Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease

Background Little is known about the roles of myeloid cell subsets in kidney injury and in the limited ability of the organ to repair itself. Characterizing these cells based only on surface markers using flow cytometry might not provide a full phenotypic picture. Defining these cells at the single-cell, transcriptomic level could reveal myeloid heterogeneity in the progression and regression of kidney disease. Methods Integrated droplet– and plate-based single-cell RNA sequencing were used in the murine, reversible, unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single-cell level during renal injury and the resolution of fibrosis. Paired blood exchange tracked the fate of monocytes recruited to the injured kidney. Results A single-cell atlas of the kidney generated using transcriptomics revealed marked changes in the proportion and gene expression of renal cell types during injury and repair. Conventional flow cytometry markers would not have identified the 12 myeloid cell subsets. Monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1, before transitioning to become Ccr21 macrophages that accumulate in late injury. Conversely, a novel Mmp121 macrophage subset acts during repair. Conclusions Complementary technologies identified novel myeloid subtypes, based on transcriptomics in single cells, that represent therapeutic targets to inhibit progression or promote regression of kidney disease

TCR-stimulated changes in cell surface CD46 expression generate type 1 regulatory T cells

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Might Depression, Psychosocial Adversity, and Limited Social Assets Explain Vulnerability to and Resistance against Violent Radicalisation?

BACKGROUND: This study tests whether depression, psychosocial adversity, and limited social assets offer protection or suggest vulnerability to the process of radicalisation. METHODS: A population sample of 608 men and women of Pakistani or Bangladeshi origin, of Muslim heritage, and aged 18-45 were recruited by quota sampling. Radicalisation was measured by 16 questions asking about sympathies for violent protest and terrorism. Cluster analysis of the 16 items generated three groups: most sympathetic (or most vulnerable), most condemning (most resistant), and a large intermediary group that acted as a reference group. Associations were calculated with depression (PHQ9), anxiety (GAD7), poor health, and psychosocial adversity (adverse life events, perceived discrimination, unemployment). We also investigated protective factors such as the number social contacts, social capital (trust, satisfaction, feeling safe), political engagement and religiosity. RESULTS: Those showing the most sympathy for violent protest and terrorism were more likely to report depression (PHQ9 score of 5 or more; RR = 5.43, 1.35 to 21.84) and to report religion to be important (less often said religion was fairly rather than very important; RR = 0.08, 0.01 to 0.48). Resistance to radicalisation measured by condemnation of violent protest and terrorism was associated with larger number of social contacts (per contact: RR = 1.52, 1.26 to 1.83), less social capital (RR = 0.63, 0.50 to 0.80), unavailability for work due to housekeeping or disability (RR = 8.81, 1.06 to 37.46), and not being born in the UK (RR = 0.22, 0.08 to 0.65). CONCLUSIONS: Vulnerability to radicalisation is characterised by depression but resistance to radicalisation shows a different profile of health and psychosocial variables. The paradoxical role of social capital warrants further investigation

Size constancy is preserved but afterimages are prolonged in typical individuals with higher degrees of self-reported autistic traits

Deficits in perceptual constancies from early infancy have been proposed to contribute to autism and exacerbate its symptoms (Hellendoorn et al., Frontiers in Psychology 6:1–16, 2015). Here, we examined size constancy in adults from the general population (N = 106) with different levels of self-reported autistic traits using an approach based on negative afterimages. The afterimage strength, as indexed by duration and vividness, was also quantified. In opposition to the Hellendoorn and colleagues’ model, we were unable to demonstrate any kind of relationship between abilities in size constancy and autistic traits. However, our results demonstrated that individuals with higher degrees of autistic traits experienced more persistent afterimages. We discuss possible retinal and post-retinal explanations for prolonged afterimages in people with higher levels of autistic traits

Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL

Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin

Evaluation of the performance of coated and uncoated carbide tools in drilling thick CFRP/aluminium alloy stacks

This paper aims to establish the wear mechanisms of coated and uncoated tungsten carbide drills when drilling carbon fibre reinforced plastics (CFRP)/aluminium alloy (Al) stacks. During the drilling experiments, thrust forces were measured. A scanning electron microscope (SEM) and a numerical microscope, provided with a scanning device, were periodically used to analyse tool wear mechanisms and to measure wear progression of the tool cutting edges. For both coated and uncoated drills, abrasion was the dominant tool wear mechanism, affecting the entire cutting edges. Higher wear was observed on uncoated tools which caused a significant increase in thrust force during drilling both Al and CFRP materials. The influence of these phenomena on the quality of the holes and on the generated roughness was also discussed.FUI-Usinage de Multi-Matériaux et Innovation (U2MI