Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells.

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs initiate C-C motif chemokine receptor 7 (CCR7) expression and migrate into lymph nodes to direct T cell activation and differentiation. The mechanistic underpinnings of DC migration from the tissues to lymph nodes have been largely elucidated, contributing greatly to our understanding of DC functionality and intestinal immunity. In contrast, the molecular mechanisms allowing DCs to efficiently migrate through the complex extracellular matrix of the intestinal lamina propria prior to antigen encounter are still incompletely understood. Here we show that small intestinal murine CD11b <sup>+</sup> CD103 <sup>+</sup> DCs express Placenta-expressed transcript 1 (Plet1), a glycophoshatidylinositol (GPI)-anchored surface protein involved in migration of keratinocytes during wound healing. In the absence of Plet1, CD11b <sup>+</sup> CD103 <sup>+</sup> DCs display aberrant migratory behavior, and accumulate in the small intestine, independent of CCR7 responsiveness. RNA-sequencing indicated involvement of Plet1 in extracellular matrix-interactiveness, and subsequent in-vitro migration assays revealed that Plet1 augments the ability of DCs to migrate through extracellular matrix containing environments. In conclusion, our findings reveal that expression of Plet1 facilitates homeostatic interstitial migration of small intestinal DCs

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.</p

Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs ini

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Can we identify patients with different illness schema following an acute exacerbation of COPD: A cluster analysis

SummaryIntroductionPulmonary Rehabilitation (PR) reduces hospital admissions following an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) but adherence is known to be poor. Patients' illness perceptions may affect adherence to disease-management strategies but to date have not been explored following an exacerbation. The study aim is two-fold; firstly to prospectively explore acceptance and uptake of post-exacerbation PR and secondly to identify possible clusters of patients' illness perceptions following hospitalisation for an exacerbation of COPD.MethodsPatients admitted to hospital with an exacerbation of COPD were recruited to a prospective observational study. Self-reported illness perceptions, mood, health status and self-efficacy were assessed. Acceptance and uptake of PR were recorded at six months. Cluster analysis of Illness Perceptions Questionnaire-Revised data was used to establish groups of patients holding distinct beliefs.Results128 patients were recruited. Acceptance and uptake of PR following an acute exacerbation was poor with only 9% (n = 11) completing the programme. Cluster analysis revealed three distinct groups: Cluster 1 ‘in control’ (n = 52), Cluster 2 ‘disengaged’ (n = 36) and Cluster 3 ‘distressed’ (n = 40). Significant between-cluster differences were observed in mood, health status and self-efficacy (p < 0.01). Acceptance and uptake of PR did not differ between clusters.ConclusionsAcceptance/uptake of post-exacerbation PR was found to be poor. Three distinct illness schema exist in patients following an acute exacerbation. This information may be useful in developing novel psychologically-informed interventions designed to reduce feelings of distress and perhaps facilitate a PR intervention for this vulnerable population