Concomitant Pyroptotic and Apoptotic Cell Death Triggered in Monocytes Infected by Zika Virus

ABSTRACTZika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetus. As a mosquito-borne arbovirus, ZIKV enters bloodstream and is transmitted into the fetus through the placenta in pregnant women. Monocytes are considered one of the earliest blood cell types to be infected by ZIKV. As a first line defence, monocytes are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV carried out a productive infection, which lead to cell death in human and murine monocytic cells. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdemin D (GSDMD) as well as increased secretion of IL-1β and IL-18, suggesting that the inflammasome was activated that may lead to pyroptosis in infected monocytes. The pyroptosis was NLRP3-dependent and could be suppressed in the monocytes treated with shRNA to target and knockdown caspase-1, or an inhibited for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected monocytes, with multiple mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.

Nested sampling for materials

We review the materials science applications of the nested sampling (NS) method, which was originally conceived for calculating the evidence in Bayesian inference. We describe how NS can be adapted to sample the potential energy surface (PES) of atomistic systems, providing a straightforward approximation for the partition function and allowing the evaluation of thermodynamic variables at arbitrary temperatures. After an overview of the basic method, we describe a number of extensions, including using variable cells for constant pressure sampling, the semi-grand-canonical approach for multicomponent systems, parallelizing the algorithm, and visualizing the results. We cover the range of materials applications of NS from the past decade, from exploring the PES of Lennard–Jones clusters to that of multicomponent condensed phase systems. We highlight examples how the information gained via NS promotes the understanding of materials properties through a novel way of visualizing the PES, identifying thermodynamically relevant basins, and calculating the entire pressure–temperature(–composition) phase diagram. Graphic abstract

Efficient facemask decontamination via forced ozone convection

The COVID-19 crisis has taken a significant toll on human life and the global economy since its start in early 2020. Healthcare professionals have been particularly vulnerable because of the unprecedented shortage of Facepiece Respirators (FPRs), which act as fundamental tools to protect the medical staff treating the coronavirus patients. In addition, many FPRs are designed to be disposable single-use devices, creating an issue related to the generation of large quantities of non-biodegradable waste. In this contribution, we describe a plasma-based decontamination technique designed to circumvent the shortages of FPRs and alleviate the environmental problems posed by waste generation. The system utilizes a Dielectric Barrier Discharge (DBD) to generate ozone and feed it through the fibers of the FPRs. The flow-through configuration is different than canonical ozone-based sterilization methods, in which the equipment is placed in a sealed ozone-containing enclosure without any flow through the mask polymer fibers. We demonstrate the rapid decontamination of surgical masks using Escherichia coli (E. coli) and Vesicular Stomatitis Virus (VSV) as model pathogens, with the flow-through configuration providing a drastic reduction in sterilization time compared to the canonical approach. We also demonstrate that there is no deterioration in mask structure or filtration efficiency resulting from sterilization. Finally, we show that this decontamination approach can be implemented using readily available tools, such as a plastic box, a glass tube, few 3D printed components, and the high-voltage power supply from a plasma globe toy. The prototype assembled for this study is portable and affordable, with effectiveness comparable to that of larger and more expensive equipment.

Guidelines towards plausible interpretation of gospel parables

This study is undertaken against the backdrop of the polyvalence of parables and the resultant arbitrary conclusions reached by many interpreters of gospel parables. It is aimed to set guidelines towards plausible interpretations of these parables. It identified some factors that influence the understanding of the parables and thereby formulated principles for guiding the exegete to plausible conclusions. The genre parable was defined and understood to function metaphorically, implying that the true meaning of parables lies outside of their narrated domain (i.e. in a second, distinct domain). Eight principles were formulated to enhance credible parable exegesis and were explained with illustrations from New Testament parables. They included the need to acknowledge the openness of parables, as well as the need to interpret parables within specific gospel contexts. The attention of interpreters was also drawn to five pitfalls when seeking a plausible interpretation of gospel parables. It became clear that only in a holistic combination could these principles enhance the plausible interpretation of the gospel parables, while isolative considerations would most likely mislead the interpreter. In this article it is concluded that, although parables are polyvalent, this does not justify arbitrary interpretations; hence the need for gospel parable interpreters to take seriously the methods and principles that limit multiplicity and enhance plausibility of the parables’ meanings.Contribution: The contribution of this investigation lies in a canonical approach to gospel parables, and to set guidelines for plausible interpretation from such a stance. While it is recognised that earlier forms of parables, albeit in oral or written form, are of interest in historical critical investigations, the current study works with the forms of parables as embedded in specific gospel narratives.

Canonical Quantum Gravity, Constructive QFT, and Renormalisation

The canonical approach to quantum gravity has been put on a firm mathematical foundation in the recent decades. Even the quantum dynamics can be rigorously defined, however, due to the tremendously non-polynomial character of the gravitational interaction, the corresponding Wheeler–DeWitt operator-valued distribution suffers from quantisation ambiguities that need to be fixed. In a very recent series of works, we have employed methods from the constructive quantum field theory in order to address those ambiguities. Constructive QFT trades quantum fields for random variables and measures, thereby phrasing the theory in the language of quantum statistical physics. The connection to the canonical formulation is made via Osterwalder–Schrader reconstruction. It is well known in quantum statistics that the corresponding ambiguities in measures can be fixed using renormalisation. The associated renormalisation flow can thus be used to define a canonical renormalisation programme. The purpose of this article was to review and further develop these ideas and to put them into context with closely related earlier and parallel programmes.