Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model.

peer reviewedWith Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection, we previously demonstrated that paracrine interferon (IFN)-α2 signalling is required to activate a broad spectrum of interferon-stimulated genes able to counteract a productive VZV infection in hiPSC-neurons. In this new study, we now investigated whether innate immune signalling by VZV-challenged macrophages was able to orchestrate an antiviral immune response in VZV-infected hiPSC-neurons. In order to establish an isogenic hiPSC-neuron/hiPSC-macrophage co-culture model, hiPSC-macrophages were generated and characterised for phenotype, gene expression, cytokine production and phagocytic capacity. Even though immunological competence of hiPSC-macrophages was shown following stimulation with the poly(dA:dT) or treatment with IFN-α2, hiPSC-macrophages in co-culture with VZV-infected hiPSC-neurons were unable to mount an antiviral immune response capable of suppressing a productive neuronal VZV infection. Subsequently, a comprehensive RNA-Seq analysis confirmed the lack of strong immune responsiveness by hiPSC-neurons and hiPSC-macrophages upon, respectively, VZV infection or challenge. This may suggest the need of other cell types, like T-cells or other innate immune cells, to (co-)orchestrate an efficient antiviral immune response against VZV-infected neurons

Improved understanding of regional groundwater drought development through time series modelling: the 2018–2019 drought in the Netherlands

The 2018–2019 drought in north-western and central Europe caused severe damage to a wide range of sectors. It also emphasised the fact that, even in countries with temperate climates, adaptations are needed to cope with increasing future drought frequencies. A crucial component of drought management strategies is to monitor the status of groundwater resources. However, providing up-to-date assessments of regional groundwater drought development remains challenging due to the limited availability of high-quality data. This limits many studies to small selections of groundwater monitoring sites, giving an incomplete image of drought dynamics. In this study, a time series modelling-based method for data preparation was developed and applied to map the spatio-temporal development of the 2018–2019 groundwater drought in the south-eastern Netherlands, based on a large set of monitoring data. The data preparation method was evaluated for its usefulness and reliability for data validation, simulation, and regional groundwater drought assessment. The analysis showed that the 2018–2019 meteorological drought caused extreme groundwater drought throughout the south-eastern Netherlands, breaking 30-year records almost everywhere. Drought onset and duration were strongly variable in space, and higher-elevation areas suffered from severe drought well into 2020. Groundwater drought development appeared to be governed dominantly by the spatial distribution of rainfall and the landscape type. The time series modelling-based data preparation method was found to be a useful tool to enable a spatially detailed record of regional groundwater drought development. The automated time series modelling-based data validation improved the quality and quantity of useable data, although optimal validation parameters are probably context dependent. The time series simulations were generally found to be reliable; however, the use of time series simulations rather than direct measurement series can bias drought estimations, especially at a local scale, and underestimate spatial variability. Further development of time-series-based validation and simulation methods, combined with accessible and consistent monitoring data, will be valuable to enable better groundwater drought monitoring in the future

Hereditary angioedema in 2 sisters due to paternal gonadal mosaicism

We report the occurrence of type I hereditary angioedema in 2 sisters with unaffected parents caused by paternal gonadal mosaicism. Gonadal mosaicism is a rather uncommon genetic phenomenon, but nevertheless, correct diagnosis is important because it may affect further family planning