Datta, S. | bioRxiv Science

bioRxiv2018

Spatio-temporal modelling of Leishmania infantum infection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil

BackgroundThe parasite Leishmania infantum causes zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease.\n\nLeishmania infantum parasites are transmitted between hosts during blood feeding by infected female phlebotomine sand flies. With a principal reservoir host of L. infantum being domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models.\n\nMethodsWe have developed a stochastic, spatial, individual-based mechanistic model of L. infantum transmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fit distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters.\n\nResultsWe computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence of L. infantum infection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected with L. infantum parasites.\n\nConclusionsEstablishing the model parameters with the highest sensitivity of average L. infantum infection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.

epidemiology↗

bioRxiv2018

SciReader*: A Cloud-based Recommender System for Biomedical Literature

With the growing number of biomedical papers published each year, keeping up with relevant literature has become increasingly important, and yet more challenging. SciReader (www.scireader.com) is a cloud-based personalized recommender system that specifically aims to assist biomedical researchers and clinicians identify publications of interest to them. SciReader uses topic modeling and other machine learning algorithms to provide users with recommendations that are recent, relevant, and of high quality1.

scientific communication and education↗

bioRxiv2018

Cholesterol depletion by MβCD enhances membrane tension, its heterogeneity and affects cellular integrity.

Cholesterol depletion in cells by M{beta}CD remodels the plasma membranes mechanics and its interactions with the underlying cytoskeleton. Decoupling the two effects and studying various alterations to the membranes mechanical parameters is important for understanding cholesterols role in cellular response to stress. By mapping membrane height fluctuations in single cells, we report that M{beta}CD treatment reduces temporal fluctuations and flattens out the membrane - but does not supress activity-driven fluctuations. We find that membrane tension increase contributes most to the altered fluctuations, among the multiple mechanical parameters computed. Maps also reveal an enhanced long-range heterogeneity within single cells, both in amplitude of fluctuations and membrane tension on cholesterol depletion. To check if this alters the tenacity of membrane to mechanical stress we use hypo-osmotic shock. We find that on M{beta}CD treatment, cells are more prone to rupture than control cells, and this is not hindered by actomyosin perturbations. We report increased rupture sizes on cholesterol depletion and argue that, together, this indicates decreased lysis and line tension. Therefore, we show that cholesterol depletion directly affects cell membranes not only by enhancing membrane-cytoskeleton interactions, but also by increasing membrane tension while reducing lysis tension - hence making cells prone to rupture.

biophysics↗