Fine-Mapping Resolves Eae23 into Two QTLs and Implicates ZEB1 as a Candidate Gene Regulating Experimental Neuroinflammation in Rat

This study was supported by grants from the Swedish Research Council, The Wadsworth Foundation, Söderbergs Foundation, Petrus and Augusta Hedlunds Foundation, Bibbi and Niels Jensens Foundation, Montel Williams Foundation, Åke-Wibergs Stiftelse, the Swedish Foundation for Neurologically Disabled and the EU 6TH Framework EURATools (LSHG-CT-2005-019015) and Neuropromise (LSHM-CT-2005-018637)

Adaptive and maladaptive consequences of “matching habitat choice:” lessons from a rapidly-evolving butterfly metapopulation

Relationships between biased dispersal and local adaptation are currently debated. Here, I show how prior work on wild butterflies casts a novel light on this topic. “Preference” is defined as the set of likelihoods of accepting particular resources after encountering them. So defined, butterfly oviposition preferences are heritable habitat adaptations distinct from both habitat preference and biased dispersal, but influencing both processes. When a butterfly emigrates after its oviposition preference begins to reduce realized fecundity, the resulting biased dispersal is analogous to that occurring when a fish emigrates after its morphological habitat adaptations reduce its feeding rate. I illustrate preference-biased dispersal with examples from metapopulations of Melitaea cinxia and Euphydryas editha. E. editha were feeding on a well-defended host, Pedicularis, when humans created patches in which Pedicularis was killed and a less-defended host, Collinsia, was rendered phenologically available. Patch-specific natural selection favoured oviposition on Collinsia in logged (“clearing”) patches and on Pedicularis in undisturbed open forest. Quantitative variation in post-alighting oviposition preference was heritable, and evolved to be consistently different between patch types. This difference was driven more by biased dispersal than by spatial variation of natural selection. Insects developing on Collinsia in clearings retained adaptations to Pedicularis in clutch size, geotaxis and oviposition preference, forcing them to choose between emigrating in search of forest habitats with Pedicularis or staying and failing to find their preferred host. Insects that stayed suffered reduction of realized fecundity after delayed oviposition on Collinsia. Those that emigrated suffered even greater fitness penalty from consistently low offspring survival on Pedicularis. Paradoxically, most emigrants reduced both their own fitness and that of the recipient populations by dispersing from a benign natal habitat to which they were maladapted into a more demanding habitat to which they were well-adapted. “Matching habitat choice” reduced fitness when evolutionary lag rendered traditional cues unreliable in a changing environment

Contrasting effects of habitat area and connectivity on evenness of pollinator communities

Losses of both habitat area and connectivity have been identified as important drivers of species richness declines, but little theoretical and empirical work exists that addresses the effect of fragmentation on relative commonness of highly mobile species such as pollinating insects. With a large dataset of wild bee and butterfly abundances collected across Europe, we first tested the effect of habitat area and connectivity on evenness in pollinator communities using a large array of indexes that give different weight to dominance and rarity. Second, we tested if traits related to mobility and diet breadth could explain the observed evenness patterns. We found a clear negative effect of area and a weaker, but positive effect of connectivity on evenness. Communities in small habitat fragments were mainly composed of mobile and generalist species. The higher evenness in small fragments could thereby be generated by highly mobile species that maintain local populations with frequent inter-fragment movements. Trait analysis suggested an increasing importance of dispersal over local recruitment, as we move from large to small fragments and from less to more connected fragments. Species richness and evenness were negatively correlated indicating that the two variables responded differently to habitat area and connectivity, although the mechanisms underlying the observed patterns are difficult to isolate. Even though habitat area and connectivity often decrease simultaneously due to habitat fragmentation, an interesting practical implication of the contrasting effect of the two variables is that the resulting community composition will depend on the relative strength of these two processes

The lung microbiota in early rheumatoid arthritis and autoimmunity

BACKGROUND: Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. This suggests the possibility that the lung could be a site of autoimmunity generation in RA, perhaps in response to microbiota changes. We therefore sought to test whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity. METHODS: 16S rRNA gene high-throughput sequencing was utilized to compare the bacterial community composition of bronchoalveolar lavage fluid (BAL) in patients with early, disease-modifying anti-rheumatic drugs (DMARD)-naive RA, patients with lung sarcoidosis, and healthy control subjects. Samples were further assessed for the presence and levels of anti-citrullinated peptide antibodies (including fine specificities) in both BAL and serum. RESULTS: The BAL microbiota of RA patients was significantly less diverse and abundant when compared to healthy controls, but similar to sarcoidosis patients. This distal airway dysbiosis was attributed to the reduced presence of several genus (i.e., Actynomyces and Burkhordelia) as well as reported periodontopathic taxa, including Treponema, Prevotella, and Porphyromonas. While multiple clades correlated with local and systemic levels of autoantibodies, the genus Pseudonocardia and various related OTUs were the only taxa overrepresented in RA BAL and correlated with higher disease activity and erosions. CONCLUSIONS: Distal airway dysbiosis is present in untreated early RA and similar to that detected in sarcoidosis lung inflammation. This community perturbation, which correlates with local and systemic autoimmune/inflammatory changes, may potentially drive initiation of RA in a proportion of cases