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Ventura, G.

Publications and source records attributed to Ventura, G..

4 recordsLinked to original sources

StressNET: an adaptable deep-learning model for mechanical stress inference in tissues

Mechanical interactions between cells are fundamental to tissue morphogenesis during development and regeneration. Computational methods that infer intercellular stresses from microscopy images of cell shapes offer a non-invasive alternative to experimental perturbation techniques, yet all existing approaches rely on explicit physical models. Here we present StressNET, a Graph Neural Network (GNN) that infers intercellular mechanical stresses directly from tissue geometry, without assuming any underlying physical model. We generated synthetic datasets to train and benchmark StressNET, and demonstrate that its predictions achieve state-of-the-art correlation with experimental stress proxies in zebrafish neuromasts and Xenopus embryos. Analysis of the network's latent space reveals that StressNET learns global organizational principles of mechanical stress distribution, beyond local cell-cell interactions. StressNET is open-source and provides pre-trained models that can be fine-tuned on in vivo data, making it a broadly adaptable tool for studying tissue mechanics across biological systems.

bioinformatics↗

ForSys: non-invasive stress inference from time-lapse microscopy

During tissue development and regeneration, cells interpret and exert mechanical forces that are challenging to measure in vivo. Therefore, stress inference algorithms have emerged as powerful tools to estimate tissue stresses. However, how to incorporate tissue dynamics effectively into the inference remains elusive. Here, we present ForSys, a Python-based software that estimates intercellular stresses and intracellular pressures using time-lapse microscopy. We validated ForSys in silico and in vivo using the well-characterized mucociliary epithelium of the Xenopus embryo. We applied ForSys to study the migrating zebrafish lateral line primordium. We found that stress increases during cell rounding just before cell division and predicted the onset of epithelial rosettogenesis with high accuracy. Finally, we analyzed the development of the zebrafish neuromast and inferred mechanical asymmetries in a cell type-specific adhesion pattern. The versatility and simplicity of ForSys enhance the toolkit for studying spatiotemporal patterns of mechanical forces during tissue morphogenesis in vivo.

systems biology↗

The need to harmonize insecticide resistance testing: methodology, intensity concentrations and molecular mechanisms evaluated in Aedes aegypti populations in Central America and Hispaniola

BackgroundThe Zika AIRS Project, a USAID-funded initiative worked across the Latin America and Caribbean regions from 2016 to 2019, as an emergency to contain the spread of the Zika virus. All entomological records in the target countries showed wide distribution and high abundance of Aedes aegypti populations, however the susceptibility profiles of these insects to insecticides commonly employed by vector control campaigns were in most cases incomplete or inexistent. In close collaboration with the Ministries of Health of individual countries, Zika-AIRS teams conducted insecticide susceptibility testing of an array of insecticides in A. aegypti populations of each country. Procedures applied met the standard international protocols instructed by the World Health Organization and Centers for Disease Control and Prevention. Methodology and main findingsThe insecticides tested were selected under categories such as pyrethroids, organophosphates and carbamate. Results showed A. aegypti populations displaying high and widely distributed resistance to all pyrethroids across countries, tolerance to organophosphates and full susceptibility to a carbamate. Key inconsistencies between testing methods are presented and discussed. Additionally, four kdr mutations were analyzed to detect molecular mechanisms of insecticide resistance. The screening for kdr mutations suggested the widespread nature of V1016I mutation, linked to pyrethroid resistance in A. aegypti populations distributed and sampled in the above mentioned regions. Conclusions and perspectivesThis multi-country study contributes with updated information to the public health decision-makers across Central America and the Caribbean. This study provided training and established technical networks for more effective and sustainable insecticide surveillance programs. Most but not all records of insecticide resistance in A. aegypti were consistent between methodologies, thus inconsistent issues are discussed here to call for further improvement in procedures and convey more practical guidelines for surveillance teams in countries where Aedes-borne diseases are endemic. Author summaryAt the forefront of the fight against arboviruses transmission is the insecticide-based vector control. All countries in the Latin American and Caribbean region invest valuable resources from their limited budget to acquire and implement insecticide-based tools, with non-existent or weak insecticide resistance monitoring programs. Hence, the USAID-funded Zika AIRS Project (ZAP) collaborated with the Ministries of Health of multiple countries to update the profile of susceptibility to insecticides in Aedes aegypti populations. We found widespread resistance to pyrethroid and organophosphate insecticides, which account to almost 100% of the products available to control adult mosquitoes. As we used both of World Health Organization and Centers for Disease Control and Prevention standard methods, we found many similarities and some inconsistencies in the susceptibility profiles obtained for the very same vector populations. Additionally, we obtained insight on potential molecular mechanisms of resistance across the countries, finding the kdr mutation V1016I possibly involved in loss of susceptibility. This study is the biggest cross-country update of insecticide resistance for Aedes aegypti in years, and it should be used as evidence for improving the selection of insecticides in these countries and a call for further support to maintain insecticide resistance monitoring programs.

ecology↗

Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC

Apical-basal polarity underpins the formation of specialized epithelial barriers that are critical for metazoan physiology. Although apical-basal polarity is long known to require the basolateral determinants Lethal Giant Larvae (Lgl), Discs Large (Dlg) and Scribble (Scrib), mechanistic understanding of their function is limited. Lgl plays a role as an aPKC inhibitor, but it remains unclear whether Lgl also forms a complex with Dlg or Scrib. Using fluorescence recovery after photobleaching, we show that Lgl does not form immobile complexes at the lateral domain of Drosophila follicle cells. Optogenetic depletion of plasma membrane phosphatidylinositol 4,5-biphosphate (PIP2) or Dlg removal accelerate Lgl cortical dynamics. However, whereas Lgl turnover relies on PIP2 binding, Dlg and Scrib are only required for Lgl localization and dynamic behavior in the presence of aPKC function. Furthermore, light-induced oligomerization of basolateral proteins indicate that Lgl is not part of the Scrib-Dlg complex in vivo. Thus, Scrib-Dlg are necessary to repress aPKC activity in the lateral domain but do not provide cortical binding sites for Lgl. Our work therefore highlights that Lgl does not act in a complex but in parallel with Scrib-Dlg to antagonize apical determinants.

developmental biology↗