Molecular mimicry in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

Logical interdependencies in infrastructure: What are they, how to identify them, and what do they mean for infrastructure risk analysis?

A useful theoretical lens that has emerged for understanding urban resilience is the four basic types of interdependencies in critical infrastructures: the physical, geographic, cyber, and logical types. This paper is motivated by a conceptual and methodological limitation-although logical interdependencies (where two infrastructures affect the state of each other via human decisions) are regarded as one of the basic types of interdependencies, the question of how to apply the notion and how to quantify logical relations remains under-explored. To overcome this limitation, this study focuses on institutions (rules), for example, rules and planned tasks guiding human interactions with one another and infrastructure. Such rule-mediated interactions, when linguistically expressed, have a syntactic form that can be translated into a network form. We provide a foundation to delineate these two forms to detect logical interdependence. Specifically, we propose an approach to quantify logical interdependence based on the idea that (1) there are certain network motifs indicating logical relations, (2) such network motifs can be discerned from the network form of rules, and that (3) the higher the frequency of these motifs between two infrastructures, the greater the extent of logical interdependency. We develop a set of such motifs and illustrate their usage using an example. We conclude by suggesting a revision to the original definition of logical interdependence. This rule-focused approach is relevant to understanding human error in risk analysis of socio-technical systems, as human error can be seen as deviations from constraints that lead to accidents.

Toward General Principles for Resilience Engineering.

Maintaining the performance of infrastructure-dependent systems in the face of surprises and unknowable risks is a grand challenge. Addressing this issue requires a better understanding of enabling conditions or principles that promote system resilience in a universal way. In this study, a set of such principles is interpreted as a group of interrelated conditions or organizational qualities that, taken together, engender system resilience. The field of resilience engineering identifies basic system or organizational qualities (e.g., abilities for learning) that are associated with enhanced general resilience and has packaged them into a set of principles that should be fostered. However, supporting conditions that give rise to such first-order system qualities remain elusive in the field. An integrative understanding of how such conditions co-occur and fit together to bring about resilience, therefore, has been less clear. This article contributes to addressing this gap by identifying a potentially more comprehensive set of principles for building general resilience in infrastructure-dependent systems. In approaching this aim, we organize scattered notions from across the literature. To reflect the partly self-organizing nature of infrastructure-dependent systems, we compare and synthesize two lines of research on resilience: resilience engineering and social-ecological system resilience. Although some of the principles discussed within the two fields overlap, there are some nuanced differences. By comparing and synthesizing the knowledge developed in them, we recommend an updated set of resilience-enhancing principles for infrastructure-dependent systems. In addition to proposing an expanded list of principles, we illustrate how these principles can co-occur and their interdependencies.

Sociohydrology: Scientific Challenges in Addressing the Sustainable Development Goals.

The Sustainable Development Goals (SDGs) of the United Nations Agenda 2030 represent an ambitious blueprint to reduce inequalities globally and achieve a sustainable future for all mankind. Meeting the SDGs for water requires an integrated approach to managing and allocating water resources, by involving all actors and stakeholders, and considering how water resources link different sectors of society. To date, water management practice is dominated by technocratic, scenario-based approaches that may work well in the short term but can result in unintended consequences in the long term due to limited accounting of dynamic feedbacks between the natural, technical, and social dimensions of human-water systems. The discipline of sociohydrology has an important role to play in informing policy by developing a generalizable understanding of phenomena that arise from interactions between water and human systems. To explain these phenomena, sociohydrology must address several scientific challenges to strengthen the field and broaden its scope. These include engagement with social scientists to accommodate social heterogeneity, power relations, trust, cultural beliefs, and cognitive biases, which strongly influence the way in which people alter, and adapt to, changing hydrological regimes. It also requires development of new methods to formulate and test alternative hypotheses for the explanation of emergent phenomena generated by feedbacks between water and society. Advancing sociohydrology in these ways therefore represents a major contribution toward meeting the targets set by the SDGs, the societal grand challenge of our time.

Effect of infrastructure design on commons dilemmas in social-ecological system dynamics.

The use of shared infrastructure to direct natural processes for the benefit of humans has been a central feature of human social organization for millennia. Today, more than ever, people interact with one another and the environment through shared human-made infrastructure (the Internet, transportation, the energy grid, etc.). However, there has been relatively little work on how the design characteristics of shared infrastructure affect the dynamics of social-ecological systems (SESs) and the capacity of groups to solve social dilemmas associated with its provision. Developing such understanding is especially important in the context of global change where design criteria must consider how specific aspects of infrastructure affect the capacity of SESs to maintain vital functions in the face of shocks. Using small-scale irrigated agriculture (the most ancient and ubiquitous example of public infrastructure systems) as a model system, we show that two design features related to scale and the structure of benefit flows can induce fundamental changes in qualitative behavior, i.e., regime shifts. By relating the required maintenance threshold (a design feature related to infrastructure scale) to the incentives facing users under different regimes, our work also provides some general guidance on determinants of robustness of SESs under globalization-related stresses.

Joint effects of voluntary participation and group selection on the evolution of altruistic punishment.

It is puzzling how altruistic punishment of defectors can evolve in large groups of nonrelatives, since punishers should voluntarily bear individual costs of punishing to benefit those who do not pay the costs. Although two distinct mechanisms have been proposed to explain the puzzle, namely voluntary participation and group-level competition and selection, insights into their joint effects have been less clear. Here we investigated what could be combined effects of these two mechanisms on the evolution of altruistic punishment and how these effects can vary with nonparticipants' individual payoff and group size. We modelled altruistic punishers as those who contribute to a public good and impose a fine on each defector, i.e., they are neither pure punishers nor excluders. Our simulation results show that voluntary participation has negative effects on the evolution of cooperation in small groups regardless of nonparticipants' payoffs, while in large groups it has positive effects within only a limited range of nonparticipants' payoff. We discuss that such asymmetric effects could be explained by evolutionary forces emerging from voluntary participation. Lastly, we suggest that insights from social science disciplines studying the exit option could enrich voluntary participation models.

Desiccation of a saline lake as a lock-in phenomenon: A socio-hydrological perspective.

Understanding of how anthropogenic droughts occur in socio-hydrological systems is critical in studying resilience of these systems. This is especially relevant when a "lock-in" toward watershed desiccation occurs as an emergent outcome of coupling among social dynamics and surface and underground water processes. How the various processes collectively fit together to reinforce such a lock-in and what may be a critical or ignored feedback worsening the state of the socio-hydrological systems remains poorly understood. Here we tackle this gap by focusing on the case of Lake Urmia in Iran, a saline lake that faces the same fate as that of Aral Sea due to over-extraction of water sources that feed the lake. We develop an integrative, system-level understanding of how various anthropogenic, surface and underground environmental processes collectively generate the water scarcity and soil salinization issues in the study case. To this end, we investigate a paradoxical phenomenon wherein the increase of soil salinity has not noticeably affected the level of vegetation cover in Lake Urmia Basin. The outcome of our analysis may provide useful insights for informing policymakers how to cope with drought and water scarcity issues in many fragile saline lakes around the world that are currently under threat by overexploitation.

Efficiency-fairness trade-offs in evacuation management of urban floods: The effects of the shelter capacity and zone prioritization.

With increasing flood risk, evacuation has become an important research topic in urban flood management. Urban flood evacuation is a complex problem due to i) the complex interactions among several components within a city and ii) the need to consider multiple, often competing, dimensions/objectives in evacuation analysis. In this study, we focused on the interplay between two such objectives: efficiency and fairness. We captured the evacuation process in a conceptual agent-based model (ABM), which was analyzed under different hard infrastructure and institutional arrangement conditions, namely, various shelter capacity distributions as a hard infrastructure property and simultaneous/staged evacuation as an institutional arrangement. Efficiency was measured as the time it takes for a person to evacuate to safety. Fairness was defined by how equally residents suffered from floods, and the level of suffering depended on the perceived risk and evacuation time. Our findings suggested that efficiency is more sensitive to the shelter capacity distribution, while fairness changes more notably according to the evacuation priority assigned to the divided zones in staged evacuation. Simultaneous evacuation generally tended to be more efficient but unfairer than staged evacuation. The efficiency-fairness trade-off was captured by Pareto-optimal strategies, among which uniform capacity cases led to a higher efficiency while prioritizing high-risk residents increases fairness. Strategies balancing efficiency and fairness featured a uniform capacity and prioritized high-risk residents at an intermediate time delay. These findings more clearly exposed the interactions between different factors and could be adopted as benchmarks to inform more complicated evacuation ABMs.