Omicron variant infection in inflammatory rheumatological conditions – outcomes from a COVID-19 naive population in Aotearoa New Zealand

Background: Due to geographic isolation and border controls Aotearoa New Zealand (AoNZ) attained high levels of population coronavirus disease-19 (COVID-19) vaccination before widespread transmission of COVID-19. We describe outcomes of SARS-CoV-2 infection (Omicron variant) in people with inflammatory rheumatic diseases in this unique setting. Methods: This observational study included people with inflammatory rheumatic disease and SARS-CoV-2 infection in AoNZ between 1 February and 30 April 2022. Data were collected via the Global Rheumatology Alliance Registry including demographic and rheumatic disease characteristics, and COVID-19 vaccination status and outcomes. Multivariable logistic regression was used to explore associations of demographic and clinical factors with COVID-19 hospitalisation and death. Findings: Of the 1599 cases included, 96% were from three hospitals that systematically identified people with inflammatory rheumatic disease and COVID-19. At time of COVID-19, 1513 cases (94.6%) had received at least two COVID-19 vaccinations. Hospitalisation occurred for 104 (6.5%) cases and 10 (0.6%) patients died. Lower frequency of hospitalisation was seen in cases who had received at least two vaccinations (5.9%), compared to the unvaccinated (20.6%) or those with a single vaccine dose (10.7%). In multivariable adjusted models, people with gout or connective tissue diseases (CTD) had increased risk of the combined outcome of hospitalisation/death, compared to people with inflammatory arthritis. Glucocorticoid and rituximab use were associated with increased rates of hospitalisation/death. All patients who died had three or more co-morbidities or were over 60 years old. Interpretation: In this cohort with inflammatory rheumatic diseases and high vaccination rates, severe outcomes from SARS-CoV-2 Omicron variant were relatively infrequent. The outcome of Omicron variant infection among vaccinated but SARS-CoV-2 infection-naive people with inflammatory rheumatic disease without other known risk factors were favourable. Funding: Financial support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) included management of COVID-19 Global Rheumatology Alliance funds

Mechanisms of Size Control and Polymorphism in Viral Capsid Assembly

We simulate the assembly dynamics of icosahedral capsids from subunits that interconvert between different conformations (or quasi-equivalent states). The simulations identify mechanisms by which subunits form empty capsids with only one morphology but adaptively assemble into different icosahedral morphologies around nanoparticle cargoes with varying sizes, as seen in recent experiments with brome mosaic virus (BMV) capsid proteins. Adaptive cargo encapsidation requires moderate cargo-subunit interaction strengths; stronger interactions frustrate assembly by stabilizing intermediates with incommensurate curvature. We compare simulation results to experiments with cowpea chlorotic mottle virus empty capsids and BMV capsids assembled on functionalized nanoparticles and suggest new cargo encapsidation experiments. Finally, we find that both empty and templated capsids maintain the precise spatial ordering of subunit conformations seen in the crystal structure even if interactions that preserve this arrangement are favored by as little as the thermal energy, consistent with experimental observations that different subunit conformations are highly similar

Modular assembly of proteins on nanoparticles

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold–sulfur bonds (Au–S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond

Drought Impact Is Alleviated in Sugar Beets (Beta vulgaris L.) by Foliar Application of Fullerenol Nanoparticles

Over the past few years, significant efforts have been made to decrease the effects of drought stress on plant productivity and quality. We propose that fullerenol nanoparticles (FNPs, molecular formula C-60(OH)(24)) may help alleviate drought stress by serving as an additional intercellular water supply. Specifically, FNPs are able to penetrate plant leaf and root tissues, where they bind water in various cell compartments. This hydroscopic activity suggests that FNPs could be beneficial in plants. The aim of the present study was to analyse the influence of FNPs on sugar beet plants exposed to drought stress. Our results indicate that intracellular water metabolism can be modified by foliar application of FNPs in drought exposed plants. Drought stress induced a significant increase in the compatible osmolyte proline in both the leaves and roots of control plants, but not in FNP treated plants. These results indicate that FNPs could act as intracellular binders of water, creating an additional water reserve, and enabling adaptation to drought stress. Moreover, analysis of plant antioxidant enzyme activities (CAT, APx and GPx), MDA and GSH content indicate that fullerenol foliar application could have some beneficial effect on alleviating oxidative effects of drought stress, depending on the concentration of nanoparticles applied. Although further studies are necessary to elucidate the biochemical impact of FNPs on plants; the present results could directly impact agricultural practice, where available water supplies are often a limiting factor in plant bioproductivity

Nothing New in the (North) East? Interpreting the Rhetoric and Reality of Japanese Corporate Governance

Japan finally seems to be pulling itself out of its lost decade (and a half) of economic stagnation. Some grudgingly or triumphantly attribute this to micro-economic reforms, freeing up arthritic markets, although there is also evidence that macro-economic policy failures have been a major cause of poor performance since the 1990s. Many point to overlapping transformations in corporate governance, broadly defined to cover relationships among managers and employees as well as between firms and outside shareholders, creditors, and other stakeholders. These relationships are in flux, with moves arguably favouring shareholders and more market-driven control mechanisms. It has certainly been a found decade for law reform in Japan, particularly in corporate law, with a plethora of legislative amendments commencing around 1993 and culminating in the enactment of a consolidated Company Law in 2005. This modernisation project, particularly since 2001, is reportedly aimed at (i) securing better corporate governance, (ii) bringing the law into line with a highly-developed information society, (iii) liberalising fundraising measures, (iv) bringing corporate law into line with the internationalization of corporate activity, and (v) modernizing terms and consolidating corporate law. Because the suite of revisions has moved away from strict mandatory rules set out originally in Japan\u27s Commercial Code of 1899, modeled primarily on German law, another growing perception is that Japanese corporate law and practice is or will soon be converging significantly on US models. However, assessments remain divided as to whether these moves in corporate governance and capitalism more generally in Japan amount to a new paradigm or regime shift . Focusing primarily on quite influential commentary in English, Part I of this paper outlines two pairs of views. It concludes that the most plausible assessment is of significant but gradual transformation towards a more market-driven approach, evident also in other advanced political economies. Drawing more generally from these often virulently divided views, Part II sets out five ways forward through the proliferating literature and source material on corporate governance in Japan. Particular care must be taken in: (i) selecting the temporal timeframe, (ii) selecting countries to compare, (iii) balancing black-letter law and broader socio-economic context, (iv) reflecting on and disclosing normative preferences, and (v) giving weight to processes as well as outcomes, when assessing change in Japan - and any other country\u27s governance system. Part III ends with a call for further research particularly on law- and policy-producing processes, rather than mainly outcomes. It also outlines the usefulness of this analytical framework for analysing the broader field of Corporate Social Responsibility, now emerging as the next major area of debate and transformation in Japan - as elsewhere