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The cytotoxicity of cadmium (Cd), arsenate (As(V)), and arsenite (As(III)) on a strain of Chlamydomonas acidophila, isolated from the Rio Tinto, an acidic environment containing high metal(l)oid concentrations, was analyzed. We used a broad array of methods to produce complementary information cell viability and reactive oxygen species (ROS) generation measures, ultrastructural observations, transmission electron microscopy energy dispersive x-ray microanalysis (TEM-XEDS), and gene expression. This acidophilic microorganism was affected differently by the tested metal/metalloid It showed high resistance to arsenic while Cd was the most toxic heavy metal, showing an LC50 = 1.94 µM. Arsenite was almost four-fold more toxic (LC50= 10.91 mM) than arsenate (LC50 = 41.63 mM). Assessment of ROS generation indicated that both arsenic oxidation states generate superoxide anions. Ultrastructural analysis of exposed cells revealed that stigma, chloroplast, nucleus, and mitochondria were the main toxicity targets. Intense vacuolization and accumulation of energy reserves (starch deposits and lipid droplets) were observed after treatments. Electron-dense intracellular nanoparticle-like formation appeared in two cellular locations inside cytoplasmic vacuoles and entrapped into the capsule, around each cell. The chemical nature (Cd or As) of these intracellular deposits was confirmed by TEM-XEDS. Additionally, they also contained an unexpected high content in phosphorous, which might support an essential role of poly-phosphates in metal resistance.To deal with drawbacks of paper-based data collection procedures, the QuestionSys approach empowers researchers with none or little programming knowledge to flexibly configure mobile data collection applications on demand. The mobile application approach of QuestionSys mainly pursues the goal to mitigate existing drawbacks of paper-based collection procedures in mHealth scenarios. Importantly, researchers shall be enabled to gather data in an efficient way. To evaluate the applicability of QuestionSys, several studies have been carried out to measure the efforts when using the framework in practice. In this work, the results of a study that investigated psychological insights on the required mental effort to configure the mobile applications are presented. Specifically, the mental effort for creating data collection instruments is validated in a study with N = 80 participants across two sessions. Thereby, participants were categorized into novices and experts based on prior knowledge on process modeling, which is a fundamental pillar of the developed approach. Each participant modeled 10 instruments during the course of the study, while concurrently several performance measures are assessed (e.g., time needed or errors). The results of these measures are then compared to the self-reported mental effort with respect to the tasks that had to be modeled. On one hand, the obtained results reveal a strong correlation between mental effort and performance measures. On the other, the self-reported mental effort decreased significantly over the course of the study, and therefore had a positive impact on measured performance metrics. Altogether, this study indicates that novices with no prior knowledge gain enough experience over the short amount of time to successfully model data collection instruments on their own. Therefore, QuestionSys is a helpful instrument to properly deal with large-scale data collection scenarios like clinical trials.The advent of Internet of Things (IoT) brought innovation along with unprecedented benefits of convenience and efficacy in many operations that were otherwise very cumbersome. This innovation explosion has surfaced a new dimension of vulnerability and physical threat to the data integrity of IoT networks. Implementing conventional cryptographic algorithms on IoT devices is not future-proof as these devices are constrained in terms of computational power, performance, and memory. In this paper, we are proposing a novel framework, a unique model that integrates IoT networks with a blockchain to address potential privacy and security threats for data integrity. Smart contracts are instrumental in this integration process and they are used to handle device authentication, authorization and access-control, and data management. G Protein inhibitor We further share a new design model for interfaces to integrate both platforms while highlighting its performance results over the existing models. With the incorporation of off-chain data storage into the framework, overall scalability of the system can be increased. Finally, our research concludes how the proposed framework can be fused virtually into any existing IoT applications with minimal modifications.Genetic defects of human galactose-1-phosphate uridyltransferase (hGALT) and the partial loss of enzyme function result in an altered galactose metabolism with serious long-term developmental impairment of organs in classic galactosemia patients. In search for cellular pathomechanisms induced by the stressor galactose, we looked for ways to induce metabolically a galactosemia-like phenotype by hGALT inhibition in HEK293 cells. In kinetic studies, we provide evidence for 2-fluorinated galactose-1-phosphate (F-Gal-1-P) to competitively inhibit recombinant hGALT with a KI of 0.9 mM. Contrasting with hepatic cells, no alterations of N-glycoprofiles in MIG (metabolic induction of galactosemia)-HEK293 cells were revealed for an inducible secretory netrin-1 probe by MALDI-MS. Differential fluorescence-activated cell sorting demonstrated reduced surface expression of N-glycosylated CD109, EGFR, DPP4, and rhMUC1. Membrane raft proteomes exhibited dramatic alterations pointing to an affection of the unfolded protein response, and of targeted protein traffick. Most prominent, a negative regulation of oxidative stress was revealed presumably as a response to a NADPH pool depletion during reduction of Gal/F-Gal. Cellular perturbations induced by fluorinated galactoses in normal epithelial cells resemble proteomic changes revealed for galactosemic fibroblasts. In conclusion, the metabolic induction of galactosemia-like phenotypes in healthy epithelial/neuronal cells could support studies on the molecular pathomechanisms in classic galactosemia, in particular under conditions of low galactose stress and residual GALT activity.

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