The influence of skeletal muscle anisotropy on electroporation: in vivo study and numerical modeling

The aim of this study was to theoretically and experimentally investigate electroporation of mouse tibialis cranialis and to determine the reversible electroporation threshold values needed for parallel and perpendicular orientation of the applied electric field with respect to the muscle fibers. Our study was based on local electric field calculated with three-dimensional realistic numerical models, that we built, and in vivo visualization of electroporated muscle tissue. We established that electroporation of muscle cells in tissue depends on the orientation of the applied electric field; the local electric field threshold values were determined (pulse parameters: 8 × 100 μs, 1 Hz) to be 80 V/cm and 200 V/cm for parallel and perpendicular orientation, respectively. Our results could be useful electric field parameters in the control of skeletal muscle electroporation, which can be used in treatment planning of electroporation based therapies such as gene therapy, genetic vaccination, and electrochemotherapy

ELIXIR and Toxicology: a community in development [version 2; peer review: 2 approved]

Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology, and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities

Chloroplast redox state changes mark cell-to-cell signaling in the hypersensitive response

Bisphenol A (BPA) is one of the most commonly used substances in the manufacture ofvarious everyday products. Growing concerns about its hazardous properties, including endocrinedisruption and genotoxicity, have led to its gradual replacement by presumably safer analogues inmanufacturing plastics. The widespread use of BPA and, more recently, its analogues has increasedtheir residues in the environment. However, our knowledge of their toxicological profiles is limitedand their combined effects are unknown. In the present study, we investigated the toxic effectscaused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP andBPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed thatBPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP andBPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC)decreased cell viability in a dose-dependent manner, but the significant difference was only observedfor the combination of BPA/BPC (both at 40μM). After 96-h exposure, none of the BPs studiedaffected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cellviability in a dose-dependent manner that was significant for the combination of 4μM BPA and 4μMBPAP. None of the BPs and their binary mixtures studied affected the surface area and growth ofspheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggeredoxidative stress, as measured by the production of reactive oxygen species and malondialdehyde,at both exposure times. Overall, the results suggest that it is important to study the effects of BPsas single compounds. It is even more important to study the effects of combined exposures, as thecombined effects may differ from those induced by single compounds