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Jinty Nelson in Thirteen Articles
Get PDFThis collection gathers thirteen contributions by a number of historians, friends, colleagues and/or students of Jinty’s, who were asked to pick their favourite article by her and say a few words about it for an event held in her memory on 15 January 2025 at King’s College London. We offer this collection in print now for a wider audience not so much because it has any claim to be exhaustive or authoritative, but because taken all together these pieces seemed to add up to a useful retrospective on Jinty’s work, its wider context, and its impact on the field over the decades. We hope that, for those who know her work well already, this may be an opportunity to remember some of her classic (and a few less classic) articles, while at the same time serving as an accessible introduction to her research for anyone who knew her without necessarily knowing about her field, as well as for a new and younger generation of readers
Heterodinuclear Co(III)Na(I) Catalysts for the Ring-Opening Copolymerization of Propene Oxide and Carbon Dioxide
Get PDFThe ring-opening copolymerization of propene oxide and carbon dioxide is an effective route to make polycarbonates. Catalysts showing high activities, high polymer selectivities, molecular weight control, and tolerance to impurities are rare. Here, a series of four Co(III)Na(I) catalysts are tested for the ring-opening copolymerization of propene oxide and carbon dioxide. The complexes have systematic variations in the ligand structure in which both Co(III) and Na(I) binding sites are modified. Significant differences in catalyst performance are observed, with the lead catalyst featuring six oxygen donors and an ethylene diamine linker. This catalyst shows excellent activity and high poly(propene carbonate) selectivity at elevated temperatures (TOF = 1428 h–1, poly(propene carbonate) selectivity = 98%, 20 bar CO2, 70 °C), outperforming analogous Co(III)K(I) catalysts. These results inform on the optimal coordination environment and operating conditions for the Co(III)Na(I) catalysts and highlight the benefits of using Na(I) relative to heavier s-block metals in the heterodinuclear catalysts
Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry
Get PDFAge at onset of walking is an important early childhood milestone which is used clinically and in public health screening. In this genome-wide association study meta-analysis of age at onset of walking (N = 70,560 European-ancestry infants), we identified 11 independent genome-wide significant loci. SNP-based heritability was 24.13% (95% confidence intervals = 21.86–26.40) with ~11,900 variants accounting for about 90% of it, suggesting high polygenicity. One of these loci, in gene RBL2, co-localized with an expression quantitative trait locus (eQTL) in the brain. Age at onset of walking (in months) was negatively genetically correlated with ADHD and body-mass index, and positively genetically correlated with brain gyrification in both infant and adult brains. The polygenic score showed out-of-sample prediction of 3–5.6%, confirmed as largely due to direct effects in sib-pair analyses, and was separately associated with volume of neonatal brain structures involved in motor control. This study offers biological insights into a key behavioural marker of neurodevelopment
Management capacity of primary healthcare facilities in low- and middle-income countries: A scoping review
Get PDFHow health facilities are managed determines their performance and health service delivery. Management capacity of health facilities comprises the competency of managers at the individual level and the management support and work environment in their institutions. Evidence shows this management capacity influences service delivery and performance of the facility. For LMICs, there are evidence gaps as existing evidence is scarce, varied in the assessment of management capacity of PHC facilities and report a measurement gap due to the scarcity of assessment tools contextualised to the LMIC PHC setting. Our review aims to address these gaps by mapping and summarising the existing literature on management capacity of PHC facilities in LMICs, its components and performance across these components, providing evidence on what needs to be improved for better service delivery. We used Arksey and O`Malley`s scoping review methodology. We searched PubMed, Scopus, Web of Science and Google Scholar and hand-checked reference lists. We synthesized findings using a thematic approach. We included 21 articles out of the 3867 articles gotten. Individual capacity consisted of managerial competencies grouped into seven groups: (1) communication and information management, (2) financial management and planning, (3) human resource, supportive and performance management, (4) community stakeholder and engagement, (5) target setting and problem solving, (6) leadership and (7) situational analysis. Institutional capacity included functional support systems grouped into; (1) availability of resources, (2) support to undertake duties and (3) clear roles and responsibilities. Gaps were prevalent across individual and institutional capacities. There were deficiencies in the managerial competencies of the managers and the functional support systems were not adequate. These negatively affected facility service delivery and performance. There is still a scarcity of studies hence more research is needed. Furthermore, interventions such as training and supportive supervision should be considered in improving the managerial competencies of managers
Sjögren’s disease autoantigen TRIM21/Ro52 is exposed during lytic cell death, facilitates immune complex formation and activates macrophages
No full textSjögren’s disease (SjD) causes localised inflammation of the lacrimal and salivary glands (SGs), and autoantibody production against ubiquitously expressed intracellular proteins such as TRIM21/Ro52 and TROVE2/Ro60. TRIM21 has vital intracellular roles, as an Fc receptor and E3 ubiquitin ligase. It binds antibody Fc domains on opsonised pathogens, which have escaped extracellular immunity and entered cytosols. TRIM21 ubiquitinates these pathogenic targets, driving their proteasomal degradation. However, whilst the intracellular functions of TRIM21 are well-established, how and why TRIM21 becomes an autoantigen in SjD remains unclear.
Previous studies suggest apoptosis promotes self-antigen release, triggering germinal centre (GC) reactions for autoantibody production. However, apoptosis is generally anti-inflammatory and thus more recently, lytic cell death has been proposed as a mechanism for driving inflammation in autoimmune diseases. Therefore, we first aimed to identify the location and regulation of TRIM21 expression in murine and human cells. We then tested whether TRIM21 is preferentially released during lytic forms of cell death (pyroptosis, necroptosis or necrosis), which may promote autoimmune responses upon concomitant release of inflammatory alarmins. We found that TRIM21 is expressed ubiquitously in cells and tissues and can be further upregulated following pathogenic (e.g. LPS and Poly I:C) or cytokine (e.g. IFN) stimulation. TRIM21 is released upon lytic cell death (pyroptosis/necroptosis) but not apoptosis. Instead, during apoptosis, TRIM21-GFP punctae localised within apoptotic blebs and were not released into the cell supernatant.
Earlier research demonstrates that intracellular TRIM21 binds antibody Fc with very high affinity. However, whether extracellular TRIM21 could maintain its antibody-binding capacity was unknown. We analysed TRIM21-antibody binding by ELISA, immunoprecipitation (IP) and non-denaturing protein-complex separation (Native Blue-PAGE). We showed that TRIM21 forms immune complexes (ICs) with circulating antibodies via its PRYSPRY Fc-interacting domain. Importantly, these complexes were even larger with plasma antibodies from TRIM21/Ro52-seropositive SjD patients, where TRIM21-antibody interactions were mediated via both Fc- and F(ab’)2 domains.
ICs are pathogenic in autoimmune diseases such as systemic lupus erythematosus (SLE), and may promote inflammation and antigen presentation. Thus we sought to explore the uptake and functional consequences of TRIM21-ICs in vitro. We fed TRIM21 and TRIM21-ICs of different sizes to macrophages. We showed that larger ICs are taken up more efficiently and facilitate stronger pro-inflammatory cytokine secretion, compared to soluble, free TRIM21. This was also validated by gene expression analyses, with macrophages showing inflammatory and metabolic transcriptional changes.
Antigen presentation is an important mechanism for driving autoimmune, antigen-specific immune reactions. Therefore, we tested whether TRIM21 could drive antigen cross-presentation, by employing the OT-I ovalbumin (OVA) TCR-transgenic mouse system. We generated TRIM21-OVA ICs, which we fed to murine macrophages and then detected CD8+ T cell activation, as evidence for cross-presentation. TRIM21-OVA ICs were more efficiently cross-presented that OVA alone, suggesting that extracellular TRIM21 may be able to bind opsonised antigens and enhance their cross-presentation.
We suggest such TRIM21-dependent mechanisms of inflammation and antigen presentation may perpetuate additional SG damage in SjD. This may drive cycles of further tissue destruction, TRIM21 antigen release, IC formation and cross-presentation. Therefore, TRIM21’s ability to bind antibody Fc and form ICs causes it to be inherently autoimmunogenic
The genome sequence of a lauxanid fly, <i>Meiosimyza decipiens</i> (Loew, 1847)
Get PDFWe present a genome assembly from a male Meiosimyza decipiens (fly; Arthropoda; Insecta; Diptera; Lauxaniidae). The genome sequence has a total length of 436.39 megabases. Most of the assembly (99.68%) is scaffolded into 6 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.39 kilobases in length
Building Immunocompetent Cerebral Organoids From a Developmental Perspective
Get PDFCerebral organoids derived from human induced pluripotent stem cells (iPSCs) are increasingly becoming essential tools to study the human brain, from understanding pathological mechanisms in neurodevelopmental, neurodegenerative, and infectious diseases to identifying genetic risks and biomarkers. To resemble the brain environment, cerebral organoids must contain microglia, the resident macrophages of the brain parenchyma that are essential for its homeostasis. As microglia derive from the yolk sac, they are not present in conventional brain organoids, which are generated by reprogramming iPSCs towards the neuroectodermal lineage and must be exogenously incorporated through a variety of strategies. Once in the organoid parenchyma, microglia must recapitulate their developmental milestones to achieve full immunocompetence, reaching a mature transcriptional profile and morphology, a tessellated distribution, efficient phagocytosis, and controlled inflammatory responses. In this review, we will summarize recent protocols that have been developed to generate human microglial‐containing cerebral organoids (MCCOs), focusing on the methods used to assess the level of microglial maturation compared to their in vivo counterparts. We provide a series of recommendations to assess microglial immunocompetence using stringent quantitative approaches that will promote developing standardized protocols to culture MCCOs
Superheating gold beyond the predicted entropy catastrophe threshold
Get PDFIn their landmark study1, Fecht and Johnson unveiled a phenomenon that they termed the ‘entropy catastrophe’, a critical point where the entropy of superheated crystals equates to that of their liquid counterparts. This point marks the uppermost stability boundary for solids at temperatures typically around three times their melting point. Despite the theoretical prediction of this ultimate stability threshold, its practical exploration has been prevented by numerous intermediate destabilizing events, colloquially known as a hierarchy of catastrophes2, 3, 4–5, which occur at far lower temperatures. Here we experimentally test this limit under ultrafast heating conditions, directly tracking the lattice temperature by using high-resolution inelastic X-ray scattering. Our gold samples are heated to temperatures over 14 times their melting point while retaining their crystalline structure, far surpassing the predicted threshold and suggesting a substantially higher or potentially no limit for superheating. We point to the inability of our samples to expand on these very short timescales as an important difference from previous estimates. These observations provide insights into the dynamics of melting under extreme conditions
Beyond the tangible: exploring the spatiality of magic across curse tablets, literary, and para-literary sources of the Roman era
No full textThis thesis explores the spatial dimensions of ancient magic through a diverse range of sources, with a primary focus on ancient curse tablets (defixiones) from the Roman world. Central to the study are the contexts of their deposition, the associated ritual practices, and their socio-cultural significance. Spanning the Early Imperial Period to Late Antiquity, the study investigates how these ritualised objects, inscribed with invocations to deities and ill wishes directed at specific targets, were embedded in physical, conceptual, and cultural landscapes. Using spatial theory as a framework, this research explores the interplay between place, space, and landscape, introducing the concept of the cursescape to define the dynamic environments shaped by curse technology.
Part One analyses the contexts of deposition, categorising sites as structured—e.g., sanctuaries such as the Temple of Demeter and Kore at Corinth and the Sulis Minerva Temple at Bath—and non-structured, including rivers, wells, and private residences. Comparative analysis reveals how awareness of/concepts of spatial memory, secrecy, and ritual pollution influenced these choices. It is shown that structured sites reflect traditions of communal magical practices, while non-structured settings highlight personalised and localised uses of curse technology.
Part Two shifts the focus to the texts of curses as expressions of everyday cult(ure). Within this realm, they articulate anxieties concerning interpersonal conflict—ranging from theft and competition to legal disputes—displaying dynamic linguistic innovation, ritual metaphors, and performative strategies. The influence of oral traditions and the professionalisation of scribes is also explored, emphasising the socio-cultural embeddedness of these texts.
Part Three extends the analysis to literary and para-literary representations of magic, contrasting the curses that form part of material culture with depictions in Roman literature and the magical papyri. The perception and reflection of the integration of magical practices into daily life (as illustrated in Parts One and Two) are complemented by a dystopian and transgressive framing of magic in our literary portrayals.
Through its interdisciplinary approach, the study challenges the dichotomy between magic and religion, offering fresh insights into ancient spiritual practices, social dynamics, and the ways individuals navigated uncertainty through supernatural means
Chemical tuning of quantum spin-electric coupling in molecular magnets
Get PDFControlling quantum spins using electric rather than magnetic fields promises significant architectural advantages for developing quantum technologies. In this context, spins in molecular magnets offer tunability of spin-electric couplings (SEC) by rational chemical design. Here we demonstrate systematic control of SECs in a family of Mn(II)-containing molecules by varying the coordination environment of the spin centre. The trigonal bipyramidal (tbp) molecular structure with C3 symmetry leads to a significant molecular electric dipole moment that is directly connected to its magnetic anisotropy. The interplay between these two features gives rise to significant experimentally observed SECs, which can be rationalised by wavefunction theoretical calculations. Our findings guide strategies for the development of electrically controllable molecular spin qubits for quantum technologies