An Evidence-Based Approach to Covid-19 Pandemic Effects on Academics

We discuss our evidence-based approach to understanding and addressing the gendered impact of the pandemic on academics at Queen’s University Belfast, a research-intensive Russell Group UK University. The study was a collaboration between the University-wide Queen’s Gender Initiative, researchers, and Human Resources. A staff survey ran from 23 September until 30 October 2020, assessing academic productivity and personal factors including caring responsibilities, wellbeing, and time spent working. Data from 537 academics showed that multiple challenges were experienced with most of the day spent on work and caregiving tasks. The majority of worktime comprised teaching, at a cost to research productivity and personal wellbeing. These patterns were accentuated for female academics. From this holistic approach to understanding academics’ challenges, recommendations were presented to the University’s Executive Board and other high-level institutional committees. An Action Plan of sustainable solutions designed to mitigate the pandemic effect focused on promotion, research, workload support, and wellbeing. Furthermore, the findings directly informed policies to enhance working life, particularly in new models of flexible working. In summary, we report methodology to integrate research and centralized efforts to address the pandemic’s impact on academics, using a gender lens and incorporating complementarity of work, home-life and wellbeing

Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase

A paucity of novel acting antibacterials is in development to treat the rising threat of antimicrobial resistance, particularly in Gram-negative hospital pathogens, which has led to renewed efforts in antibiotic drug discovery. Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by stabilizing DNA-cleavage complexes, but their clinical utility has been compromised by resistance. We have identified a class of antibacterial thiophenes that target DNA gyrase with a unique mechanism of action and have activity against a range of bacterial pathogens, including strains resistant to fluoroquinolones. Although fluoroquinolones stabilize double-stranded DNA breaks, the antibacterial thiophenes stabilize gyrase-mediated DNA-cleavage complexes in either one DNA strand or both DNA strands. X-ray crystallography of DNA gyrase–DNA complexes shows the compounds binding to a protein pocket between the winged helix domain and topoisomerase-primase domain, remote from the DNA. Mutations of conserved residues around this pocket affect activity of the thiophene inhibitors, consistent with allosteric inhibition of DNA gyrase. This druggable pocket provides potentially complementary opportunities for targeting bacterial topoisomerases for antibiotic development

Change and Exchange: Economies of Literature and Knowledge in Early Modern Europe

The introductory essay outlines the way in which Change and Exchange places literature, and, in a wider sense, imaginative practice, at the centre of early modern economic knowledge. Probing the affinity between economic and metaphorical experience in terms of the transactional processes of change and exchange, it sets up the parameters within which the essays in the volume collectively forge a language to grasp early modern economic phenomena and their epistemic dimensions. It prepares the reader for the stimulating combination of materials that the book presents: the range of generic contexts engendered by emergent economic practices, structures of feeling and modes of knowing made available by new economic relations, and economies of transformation in discursive domains that are distinct from ‘economics’ as we understand it but cognate in their intuition of change and exchange as shaping agents

Chemotactic activity of extracellular nucleotideson human immune cells.

Purinergic P2 receptors are a class of plasma membrane receptors that are express in many tissues and are ligated by extracellular nucleotides [such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine 5–triphosphate (UTP) and uridine 5–diphosphate (UDP)], which are released as a consequence of cell damage, cell stress, bacterial infection or other noxious stimuli. According to the molecular structure, P2 receptors are divided into two subfamilies: P2X and P2Y receptors. The P2X receptors are ligand-gated channels, whereas P2Y receptors are G-protein-coupled seven-membrane-spanning receptors. Several studies indicate that nucleotides play an important role in immune response modulation through their action on multiple cell types, including monocytes, mast cells, dendritic cells, neutrophils, and eosinophils. Recent work by our group and others identified extracellular nucleotides as chemotaxins for various human immune cells, including eosinophils, neutrophils and dendritic cells. In this review, we summarise recent findings in this field and put forward a hypothesis on the role of P2 receptors in the early recruitment of human immune cells to the site of inflammation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening

AbstractThe identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.</jats:p