial membrane of patients with RA. The FLS cultures were stimulated with polyclonal ACPAs (anti-CCP-2 antibodies) purified from the peripheral blood of patients with RA or with monoclonal ACPAs derived from single synovial fluid B cells. We analysed how ACPAs modulate FLS by measuring cell adhesion and mobility as well as cytokine production. Expression of protein arginine deiminase (PAD) enzymes and protein citrullination were analysed by immunofluorescence, and signal transduction was studied using immunoblotting. RESULTS Challenge of FLS by starvation-induced stress or by exposure to the chemokine interleukin-8 was essential to sensitise the cells to ACPAs. These challenges led to an increased PAD expression and protein citrullination and an ACPA-mediated induction of FLS migration through a mechanism involving phosphoinositide 3-kinase activation. Inhibition of the PAD enzymes or competition with soluble citrullinated proteins or peptides completely abolished the ACPA-induced FLS migration. Different monoclonal ACPAs triggered distinct cellular effects in either fibroblasts or osteoclasts, suggesting unique roles for individual ACPA clones in disease pathogenesis. CONCLUSION We propose that transient synovial insults in the presence of a certain pre-existing ACPA repertoire might result in an ACPA-mediated increase of FLS migration

Unique archaeal assemblages in the Arctic Ocean unveiled by massively parallel tag sequencing

10 páginas, 4 figuras, 1 tabla.The Arctic Ocean plays a critical role in controlling nutrient budgets between the Pacific and Atlantic Ocean. Archaea are key players in the nitrogen cycle and in cycling nutrients, but their community composition has been little studied in the Arctic Ocean. Here, we characterize archaeal assemblages from surface and deep Arctic water masses using massively parallel tag sequencing of the V6 region of the 16S rRNA gene. This approach gave a very high coverage of the natural communities, allowing a precise description of archaeal assemblages. This first taxonomic description of archaeal communities by tag sequencing reported so far shows that it is possible to assign an identity below phylum level to most (95%) of the archaeal V6 tags, and shows that tag sequencing is a powerful tool for resolving the diversity and distribution of specific microbes in the environment. Marine group I Crenarchaeota was overall the most abundant group in the Arctic Ocean and comprised between 27% and 63% of all tags. Group III Euryarchaeota were more abundant in deep-water masses and represented the largest archaeal group in the deep Atlantic layer of the central Arctic Ocean. Coastal surface waters, in turn, harbored more group II Euryarchaeota. Moreover, group II sequences that dominated surface waters were different from the group II sequences detected in deep waters, suggesting functional differences in closely related groups. Our results unveiled for the first time an archaeal community dominated by group III Euryarchaeota and show biogeographical traits for marine Arctic Archaea.P E Galand is supported by a Marie Curie grant (CRENARC MEIF-CT-2007–040247). EO Casamayor was supported by a Spanish grant CGL2006–12058-BOS, and D L Kirchman by NSF OPP ARC-0632233. C Lovejoy would like to acknowledge the support of the Natural Sciences and Engineering Council, Canada (NSERC) Special Research Opportunity Fund. We thank C Pedros-Alio for support during CASES. Deep Arctic samples were collected by K Scarcella and E Didierjean, and we thank the Chief Scientist, Officers and Crew of the CCGS Louis St Laurent and support from Fisheries and Oceans Canada. Tag sequencing was supported by a Keck foundation grant to M Sogin and L Ameral Zettler. This is a contribution to the International Census of Marine Microbes (ICOMM).Peer reviewe

Hydrography shapes bacterial biogeography of the Deep Arctic Ocean

13 páginas, 5 figuras, 2 tablas.It has been long debated as to whether marine microorganisms have a ubiquitous distribution or patterns of biogeography, but recently a consensus for the existence of microbial biogeography is emerging. However, the factors controlling the distribution of marine bacteria remain poorly understood. In this study, we combine pyrosequencing and traditional Sanger sequencing of the 16S rRNA gene to describe in detail bacterial communities from the deep Arctic Ocean. We targeted three separate water masses, from three oceanic basins and show that bacteria in the Arctic Ocean have a biogeography. The biogeographical distribution of bacteria was explained by the hydrography of the Arctic Ocean and subsequent circulation of its water masses. Overall, this first taxonomic description of deep Arctic bacteria communities revealed an abundant presence of SAR11 (Alphaproteobacteria), SAR406, SAR202 (Chloroflexi) and SAR324 (Deltaproteobacteria) clusters. Within each cluster, the abundance of specific phylotypes significantly varied among water masses. Water masses probably act as physical barriers limiting the dispersal and controlling the diversity of bacteria in the ocean. Consequently, marine microbial biogeography involves more than geographical distances, as it is also dynamically associated with oceanic processes. Our ocean scale study suggests that it is essential to consider the coupling between microbial and physical oceanography to fully understand the diversity and function of marine microbes.Financial and ship time support from Fisheries and Oceans Canada and the Canadian International Polar Year Program’s Canada’s Three Oceans project and the Nansen and Amundsen Basins Observational System project. PE Galand was supported by a Marie Curie Grant (CRENARC MEIF-CT-2007-040247) and EO Casamayor by the Spanish Grant CGL2006-12058-BOS. C Lovejoy would like to acknowledge the support of the Natural Sciences and Engineering Council, Canada (NSERC) Special Research Opportunity Fund and ArcticNet. Deep Arctic samples were collected by K Scarcella, E Didierjean and M-E´ Garneau. Pyrosequencing was supported by a Keck foundation grant to M Sogin and L Ameral Zettler. This is a contribution to the International Census of Marine Microbes (ICOMM).Peer reviewe