Loss of genetic diversity and increased genetic structuring in response to forest area reduction in a ground dwelling insect: a case study of the flightless carabid beetle Carabus problematicus (Coleoptera, Carabidae)

1.Old growth temperate broadleaved forests are characterised by a large proportion of forest specialists with low dispersal capability. Hence, species bound to this habitat are expected to be highly susceptible to the effects of decreasing patch size and increasing isolation. 2. Here, we investigate the relative effect of both factors by genotyping individuals of a flightless and forest specialist beetle Carabus problematicus from 29 populations, sampled in 21 different forest fragments in Belgium, at eight microsatellite loci. 3. A high degree of genetic differentiation among fragments was observed, with populations from smaller forests being considerably more differentiated and characterised by a lower genetic diversity compared to those of larger forests. 4. A more detailed study on forest remnants of a former historic continuous woodland area revealed that population differentiation was high among, but not within remnants, irrespective of geographical distance. This suggests that patch fragmentation rather than geographical distance is the ultimate factor that hampers gene flow in this species. 5. he results indicate that gene flow among suitable habitat patches is primarily reduced by the inability of this specialised species to traverse the landscape matrix. This lack of dispersal may pose a serious threat for the persistence of C. problematicus and ecologically similar species, and suggests that present populations can best be protected by securing or increasing the size of existing habitat patches

ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids

CD1d-restricted invariant natural killer T (iNKT) cells constitute a common glycolipid-reactive innate-like T-cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d-dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d-dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol-requiring enzyme-1a (IRE1α) and protein kinase R-like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d-restricted iNKT cell responses through induction of distinct classes of neutral lipids

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task