Biology subjects

Conrad, J.

Publications and source records attributed to Conrad, J..

2 recordsLinked to original sources

bioRxiv2020

Assessment of ethanol-induced toxicity on iPSC-derived human dopaminergic neurons using a novel high-throughput mitochondrial neuronal health (MNH) assay

Excessive ethanol exposure can cause mitochondrial and cellular toxicity. In order to discover potential counteracting interventions, it is essential to develop assays capable of capturing the consequences of ethanol exposure in human dopaminergic (DA) neurons, which are crucial for the development and maintenance of alcohol use disorders (AUD). Here, we developed a novel high-throughput (HT) assay to quantify mitochondrial and neuronal toxicity in human DA neurons from induced pluripotent stem cells (iPSCs). The assay, dubbed mitochondrial neuronal health (MNH) assay, combines live-cell measurement of mitochondrial membrane potential (MMP) with quantification of neuronal branching complexity post-fixation. Using the MNH assay, we demonstrated that chronic ethanol exposure in human iPSC-derived DA neurons decreases MMP and branching complexity in a dose-dependent manner. The toxic effect of ethanol on DA neurons was already detectable after 1 hour of exposure, and occurred similarly in DA neurons derived from healthy individuals and from patients with AUD. We next used the MNH assay to carry out a proof-of-concept compound screening using FDA-approved drugs. We identified potential candidate drugs modulating acute ethanol toxicity in human DA neurons. Among these drugs, flavoxate and disulfiram influenced mitochondrial neuronal health independently from ethanol, leading to amelioration and worsening, respectively. Altogether, we developed an HT assay to probe human mitochondrial neuronal health and used it to assess ethanol neurotoxicity and to identify modulating agents. The MNH assay represents an effective new tool for discovering modulators of mitochondrial neuronal health and toxicity in live human neurons.

cell biology↗

bioRxiv2020

Silica particles trigger the production of exopolysaccharides in harsh environment plant growth-promoting rhizobacteria and increase their ability to enhance drought tolerance

In coming decades drought is expected to expand globally owing to increased evaporation and reduced rainfall. In order to reduce the vulnerability of agricultural systems we need to understand the crop plant growth environment. Understanding, predicting and controlling the rhizosphere has potential to harness plant microbe interactions, improve plant responses to environmental stress and mitigate effects of climate change. Our plant growth-promoting rhizobacteria (PGPR) are isolated from the natural laboratory Evolution Canyon Israel (EC). The endophytic rhizobacteria from the wild progenitors of cereals have been co-habituated with their hosts for long periods of time. The study revealed that silica particles (SN) triggered the PGPR production of exopolysaccharides (EPS) containing D-glucuronate (D-GA). This leads to increased plant biomass accumulation in drought-stressed growth environments. The PGPR increased EPS content increases the water holding capacity (WHC) and osmotic pressure of the biofilm matrix. Light- and electron-microscopic studies show that in the presence of SN particles, bacterial morphology is changed, indicating that SNs are associated with significant reprogramming in bacteria. The results here show that the production of EPS containing D-GA is induced by SN treatment. The findings encourage formulation of cells considering microencapsulation with materials that ensure higher WHC and hyperosmolarity under field conditions. Our results illustrate the importance of considering natural soil nanoparticles in the application of PGPR. Osmotic pressure involvement of holobiont cohabitation is discussed.

microbiology↗