Evaluation of methods of detecting cell reactive oxygen species production for drug screening and cell cycle studies

Intracellular reactive oxygen species (ROS) production is essential to normal cell function. However, excessive ROS production causes oxidative damage and cell death. Many pharmacological compounds exert their effects on cell cycle progression by changing intracellular redox state and in many cases cause oxidative damage leading to drug cytotoxicity. Appropriate measurement of intracellular ROS levels during cell cycle progression is therefore crucial in understanding redox-regulation of cell function and drug toxicity and for the development of new drugs. However, due to the extremely short half-life of ROS, measuring the changes in intracellular ROS levels during a particular phase of cell cycle for drug intervention can be challenging. In this article, we have provided updated information on the rationale, the applications, the advantages and limitations of common methods for screening drug effects on intracellular ROS production linked to cell cycle study. Our aim is to facilitate biomedical scientists and researchers in the pharmaceutical industry in choosing or developing specific experimental regimens to suit their research needs.

Modulation of potassium channels inhibits bunyavirus infection

Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K+) channels to infect cells. Time of addition assays using K+ channel modulating agents demonstrated that K+ channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K+ channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, twin-pore domain K+ channels (K2P) were identified as the K+ channel family mediating BUNV K+ channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease.

Elderly learners and Massive Open Online Courses: a review

Background: Massive open online courses (MOOCs) have become commonplace in the e-learning landscape. Thousands of elderly learners are participating in courses offered by various institutions on a multitude of platforms in many different languages. However, there is very little research into understanding elderly learners in MOOCs. Objective: We aim to show that a considerable proportion of elderly learners are participating in MOOCs and that there is a lack of research in this area. We hope this assertion of the wide gap in research on elderly learners in MOOCs will pave the way for more research in this area. Methods: Pre-course survey data for 10 University of Reading courses on the FutureLearn platform were analyzed to show the level of participation of elderly learners in MOOCs. Two MOOC aggregator sites (Class Central and MOOC List) were consulted to gather data on MOOC offerings that include topics relating to aging. In parallel, a selected set of MOOC platform catalogues, along with a recently published review on health and medicine-related MOOCs, were searched to find courses relating to aging. A systematic literature search was then employed to identify research articles on elderly learners in MOOCs. Results: The 10 courses reviewed had a considerable proportion of elderly learners participating in them. For the over-66 age group, this varied from 0.5% (on the course “Managing people”) to 16.3% (on the course “Our changing climate”), while for the over-56 age group it ranged from 3.0% (on “A beginners guide to writing in English”) to 39.5% (on “Heart health”). Only six MOOCs were found to include topics related to aging: three were on the Coursera platform, two on the FutureLearn platform, and one on the Open2Study platform. Just three scholarly articles relating to MOOCs and elderly learners were retrieved from the literature search. Conclusions: This review presents evidence to suggest that elderly learners are already participating in MOOCs. Despite this, there has been very little research into their engagement with MOOCs. Similarly, there has been little research into exploiting the scope of MOOCs for delivering topics that would be of interest to elderly learners. We believe there is potential to use MOOCs as a way of tackling the issue of loneliness among older adults by engaging them as either resource personnel or learners.

Kinetics analysis and automated online screening of aminocarbonylation of aryl halides in flow

Temperature, pressure, gas stoichiometry, and residence time were varied to control the yield and product distribution of the palladium-catalyzed aminocarbonylation of aromatic bromides in both a silicon microreactor and a packed-bed tubular reactor. Automation of the system set points and product sampling enabled facile and repeatable reaction analysis with minimal operator supervision. It was observed that the reaction was divided into two temperature regimes. An automated system was used to screen steady-state conditions for offline analysis by gas chromatography to fit a reaction rate model. Additionally, a transient temperature ramp method utilizing online infrared analysis was used, leading to more rapid determination of the reaction activation energy of the lower temperature regimes. The entire reaction spanning both regimes was modeled in good agreement with the experimental data.