A thalamic-primary auditory cortex circuit mediates resilience to stress.

Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.

Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.

Acquired stress resilience through bacteria-to-nematode interdomain horizontal gene transfer.

Natural selection drives the acquisition of organismal resilience traits to protect against adverse environments. Horizontal gene transfer (HGT) is an important evolutionary mechanism for the acquisition of novel traits, including metazoan acquisitions in immunity, metabolic, and reproduction function via interdomain HGT (iHGT) from bacteria. Here, we report that the nematode gene rml-3 has been acquired by iHGT from bacteria and that it enables exoskeleton resilience and protection against environmental toxins in Caenorhabditis elegans. Phylogenetic analysis reveals that diverse nematode RML-3 proteins form a single monophyletic clade most similar to bacterial enzymes that biosynthesize L-rhamnose, a cell-wall polysaccharide component. C. elegans rml-3 is highly expressed during larval development and upregulated in developing seam cells upon heat stress and during the stress-resistant dauer stage. rml-3 deficiency impairs cuticle integrity, barrier functions, and nematode stress resilience, phenotypes that can be rescued by exogenous L-rhamnose. We propose that interdomain HGT of an ancient bacterial rml-3 homolog has enabled L-rhamnose biosynthesis in nematodes, facilitating cuticle integrity and organismal resilience to environmental stressors during evolution. These findings highlight a remarkable contribution of iHGT on metazoan evolution conferred by the domestication of a bacterial gene.

Critical slowing down of the Amazon forest after increased drought occurrence.

Dynamic ecosystems, such as the Amazon forest, are expected to show critical slowing down behavior, or slower recovery from recurrent small perturbations, as they approach an ecological threshold to a different ecosystem state. Drought occurrences are becoming more prevalent across the Amazon, with known negative effects on forest health and functioning, but their actual role in the critical slowing down patterns still remains elusive. In this study, we evaluate the effect of trends in extreme drought occurrences on temporal autocorrelation (TAC) patterns of satellite-derived indices of vegetation activity, an indicator of slowing down, between 2001 and 2019. Differentiating between extreme drought frequency, intensity, and duration, we investigate their respective effects on the slowing down response. Our results indicate that the intensity of extreme droughts is a more important driver of slowing down than their duration, although their impacts vary across the different Amazon regions. In addition, areas with more variable precipitation are already less ecologically stable and need fewer droughts to induce slowing down. We present findings indicating that most of the Amazon region does not show an increasing trend in TAC. However, the predicted increase in extreme drought intensity and frequency could potentially transition significant portions of this ecosystem into a state with altered functionality.

Nonlethal deleterious mutation-induced stress accelerates bacterial aging.

Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms' long-term adaptation to new environments. However, loss-of-function mutations are often deleterious, triggering, in turn, cellular stress and complex homeostatic stress responses, called "allostasis," to promote cell survival. Here, we characterize the differential impacts of 65 nonlethal, deleterious single-gene deletions on Escherichia coli growth in three different growth environments. Further assessments of select mutants, namely, those bearing single adenosine triphosphate (ATP) synthase subunit deletions, reveal that mutants display reorganized transcriptome profiles that reflect both the environment and the specific gene deletion. We also find that ATP synthase α-subunit deleted (ΔatpA) cells exhibit elevated metabolic rates while having slower growth compared to wild-type (wt) E. coli cells. At the single-cell level, compared to wt cells, individual ΔatpA cells display near normal proliferation profiles but enter a postreplicative state earlier and exhibit a distinct senescence phenotype. These results highlight the complex interplay between genomic diversity, adaptation, and stress response and uncover an "aging cost" to individual bacterial cells for maintaining population-level resilience to environmental and genetic stress; they also suggest potential bacteriostatic antibiotic targets and -as select human genetic diseases display highly similar phenotypes, - a bacterial origin of some human diseases.

Ca2+-sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress.

Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that low concentrations of GPN rupture a small fraction of lysosomes, but surprisingly trigger Ca2+ release from nearly all. Chelating cytoplasmic Ca2+ makes lysosomes more sensitive to GPN-induced rupture, suggesting a role for Ca2+ in lysosomal membrane resilience. GPN-elicited Ca2+ release causes the Ca2+-sensor Apoptosis Linked Gene-2 (ALG-2), along with Endosomal Sorting Complex Required for Transport (ESCRT) proteins it interacts with, to redistribute onto lysosomes. Functionally, ALG-2, but not its ESCRT binding-disabled ΔGF122 splice variant, increases lysosomal resilience to osmotic stress. Importantly, elevating juxta-lysosomal Ca2+ without membrane damage by activating TRPML1 also recruits ALG-2 and ESCRTs, protecting lysosomes from subsequent osmotic rupture. These findings reveal that Ca2+, through ALG-2, helps bring ESCRTs to lysosomes to enhance their resilience and maintain organelle integrity in the face of osmotic stress.

Age-related behavioral resilience in smartphone touchscreen interaction dynamics.

We experience a life that is full of ups and downs. The ability to bounce back after adverse life events such as the loss of a loved one or serious illness declines with age, and such isolated events can even trigger accelerated aging. How humans respond to common day-to-day perturbations is less clear. Here, we infer the aging status from smartphone behavior by using a decision tree regression model trained to accurately estimate the chronological age based on the dynamics of touchscreen interactions. Individuals (N = 280, 21 to 87 y of age) expressed smartphone behavior that appeared younger on certain days and older on other days through the observation period that lasted up to ~4 y. We captured the essence of these fluctuations by leveraging the mathematical concept of critical transitions and tipping points in complex systems. In most individuals, we find one or more alternative stable aging states separated by tipping points. The older the individual, the lower the resilience to forces that push the behavior across the tipping point into an older state. Traditional accounts of aging based on sparse longitudinal data spanning decades suggest a gradual behavioral decline with age. Taken together with our current results, we propose that the gradual age-related changes are interleaved with more complex dynamics at shorter timescales where the same individual may navigate distinct behavioral aging states from one day to the next. Real-world behavioral data modeled as a complex system can transform how we view and study aging.

Transient social-ecological dynamics reveal signals of decoupling in a highly disturbed Anthropocene landscape.

Understanding the transient dynamics of interlinked social-ecological systems (SES) is imperative for assessing sustainability in the Anthropocene. However, how to identify critical transitions in real-world SES remains a formidable challenge. In this study, we present an evolutionary framework to characterize these dynamics over an extended historical timeline. Our approach leverages multidecadal rates of change in socioeconomic data, paleoenvironmental, and cutting-edge sedimentary ancient DNA records from China's Yangtze River Delta, one of the most densely populated and intensively modified landscapes on Earth. Our analysis reveals two significant social-ecological transitions characterized by contrasting interactions and feedback spanning several centuries. Initially, the regional SES exhibited a loosely connected and ecologically sustainable regime. Nevertheless, starting in the 1950s, an increasingly interconnected regime emerged, ultimately resulting in the crossing of tipping points and an unprecedented acceleration in soil erosion, water eutrophication, and ecosystem degradation. Remarkably, the second transition occurring around the 2000s, featured a notable decoupling of socioeconomic development from ecoenvironmental degradation. This decoupling phenomenon signifies a more desirable reconfiguration of the regional SES, furnishing essential insights not only for the Yangtze River Basin but also for regions worldwide grappling with similar sustainability challenges. Our extensive multidecadal empirical investigation underscores the value of coevolutionary approaches in understanding and addressing social-ecological system dynamics.

Monitoring resilience in bursts.

The possibility to anticipate critical transitions through detecting loss of resilience has attracted attention in many fields. Resilience indicators rely on the mathematical concept of critical slowing down, which means that a system recovers more slowly from external perturbations when it gets closer to tipping point. This decrease in recovery rate can be reflected in rising autocorrelation and variance in data. To test whether resilience is changing, resilience indicators are often calculated using a moving window in long, continuous time series of the system. However, for some systems, it may be more feasible to collect several high-resolution time series in short periods of time, i.e., in bursts. Resilience indicators can then be calculated to detect a change of resilience between such bursts. Here, we compare the performance of both methods using simulated data and showcase the possible use of bursts in a case study using mood data to anticipate depression in a patient. With the same number of data points, the burst approach outperformed the moving window method, suggesting that it is possible to downsample the continuous time series and still signal an upcoming transition. We suggest guidelines to design an optimal sampling strategy. Our results imply that using bursts of data instead of continuous time series may improve the capacity to detect changes in resilience. This method is promising for a variety of fields, such as human health, epidemiology, or ecology, where continuous monitoring can be costly or unfeasible.

Social-ecological vulnerability and risk of China's marine capture fisheries to climate change.

Climate change is a new disrupter to global fisheries systems and their governance frameworks. It poses a pressing management challenge, particularly in China, which is renowned as the world's largest fishing country and seafood producer. As climate change continues to intensify in the region and climate awareness grows within the country's national policy, the need to understand China's fisheries' resilience to the escalating climate crisis becomes paramount. In this study, we conduct an interdisciplinary analysis to assess the vulnerability and risk of China's marine capture fisheries in response to climate change. This study employs a spatially explicit, indicator-based approach with a coupled social-ecological framework, focusing on 67 species and 11 coastal regions. By integrating diverse sets of climatic, ecological, economic, societal, and governance indicators and information, we elucidate the factors that could hinder climate adaptation, including a limited understanding of fish early life stages, uncertainty in seafood production, unequal allocation and accessibility of resources, and inadequate consideration of inclusive governance and adaptive management. Our results show that species, which have managed to survive the stress of overfishing, demonstrate a remarkable ability to adapt to climate change. However, collapsing stocks such as large yellow croaker face a high risk due to the synergistic effects of inherent biological traits and external management interventions. We emphasize the imperative to build institutional, scientific, and social capacity to support fisheries adaptation. The scientific insights provided by this study can inform fisheries management decisions and promote the operationalization of climate-resilient fisheries in China and other regions.

A resilient and connected network of sites to sustain biodiversity under a changing climate.

Motivated by declines in biodiversity exacerbated by climate change, we identified a network of conservation sites designed to provide resilient habitat for species, while supporting dynamic shifts in ranges and changes in ecosystem composition. Our 12-y study involved 289 scientists in 14 study regions across the conterminous United States (CONUS), and our intent was to support local-, regional-, and national-scale conservation decisions. To ensure that the network represented all species and ecosystems, we stratified CONUS into 68 ecoregions, and, within each, we comprehensively mapped the geophysical settings associated with current ecosystem and species distributions. To identify sites most resilient to climate change, we identified the portion of each geophysical setting with the most topoclimate variability (high landscape diversity) likely to be accessible to dispersers (high local connectedness). These "resilient sites" were overlaid with conservation priority maps from 104 independent assessments to indicate current value in supporting recognized biodiversity. To identify key connectivity areas for sustaining species movement in response to climate change, we codeveloped a fine-scale representation of human modification and ran a circuit-theory-based analysis that emphasized movement potential along geographic climate gradients. Integrating areas with high values for two or more factors, we identified a representative, resilient, and connected network of biodiverse lands covering 35% of CONUS. Because the network connects climatic gradients across 250,000 biodiversity elements and multiple resilient examples of all geophysical settings in every ecoregion, it could form the spatial foundation for targeted land protection and other conservation strategies to sustain a diverse, dynamic, and adaptive world.

The vulnerability of aging states: A survival analysis across premodern societies.

How states and great powers rise and fall is an intriguing enigma of human history. Are there any patterns? Do polities become more vulnerable over time as they age? We analyze longevity in hundreds of premodern states using survival analysis to help provide initial insights into these questions. This approach is commonly used to study the risk of death in biological organisms or failure in mechanical systems. The results reveal that the risk of state termination increased steeply over approximately the first two centuries after formation and stabilized thereafter. This provides the first quantitative support for the hypothesis that the resilience of political states decreases over time. Potential mechanisms that could drive such declining resilience include environmental degradation, increasing complexity, growing inequality, and extractive institutions. While the cases are from premodern times, such dynamics and drivers of vulnerability may remain relevant today.

Rise of Ruppia in Chesapeake Bay: Climate change-driven turnover of foundation species creates new threats and management opportunities.

Global change has converted many structurally complex and ecologically and economically valuable coastlines to bare substrate. In the structural habitats that remain, climate-tolerant and opportunistic species are increasing in response to environmental extremes and variability. The shifting of dominant foundation species identity with climate change poses a unique conservation challenge because species vary in their responses to environmental stressors and to management. Here, we combine 35 y of watershed modeling and biogeochemical water quality data with species comprehensive aerial surveys to describe causes and consequences of turnover in seagrass foundation species across 26,000 ha of habitat in the Chesapeake Bay. Repeated marine heatwaves have caused 54% retraction of the formerly dominant eelgrass (Zostera marina) since 1991, allowing 171% expansion of the temperature-tolerant widgeongrass (Ruppia maritima) that has likewise benefited from large-scale nutrient reductions. However, this phase shift in dominant seagrass identity now presents two significant shifts for management: Widgeongrass meadows are not only responsible for rapid, extensive recoveries but also for the largest crashes over the last four decades; and, while adapted to high temperatures, are much more susceptible than eelgrass to nutrient pulses driven by springtime runoff. Thus, by selecting for rapid post-disturbance recolonization but low resistance to punctuated freshwater flow disturbance, climate change could threaten the Chesapeake Bay seagrass' ability to provide consistent fishery habitat and sustain functioning over time. We demonstrate that understanding the dynamics of the next generation of foundation species is a critical management priority, because shifts from relatively stable habitat to high interannual variability can have far-reaching consequences across marine and terrestrial ecosystems.

Phase-separation physics underlies new theory for the resilience of patchy ecosystems.

Spatial self-organization of ecosystems into large-scale (from micron to meters) patterns is an important phenomenon in ecology, enabling organisms to cope with harsh environmental conditions and buffering ecosystem degradation. Scale-dependent feedbacks provide the predominant conceptual framework for self-organized spatial patterns, explaining regular patterns observed in, e.g., arid ecosystems or mussel beds. Here, we highlight an alternative mechanism for self-organized patterns, based on the aggregation of a biotic or abiotic species, such as herbivores, sediment, or nutrients. Using a generalized mathematical model, we demonstrate that ecosystems with aggregation-driven patterns have fundamentally different dynamics and resilience properties than ecosystems with patterns that formed through scale-dependent feedbacks. Building on the physics theory for phase-separation dynamics, we show that patchy ecosystems with aggregation patterns are more vulnerable than systems with patterns formed through scale-dependent feedbacks, especially at small spatial scales. This is because local disturbances can trigger large-scale redistribution of resources, amplifying local degradation. Finally, we show that insights from physics, by providing mechanistic understanding of the initiation of aggregation patterns and their tendency to coarsen, provide a new indicator framework to signal proximity to ecological tipping points and subsequent ecosystem degradation for this class of patchy ecosystems.

Intentional release of native species undermines ecological stability.

The massive release of captive-bred native species ("intentional release") is a pervasive method to enhance wild populations of commercial and recreational species. However, such external inputs may disrupt the sensitive species interactions that allow competing species to coexist, potentially compromising long-term community stability. Here, we use theory and long-term data of stream fish communities to show that intentional release destabilizes community dynamics with limited demographic benefit to the enhanced species. Our theory predicted that intentional release intensifies interspecific competition, facilitating the competitive exclusion of unenhanced species that otherwise stably coexist. In parallel, the excessive input of captive-bred individuals suppressed the natural recruitment of the enhanced species via intensified within-species competition. Consequently, the ecological community with the intentional release is predicted to show reduced community density with unstable temporal dynamics. Consistent with this prediction, stream fish communities showed greater temporal fluctuations and fewer taxonomic richness in rivers with the intensive release of hatchery salmon-a major fishery resource worldwide. Our findings alarm that the current overreliance on intentional release may accelerate global biodiversity loss with undesired consequences for the provisioning of ecosystem services.

Brain aerobic glycolysis and resilience in Alzheimer disease.

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aß) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher than that seen in cognitively unimpaired, amyloid negative adults. Similar findings were not seen for blood flow nor oxygen consumption. Finally, in cognitively unimpaired adults, white matter hyperintensity burden was found to be specifically associated with decreased youthful brain AG. Our results suggest that AG may have a role in the resilience and/or response to early stages of amyloid pathology and that age-related white matter disease may impair this process.

Intrinsic neural diversity quenches the dynamic volatility of neural networks.

Heterogeneity is the norm in biology. The brain is no different: Neuronal cell types are myriad, reflected through their cellular morphology, type, excitability, connectivity motifs, and ion channel distributions. While this biophysical diversity enriches neural systems' dynamical repertoire, it remains challenging to reconcile with the robustness and persistence of brain function over time (resilience). To better understand the relationship between excitability heterogeneity (variability in excitability within a population of neurons) and resilience, we analyzed both analytically and numerically a nonlinear sparse neural network with balanced excitatory and inhibitory connections evolving over long time scales. Homogeneous networks demonstrated increases in excitability, and strong firing rate correlations-signs of instability-in response to a slowly varying modulatory fluctuation. Excitability heterogeneity tuned network stability in a context-dependent way by restraining responses to modulatory challenges and limiting firing rate correlations, while enriching dynamics during states of low modulatory drive. Excitability heterogeneity was found to implement a homeostatic control mechanism enhancing network resilience to changes in population size, connection probability, strength and variability of synaptic weights, by quenching the volatility (i.e., its susceptibility to critical transitions) of its dynamics. Together, these results highlight the fundamental role played by cell-to-cell heterogeneity in the robustness of brain function in the face of change.

Neuronal morphology enhances robustness to perturbations of channel densities.

Biological neurons show significant cell-to-cell variability but have the striking ability to maintain their key firing properties in the face of unpredictable perturbations and stochastic noise. Using a population of multi-compartment models consisting of soma, neurites, and axon for the lateral pyloric neuron in the crab stomatogastric ganglion, we explore how rebound bursting is preserved when the 14 channel conductances in each model are all randomly varied. The coupling between the axon and other compartments is critical for the ability of the axon to spike during bursts and consequently determines the set of successful solutions. When the coupling deviates from a biologically realistic range, the neuronal tolerance of conductance variations is lessened. Thus, the gross morphological features of these neurons enhance their robustness to perturbations of channel densities and expand the space of individual variability that can maintain a desired output pattern.

A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium.

The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as the known Toll-regulated antimicrobial peptide (AMP) genes are active only against filamentous fungi and not against Gram-positive bacteria or yeasts. Besides AMPs, two families of peptides secreted in response to infectious stimuli that activate the Toll pathway have been identified, namely Bomanins and peptides derived from a polyprotein precursor known as Baramicin A (BaraA). Unexpectedly, the deletion of a cluster of 10 Bomanins phenocopies the Toll mutant phenotype of susceptibility to infections. Here, we demonstrate that BaraA is required specifically in the host defense against Enterococcus faecalis and against the entomopathogenic fungus Metarhizium robertsii, albeit the fungal burden is not altered in BaraA mutants. BaraA protects the fly from the action of distinct toxins secreted by these Gram-positive and fungal pathogens, respectively, Enterocin V and Destruxin A. The injection of Destruxin A leads to the rapid paralysis of flies, whether wild type (WT) or mutant. However, a larger fraction of wild-type than BaraA flies recovers from paralysis within 5 to 10 h. BaraAs' function in protecting the host from the deleterious action of Destruxin is required in glial cells, highlighting a resilience role for the Toll pathway in the nervous system against microbial virulence factors. Thus, in complement to the current paradigm, innate immunity can cope effectively with the effects of toxins secreted by pathogens through the secretion of dedicated peptides, independently of xenobiotics detoxification pathways.

Advancing interdisciplinary science for disrupting wildlife trafficking networks.

Wildlife trafficking, whether local or transnational in scope, undermines sustainable development efforts, degrades cultural resources, endangers species, erodes the local and global economy, and facilitates the spread of zoonotic diseases. Wildlife trafficking networks (WTNs) occupy a unique gray space in supply chains-straddling licit and illicit networks, supporting legitimate and criminal workforces, and often demonstrating high resilience in their sourcing flexibility and adaptability. Authorities in different sectors desire, but frequently lack knowledge about how to allocate resources to disrupt illicit wildlife supply networks and prevent negative collateral impacts. Novel conceptualizations and a deeper scientific understanding of WTN structures are needed to help unravel the dynamics of interaction between disruption and resilience while accommodating socioenvironmental context. We use the case of ploughshare tortoise trafficking to help illustrate the potential of key advancements in interdisciplinary thinking. Insights herein suggest a significant need and opportunity for scientists to generate new science-based recommendations for WTN-related data collection and analysis for supply chain visibility, shifts in illicit supply chain dominance, network resilience, or limits of the supplier base.