Complementary approaches to understanding the plant circadian clock

Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock

Participation and retention in a green tourism certification scheme

Tourism certification schemes offer a transitional procedure to a more transparent and sustainable tourism product. Engaging current and previous Green Tourism Business Scheme (GTBS) members in Scotland, this research addresses issues of retention affecting progression of sustainable tourism supply. Quantitative analysis tracking GTBS members over three time points reveals 2% growth but conceals significant flux in membership. Retention was calculated at 66%, where business type analysis discloses distinct issues among accommodation providers with 42% departing the scheme. Decline is greatest among B&B and guesthouses (61%), where poor and falling recruitment coincides with very poor retention (33%). Our analysis demonstrates that slow growth in membership is primarily a result of enterprises choosing to leave the scheme, rather than poor recruitment. Questionnaires from past and present GTBS members (n = 109) confirm the importance of personal proenvironmental philosophies and perceived business benefits in attracting members, yet anticipated benefits do not always materialise. The main reasons for leaving the GTBS relate to membership cost and unrealised benefits. Lack of scheme awareness, management, criteria, bureaucracy and time commitment were further departure factors. The paper offers some suggestions to address issues and enhance retention leading to sustainable growth among tourism certification schemes

Induction of T Lymphocytes Specific for Bovine Viral Diarrhea Virus in Calves with Maternal Antibody

Passive antibody to bovine viral diarrhea virus (BVDV) acquired through colostrum intake may interfere with the development of a protective immune response by calves to this virus. The objective of this study was to determine if calves, with a high level of maternal antibody to bovine viral diarrhea virus (BVDV), develop CD4+, CD8+, or γδ T lymphocyte responses to BVDV in the absence of a measurable humoral immune response. Colostrum or milk replacer fed calves were challenged with virulent BVDV at 2-5 weeks of age and/or after maternal antibody had waned. Calves exposed to BVDV while passive antibody levels were high did not mount a measurable humoral immune response to BVDV. However, compared to nonexposed animals, these animals had CD4+, CD8+, and γδ T lymphocytes that were activated by BVDV after exposure to in vitro BVDV. The production of IFNγ by lymphocytes after in vitro BVDV exposure was also much greater in lymphocytes from calves exposed to BVDV in the presence of maternal antibody compared to the nonexposed calves. These data indicate that calves exposed to BVDV while maternal antibody levels are high can develop antigen specific CD4+, CD8+, and γδ T lymphocytes in the absence of an active antibody response. A manuscript presented separately demonstrates that the calves with T lymphocytes specific for BVDV in this study were also protected from virulent BVDV genotype 2 challenge after maternal antibody became undetectable

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy

Culture, Burnout, and Engagement: A Meta-Analysis on National Cultural Values as Moderators in JD-R Theory

Despite prominence and increasing application of the Job Demands‐Resources (JD‐R) theory across national contexts, the role of culture has not yet been systematically explored. We conducted a meta‐analysis of 132 independent samples from 120 studies across 5 global regions (total N = 101,073) to fill this void. Our paper responds to long‐standing concerns around neglecting differences in the relationships of workplace factors with burnout and engagement across national cultures by testing for a moderating role within JD‐R theory. Results suggest strong support for the direct job demands‐burnout and job resources‐engagement pathways. Regarding the role of culture, our study reveals moderating roles for five out of six cultural dimensions using Hofstede’s framework. Interestingly, these cultural dimensions present a moderating impact towards relationships with either job demands or job resources, yet not both. Our findings offer a valuable starting point for further theoretical developments that can impact international business and global mobility. While these insights suggest a role of national cultural context in JD‐R studies, sensitivity analyses showed that the findings were only partly stable

Repairing Trust in Organizations and Institutions: Toward a Conceptual Framework

Trust plays a fundamental role in facilitating social exchange, yet recent global events have undermined trust in many of society’s institutions and organizations. This raises the pertinent question of how trust in organizations and institutions can be restored once it has been lost. The emerging literature on trust repair is largely focused at the micro level, with limited examination of how these processes operate at the macro level and across levels. In this introductory essay, we show how the papers in this special issue each advance our understanding of macro-level trust repair. We draw on these papers, as well as the extant interdisciplinary literature, to propose an integrated conceptual model of six key mechanisms for restoring trust in organizations and institutions, highlighting the merits, limits and paradoxes of each. We conclude that no single mechanism can be relied on to rebuild organizational trust and identify a future research agenda for advancing scholarly understanding of organizational and institutional trust repair