Toxicological effects of long-term continuous exposure to ambient air on human bronchial epithelial Calu-3 cells exposed at the air-liquid interface.

Air pollution significantly contributes to the global burden of respiratory and cardiovascular diseases. While single source/compound studies dominate current research, long-term, multi-pollutant studies are crucial to understanding the health impacts of environmental aerosols. Our study aimed to use the first air-liquid interface (ALI) aerosol exposure system adapted for long-term in vitro exposures for ambient air in vitro exposure.

Comparing the Toxicological Responses of Pulmonary Air-Liquid Interface Models upon Exposure to Differentially Treated Carbon Fibers.

In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air-liquid interface cell culture models of the human lung to CF.

U-to-C RNA editing by synthetic PPR-DYW proteins in bacteria and human culture cells.

Programmable RNA editing offers significant therapeutic potential for a wide range of genetic diseases. Currently, several deaminase enzymes, including ADAR and APOBEC, can perform programmable adenosine-to-inosine or cytidine-to-uridine RNA correction. However, enzymes to perform guanosine-to-adenosine and uridine-to-cytidine (U-to-C) editing are still lacking to complete the set of transition reactions.

Cofactor-independent RNA editing by a synthetic S-type PPR protein.

Pentatricopeptide repeat (PPR) proteins are RNA-binding proteins that are attractive tools for RNA processing in synthetic biology applications given their modular structure and ease of design. Several distinct types of motifs have been described from natural PPR proteins, but almost all work so far with synthetic PPR proteins has focused on the most widespread P-type motifs. We have investigated synthetic PPR proteins based on tandem repeats of the more compact S-type PPR motif found in plant organellar RNA editing factors and particularly prevalent in the lycophyte .

Analysis of a gene family for PDF-like peptides from Arabidopsis.

Plant defensins are small, basic peptides that have a characteristic three-dimensional folding pattern which is stabilized by four disulfide bridges. We show here that Arabidopsis contains in addition to the proper plant defensins a group of 9 plant defensin-like (PdfL) genes. They are all expressed at low levels while GUS fusions of the promoters showed expression in most tissues with only minor differences.

A synthetic RNA editing factor edits its target site in chloroplasts and bacteria.

Members of the pentatricopeptide repeat (PPR) protein family act as specificity factors in C-to-U RNA editing. The expansion of the PPR superfamily in plants provides the sequence variation required for design of consensus-based RNA-binding proteins. We used this approach to design a synthetic RNA editing factor to target one of the sites in the Arabidopsis chloroplast transcriptome recognised by the natural editing factor CHLOROPLAST BIOGENESIS 19 (CLB19).

The Pentatricopeptide Repeat Protein MEF100 Is Required for the Editing of Four Mitochondrial Editing Sites in .

In there are more than 600 C-to-U RNA editing events in the mitochondria and at least 44 in the chloroplasts. Pentatricopeptide repeat (PPR) proteins provide the specificity for these reactions. They recognize RNA sequences in a partially predictable fashion via key amino acids at the fifth and last position in each PPR motif that bind to individual ribonucleotides.

The Concept of Chemical Generators: On-Site On-Demand Production of Hazardous Reagents in Continuous Flow.

In recent years, a steadily growing number of chemists, from both academia and industry, have dedicated their research to the development of continuous flow processes performed in milli- or microreactors. The common availability of continuous flow equipment at virtually all scales and affordable cost has additionally impacted this trend. Furthermore, regulatory agencies such as the United States Food and Drug Administration actively encourage continuous manufacturing of active pharmaceutical ingredients (APIs) with the vision of quality and productivity improvements.

The Expansion and Diversification of Pentatricopeptide Repeat RNA-Editing Factors in Plants.

The RNA-binding pentatricopeptide repeat (PPR) family comprises hundreds to thousands of genes in most plants, but only a few dozen in algae, indicating massive gene expansions during land plant evolution. The nature and timing of these expansions has not been well defined due to the sparse sequence data available from early-diverging land plant lineages. In this study, we exploit the comprehensive OneKP datasets of over 1000 transcriptomes from diverse plants and algae toward establishing a clear picture of the evolution of this massive gene family, focusing on the proteins typically associated with RNA editing, which show the most spectacular variation in numbers and domain composition across the plant kingdom.

Continuous-Flow Pd-Catalyzed Carbonylation of Aryl Chlorides with Carbon Monoxide at Elevated Temperature and Pressure.

The development of a continuous-flow protocol for a palladium-catalyzed methoxycarbonylation of (hetero)aryl chlorides using carbon monoxide gas and methanol is described. (Hetero)aryl chlorides are the least expensive of the aryl halides, but are underutilized in carbonylation reactions due to their very poor reactivity. The described protocol exploits intensified conditions at elevated temperature and pressure, which are readily accessed within a continuous-flow environment, to provide moderate to excellent product yields (11 examples) in a short 16 min residence time.

Towards a plant model for enigmatic U-to-C RNA editing: the organelle genomes, transcriptomes, editomes and candidate RNA editing factors in the hornwort Anthoceros agrestis.

Hornworts are crucial to understand the phylogeny of early land plants. The emergence of 'reverse' U-to-C RNA editing accompanying the widespread C-to-U RNA editing in plant chloroplasts and mitochondria may be a molecular synapomorphy of a hornwort-tracheophyte clade. C-to-U RNA editing is well understood after identification of many editing factors in models like Arabidopsis thaliana and Physcomitrella patens, but there is no plant model yet to investigate U-to-C RNA editing.

The E domain of CRR2 participates in sequence-specific recognition of RNA in plastids.

Pentatricopeptide repeat (PPR) proteins are modular RNA-binding proteins involved in different aspects of RNA metabolism in organelles. PPR proteins of the PLS subclass often contain C-terminal domains that are important for their function, but the role of one of these domains, the E domain, is far from resolved. Here, we elucidate the role of the E domain in CRR2 in plastids.

Effects of Endurance Exercise Bouts in Hypoxia, Hyperoxia, and Normoxia on mTOR-Related Protein Signaling in Human Skeletal Muscle.

Przyklenk, A, Aussieker, T, Gutmann, B, Schiffer, T, Brinkmann, C, Strüder, HK, Bloch, W, Mierau, A, and Gehlert, S. Effects of endurance exercise bouts in hypoxia, hyperoxia, and normoxia on mTOR-related protein signaling in human skeletal muscle. J Strength Cond Res 34(8): 2276-2284, 2020-This study investigated the effects of short-term hypoxia (HY), hyperoxia (PER), and normoxia on anabolic signaling proteins in response to an acute bout of moderate endurance exercise (EEX) before and after an endurance exercise training intervention.

Editing of Chloroplast by PPR Editing Factor EMB2261 Is Essential for Development.

RNA editing in plastids is known to be required for embryogenesis, but no single editing event had been shown to be essential. We show that the mutation is lethal through a failure to express an editing factor that specifically recognizes the site. EMB2261 was predicted to bind the -element upstream of the site and genetic complementation with promoters of different strength followed by RNA-seq analysis was conducted to test the correlation between editing and expression.

The effects of exercise intensity and post-exercise recovery time on cortical activation as revealed by EEG alpha peak frequency.

Acute physical exercise (APE) induces an increase in the individual alpha peak frequency (iAPF), a cortical parameter associated with neural information processing speed. The aim of this study was to further scrutinize the influence of different APE intensities on post-exercise iAPF as well as its time course after exercise cessation. 95 healthy young (18-35 years) subjects participated in two randomized controlled experiments (EX1 and EX2).

Exercise-induced changes in EEG alpha power depend on frequency band definition mode.

In the majority of studies investigating cortical alpha oscillations the alpha frequency is defined as a fixed band thus, neglecting recommendations in the EEG literature to adjust the alpha band according to the individual alpha peak frequency (iAPF). Based on our previous findings indicating exhaustive exercise induces an increase of the post-exercise iAPF, we scrutinized the influence of exercise on post-exercise alpha power by comparing fixed and iAPF-adjusted alpha frequency bands. Resting EEG was recorded from 13 scalp locations in nine subjects before, immediately after as well as ten minutes following an exhaustive exercise protocol on a cycle ergometer.

Endurance Exercise in Hypoxia, Hyperoxia and Normoxia: Mitochondrial and Global Adaptations.

We hypothesized short-term endurance exercise (EN) in hypoxia (HY) to exert decreased mitochondrial adaptation, peak oxygen consumption (VO) and peak power output (PPO) compared to EN in normoxia (NOR) and hyperoxia (PER). 11 male subjects performed repeated unipedal cycling EN in HY, PER, and NOR over 4 weeks in a cross-over design. VO, PPO, rate of perceived exertion (RPE) and blood lactate (Bla) were determined pre- and post-intervention to assess physiological demands and adaptation.

Continuous Flow Homolytic Aromatic Substitution with Electrophilic Radicals: A Fast and Scalable Protocol for Trifluoromethylation.

We report an operationally simple and rapid continuous flow radical C-C bond formation under Minisci-type reaction conditions. The transformations are performed at or below room temperature employing hydrogen peroxide (H O ) and dimethylsulfoxide (DMSO) as reagents in the presence of an Fe catalyst. For electron-rich aromatic and heteroaromatic substrates, C-C bond formation proceeds satisfactorily with electrophilic radicals including CF , C F , CH CN, and CH CO Et.

Breaking Through the Economic Barriers of Anesthesia Information Management Systems.

Anesthesia information management systems (AIMS) are being increasingly used to assist the delivery and documentation of anesthesia services in the United States. The major benefits of AIMS cited in the literature are the ability to (1) reduce costs, (2) facilitate quality assurance and quality improvement processes, (3) increase the accuracy and completeness of the anesthesia record, and (4) improve adherence to recommended guidelines. The major drawback, especially for rural hospitals, is the cost.

Continuous-Flow Electrophilic Amination of Arenes and Schmidt Reaction of Carboxylic Acids Utilizing the Superacidic Trimethylsilyl Azide/Triflic Acid Reagent System.

A continuous flow protocol for the direct stoichiometric electrophilic amination of aromatic hydrocarbons and the Schmidt reaction of aromatic carboxylic acids using the superacidic trimethylsilyl azide/triflic acid system is described. Optimization of reagent stoichiometry, solvent, reaction time, and temperature led to an intensified protocol at elevated temperatures that allows the direct amination of arenes to be completed within 3 min at 90 °C. In order to improve the selectivity and scope of this direct amination protocol, aromatic carboxylic acids were additionally chosen as substrates.

Laboratory-Scale Membrane Reactor for the Generation of Anhydrous Diazomethane.

A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF-2400 tubing and subsequently selectively separated from the tubing into a solvent- and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor-intensive purification operations or exposure of the operator to CH2N2.

Batch- and Continuous-Flow Aerobic Oxidation of 14-Hydroxy Opioids to 1,3-Oxazolidines-A Concise Synthesis of Noroxymorphone.

14-Hydroxymorphinone is converted to noroxymorphone, the immediate precursor of important opioid antagonists, such as naltrexone and naloxone, in a three-step reaction sequence. The initial oxidation of the N-methyl group in 14-hydroxymorphinone with in situ generated colloidal palladium(0) as the catalyst and molecular oxygen as the terminal oxidant constitutes the key transformation in this new route. This oxidation results in the formation of an unexpected oxazolidine ring structure.