Allele-Specific Inhibition of Histone Demethylases

Histone demethylases play a critical role in mammalian gene expression by removing methyl groups from lysine residues in degree- and site-specific manner. To specifically interrogate members and isoforms of this class of enzymes, we have developed demethylase variants with an expanded active site. The mutant enzymes are capable of performing lysine demethylation with wild-type proficiency, but are sensitive to inhibition by cofactor-competitive molecules embellished with a complementary steric “bump”. The selected inhibitors show more than 20-fold selectivity over the wild-type demethylase, thus overcoming issues typical to pharmacological and genetic approaches. The mutant–inhibitor pairs are shown to act on a physiologically relevant full-length substrate. By engineering a conserved amino acid to achieve member-specific perturbation, this study provides a general approach for studying histone demethylases in diverse cellular processes.     

Evaluation of the effect of Ultra Rice® EDTA supplementation on the soluble iron,visual acceptance and vitamin A stability of commercial milled rice blends

The addition of NaFeEDTA at only 5% of total iron to ferric pyrophosphate‐fortified Ultra Rice^® increased the in vitro soluble iron ten‐fold. Ultra Rice^® formulated with NaFeEDTA at 2–7% of total iron, or with Na₂EDTA·2H₂O at 0.5× the total iron equivalents, increased the soluble iron seven‐ to thirty‐fold. The colour of the batches was acceptable through 20 weeks at 21 °C, but colour stability needs to be evaluated under authentic storage conditions. Although only 34–46% of the initial vitamin A remained after extrusion, 18‐week storage at 30 °C/70% relative humidity, and simulated cooking, there were indications that losses could be decreased by raising the pH (to ~5) and/or using a better protected vitamin A ingredient. The enhancement of soluble iron afforded by low‐level NaFeEDTA or Na₂EDTA·2H₂O supplementation suggests that this fortification strategy may merit further study as a means of increasing absorbable iron in Ultra Rice^®.     

Homeowner investor subjects as providers of family care and assistance

Abstract

This article asks: What becomes of the idealized asset-accumulating investor subject rallied in asset-based welfare policy and discourse in the context of mounting social risks facing families? It brings into dialogue two disconnected literatures: one on financialized subjectivities, drawing on post-structuralist and Foucauldian analysis, the other on welfare states drawing more heavily on comparative political economy. Drawing on homeowner interviews in Melbourne (Australia), it identifies how parent homeowners’ devise housing strategies to manage their children’s housing welfare risks. Their housing investment and landlordism strategies align with financialized subjectivities, but other strategies subvert or reject these subject positions. Its first contribution is to specify how an Australian refamilization of welfare responsibilities, including for housing, is unfolding as processes of financialization erode the efficacy of growing state social spending. Its second contribution is to challenge the individual subject of asset-based welfare (ABW) and introduce intergenerational assistance as an under-explored contingency for ABW projects, and further driver for welfare inequalities between and within generations.     

Challenges in forming inferences from limited data: a case study of malaria parasite maturation

Inferring biological processes from population dynamics is a common challenge in ecology, particularly when faced with incomplete data. This challenge extends to inferring parasite traits from within-host infection dynamics. We focus on rodent malaria infections (Plasmodium berghei), a system for which previous work inferred an immune-mediated extension in the length of the parasite development cycle within red blood cells. By developing a system of delay-differential equations to describe within-host infection dynamics and simulating data, we demonstrate the potential to obtain biased estimates of parasite (and host) traits when key biological processes are not considered. Despite generating infection dynamics using a fixed parasite developmental cycle length, we find that known sources of measurement bias in parasite stage and abundance data can affect estimates of parasite developmental duration, with stage misclassification driving inferences about extended cycle length. We discuss alternative protocols and statistical methods that can mitigate such misestimation.     

Role network measures to assess healthcare team adaptation to complex situations: the case of venous thromboembolism prophylaxis

Hospitals are complex environments that rely on clinicians working together to provide appropriate care to patients. These clinical teams adapt their interactions to meet changing situational needs. Venous thromboembolism (VTE) prophylaxis is a complex process that occurs throughout a patient’s hospitalisation, presenting five stages with different levels of complexity: admission, interruption, re-initiation, initiation, and transfer. The objective of our study is to understand how the VTE prophylaxis team adapts as the complexity in the process changes; we do this by using social network analysis (SNA) measures. We interviewed 45 clinicians representing 9 different cases, creating 43 role networks. The role networks were analysed using SNA measures to understand team changes between low and high complexity stages. When comparing low and high complexity stages, we found two team adaptation mechanisms: (1) relative increase in the number of people, team activities, and interactions within the team, or (2) relative increase in discussion among the team, reflected by an increase in reciprocity.

 

Practitioner Summary: The reason for this study was to quantify team adaptation to complexity in a process using social network analysis (SNA). The VTE prophylaxis team adapted to complexity by two different mechanisms, by increasing the roles, activities, and interactions among the team or by increasing the two-way communication and discussion throughout the team. We demonstrated the ability for SNA to identify adaptation within a team.     

Stabilization of Sn Anode through Structural Reconstruction of a Cu–Sn Intermetallic Coating Layer

The metallic tin (Sn) anode is a promising candidate for next-generation lithium-ion batteries (LIBs) due to its high theoretical capacity and electrical conductivity. However, Sn suffers from severe mechanical degradation caused by large volume changes during lithiation/delithiation, which leads to a rapid capacity decay for LIBs application. Herein, a Cu–Sn (e.g., Cu₃Sn) intermetallic coating layer (ICL) is rationally designed to stabilize Sn through a structural reconstruction mechanism. The low activity of the Cu–Sn ICL against lithiation/delithiation enables the gradual separation of the metallic Cu phase from the Cu–Sn ICL, which provides a regulatable and appropriate distribution of Cu to buffer volume change of Sn anode. Concurrently, the homogeneous distribution of the separated Sn together with Cu promotes uniform lithiation/delithiation, mitigating the internal stress. In addition, the residual rigid Cu–Sn intermetallic shows terrific mechanical integrity that resists the plastic deformation during the lithiation/delithiation. As a result, the Sn anode enhanced by the Cu–Sn ICL shows a significant improvement in cycling stability with a dramatically reduced capacity decay rate of 0.03% per cycle for 1000 cycles. The structural reconstruction mechanism in this work shines a light on new materials and structural design that can stabilize high-performance and high-volume-change electrodes for rechargeable batteries and beyond.     

Copper@ZIF-8 Core-Shell Nanowires for Reusable Antimicrobial Face Masks

SARS-CoV-2 and other respiratory viruses spread via aerosols generated by infected people. Face masks can limit transmission. However, widespread use of disposable masks consumes tremendous resources and generates waste. Here, a novel material for treating blown polypropylene filtration media used in medical-grade masks to impart antimicrobial activity is reported. To produce thin copper@ZIF-8 core-shell nanowires (Cu@ZIF-8 NWs), Cu NWs are stabilized using a pluronic F-127 block copolymer, followed by growth of ZIF-8 to obtain uniform core-shell structures. The Cu@ZIF-8 NWs are applied to filtration media by dip coating. Aerosol filtration efficiency decreases upon exposure to ethanol (solvent for dip-coating), but increases with addition of Cu@ZIF-8 NWs. Cu@ZIF-8 NWs shows enhanced antibacterial activity, compared to Cu NWs or ZIF-8 alone, against Streptococcus mutans and Escherichia coli. Antiviral activity against SARS-CoV-2 is assayed using virus-infected Vero E6 cells, demonstrating 55% inhibition of virus replication after 48 h by 1 µg of Cu@ZIF-8 NWs per well. Cu@ZIF-8 NWs’ cytotoxicity is tested against four cell lines, and their effect on inflammatory response in A549 cells is examined, demonstrating good biocompatibility. This low-cost, scalable synthesis and straightforward deposition of Cu@ZIF-8 NWs onto filter media has great potential to reduce disease transmission, resource consumption, and environmental impact of waste.