NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration.</p

Drivers of grassland loss in Hungary during the post-socialist transformation (1987–1999)

The increase in the speed of land-cover change experienced worldwide is becoming a growing concern. Major socio-economic transitions, such as the breakdown of socialism in Europe, may lead to particularly high rates of landscape transformations. In this paper we examined the loss of semi-natural grasslands in Hungary between 1987 and 1999. We studied the relationship between 9 potential driving forces and the fate of grasslands using logistic GLMs. Grassland loss was found to be very high (1.31 % per year), which is far higher than either before or after this period. The most influential predictors of grassland loss were environmental and landscape characteristics (soil type, area of remnant grassland patches), and the socio-economic context (distance to paved road, and nearest settlement, human population density). Several processes and relationships can only be understood from a historical perspective (e.g. large extent of afforestation, strong decrease of soil water table). Grassland loss during the study period emerged as a consequence of survival strategies of individual farmers seeking adaptation to the changing environmental and socio-economic conditions, and not urbanization and agricultural intensification which are the main underlying drivers for the ongoing landscape transformations in most parts of the developed world. Though globalization increasingly influences local land use decisions , reconstructing and modelling recent landscape changes cannot be done without a proper understanding of local history and culture. Our analysis shows the importance of large-area yet high resolution landscape change research, which may reveal unexpected patterns of land cover change, undetected at coarser scales

Deterministic programming of human pluripotent stem cells into microglia facilitates studying their role in health and disease.

Microglia, the resident immune cells of the central nervous system (CNS), are derived from yolk-sac macrophages that populate the developing CNS during early embryonic development. Once established, the microglia population is self-maintained throughout life by local proliferation. As a scalable source of microglia-like cells (MGLs), we here present a forward programming protocol for their generation from human pluripotent stem cells (hPSCs). The transient overexpression of PU.1 and C/EBPβ in hPSCs led to a homogenous population of mature microglia within 16 d. MGLs met microglia characteristics on a morphological, transcriptional, and functional level. MGLs facilitated the investigation of a human tauopathy model in cortical neuron-microglia cocultures, revealing a secondary dystrophic microglia phenotype. Single-cell RNA sequencing of microglia integrated into hPSC-derived cortical brain organoids demonstrated a shift of microglia signatures toward a more-developmental in vivo-like phenotype, inducing intercellular interactions promoting neurogenesis and arborization. Taken together, our microglia forward programming platform represents a tool for both reductionist studies in monocultures and complex coculture systems, including 3D brain organoids for the study of cellular interactions in healthy or diseased environments

Cadmium-zinc accumulation and photosystem II responses of Noccaea caerulescens to Cd and Zn exposure

A population of the metallophyte Noccaea (Thlaspi) caerulescens originating from a Zn-enriched area at Roros Copper Mine (Norway) was studied. N. caerulescens tolerance to accumulate Cd and Zn was evaluated in hydroponic experiments by chlorophyll fluorescence imaging analysis. In the field-collected N. caerulescens mother plants, Zn shoot concentrations were above Zn hyperaccumulation threshold while, in hydroponic experiments under 40-mu M Cd exposure, shoot Cd concentrations were clearly above Cd hyperaccumulation threshold. Cadmium ions and, to a less extent, Zn were mainly retained in the roots. Exposure to Cd enhanced Zn translocation to the shoot, while decreased significant total Ca2+ uptake, suggesting that Cd uptake occurs through Ca2+ transporters. Nevertheless, it increased Ca2+ translocation to the leaf, possibly for photoprotection of photosystem II (PSII). Exposure to 800 mu M Zn or 40 mu M Cd resulted in increased Fe3+ uptake suggesting that in N. caerulescens, Cd uptake does not take place through the pathway of Fe3+ uptake and that conditions that lead to Cd and Zn accumulation in plants may also favor Fe accumulation. Despite the significant high toxicity levels of Zn and Cd in leaves, under Zn and Cd exposure, respectively, the allocation of absorbed light energy at PSII did not differ compared to controls. The results showed that N. caerulescens keep Cd and Zn concentrations in the mesophyll cells in non-toxic forms for PSII and that the increased Ca and Fe accumulation in leaves alleviates the toxicity effects. Chlorophyll fluorescence imaging revealed that PSII of N. caerulescens resisted better the phytotoxic effects of 20 times higher Zn than Cd exposure concentration. Overall, it is concluded that the use of chlorophyll fluorescence imaging constitutes a promising basis for investigating heavy metal tolerance of plants