The key elements for fear extinction learning are unexpected omissions of expected aversive events, which are considered to be rewarding. Given its reception of reward information, we tested the hypothesis that the cerebellum contributes to reward-like prediction error processing driving extinction learning via its connections with the ventral tegmental area (VTA). Forty-three young and healthy participants performed a three-day fear conditioning paradigm in a 7T MR scanner. The cerebellum and VTA were active during unexpected omissions of aversive unconditioned stimuli in the initial extinction trials and in other learning phases, in line with the proposed role of prediction-error processing. Increased functional connectivity was observed between the cerebellum and VTA, indicating that they are functionally coupled during fear extinction learning. These results suggest that an interaction between the cerebellum and VTA should be incorporated into the existing model of the fear extinction network.
It is widely assumed that extinction occurs when environmental change outpaces a species' capacity to adapt. However, this hypothesis lacks support at the scale of global change, in part because the distribution of adaptation rates is unknown. Here, we test this idea by formulating a general model that predicts the distribution of adaptation rates across species. By assuming that species go extinct when they adapt too slowly, we derive a precise sigmoidal relationship between the rate of extinction and the rate of environmental change. We then show that above-background extinction rates in the fossil record follow the same sigmoidal response to global carbon-cycle change, indicating that the adaptation-rate distribution is effectively a distribution of critical thresholds. The inferred range of adaptation rates is similar to the spread of extreme rates of environmental change. This suggests that macroevolution may align the diversity of adaptation rates with environmental forcing, thereby setting the biosphere's sensitivity to global change. When rescaled to the slow rates of the geologic past, modern rates of environmental change appear to be below, but near, the point of maximal extinction susceptibility.
Climate change causes species redistribution and elevates extinction risk, making the early identification of vulnerable species critical for timely conservation. The International Union for Conservation of Nature Red List provides guidelines for assessing climate-related extinction risk using species distribution models and spatially explicit population models. Here we present a systematic evaluation of these guidelines based on simulations of virtual species with diverse life-history traits and range dynamics. We find that, while species distribution models provide adequate warning times for range-contracting species, they consistently underestimate extinction risk for range-shifting species. This is due to a concave relationship between population size and habitat loss, which contradicts the linear assumption in the Red List guidelines. Probabilistic extinction estimates from spatially explicit population models provide a belated warning for all species, particularly for highly threatened ones. Our results reveal key limitations of current Red List guidelines under climate change. Based on our findings, we provide tentative recommendations for updating the International Union for Conservation of Nature Red List guidelines.
Biodiversity loss is increasingly recognized as a source of systemic financial risk. The financial sector enables economic activities that exert pressure on ecosystems, sometimes far from where capital is held, so institutions in one region can enable biodiversity loss elsewhere by financing seemingly harmless sectors with value-chain links to harmful activities. We establish a novel correspondence matrix linking 104 environmental pressures to 124 IUCN biodiversity threats, and combine it with the GLORIA input-output model to quantify species extinction-risk for 164 countries. Particulate matter, land-use change, and nitrogenous gases are the most damaging pressures, exerted mainly by agriculture, manufacturing, and construction. Seventy-four countries are net importers of extinction risk and twenty-three net exporters; all twelve European countries analysed are importers, with approximately 40% of their financial assets linked to extinction-risk sectors. Because these pressures are so embedded in production, a 1% reduction in the extinction-risk footprint propagates almost one-for-one through the economy: output falls by about 0.88% on average, while firms' capacity to service debt weakens as revenues drop but interest obligations hold fixed. This exposes how structurally dependent financial systems are on nature-harming activity, supporting efforts to disclose and reduce holdings of assets linked to biodiversity loss.
Climate change affects the thermal environment in complex ways, including changing its temporal autocorrelation structure and intensifying heatwave regimes. While theory shows that higher temporal autocorrelation may exacerbate extinction risks, little work has been done to incorporate autocorrelation into thermal performance-based forecasting. Here, we pair stochastic simulation models of population dynamics with systematically generated temperature time series to determine when increasing the temporal autocorrelation of variable thermal environments generates greater extinction risks. We show that by clustering stressful conditions, increasing autocorrelation reduces the extent of warming and variability which populations with unimodal thermal tolerance can survive. We validate our predictions with a factorial experiment in protist microcosms, where we find that higher autocorrelation significantly elevates extinction risk across mean temperature treatments when environments include stressful temperatures. Taken together, these results provide the foundation for predicting which species and environments face the greatest thermal risks under increasing autocorrelation.
Studies can only guide conservation if their findings are informative at the scales at which practitioners and policy-makers operate. Yet, it is rarely tested whether large-scale studies reach similar conclusions to the smaller-scale studies on which conservation traditionally relies. We examine whether predictors of extinction risk are consistent across global, regional, and local scales, for 210 tropical forest mammal species (≥1 kg) that existed during the last 130,000 years, in 64 tropical forests, across three biogeographical realms. We found consistent predictors of extinction risk (body mass, generation length, diet, brain volume, and scansoriality) when analyses differed only in their spatial resolution. However, predictors differed when analyses also varied in their temporal extent. Macroecological findings about extinction risk can, thus, inform conservation at smaller scales, but they risk misidentifying threatened species if differences in temporal extent are not recognized.
Structural plasticity of dendritic spines has been observed during different learning paradigms, but how the functional dynamics of dendritic spines changes with memory processing and how these patterns relate to structural plasticity and dendritic integration remain unclear. Here, we perform longitudinal functional and structural in vivo imaging of the frontal association cortex in mice subject to fear conditioning and extinction over several days. We show that fear learning induced responsive spines that are more likely to be synchronous and clustered, which are consolidated over the following days but attenuated by extinction. We develop a causal inference model demonstrating that the active spine calcium signals during fear learning prevent the spines from being eliminated while promoting the elimination of neighboring spines after memory consolidation. Furthermore, the dendritic responsive signal reveals a learning-dependent tone discrimination pattern that is correlated to spines' structural remodeling. Our findings provide in vivo evidence consistent with functional-structural link of dendritic spines in a bidirectional learning paradigm.
We investigated mercury uptake by the polypod fern Dryopteris filix-mas from two mercury emission sites in the Czech Republic along transects of high to low soil Hg concentrations, with the aim to determine whether ferns can accumulate Hg in above-ground biomass where it could disrupt meiotic processes. We focus on Hg because it has been hypothesized to have caused widespread malformation of spores in ferns proliferating in conjunction with one of the Big Five mass extinction events at the end of the Triassic (201.5 Ma). Here, we show that Hg-concentrations in the roots of Dryopteris filix-mas reflect Hg-contamination in the topsoils, while Hg-concentrations in above-ground foliage appears not directly related to topsoil contamination. We employed thermal desorption to determine that fern root systems mainly absorb Hg from soils while above-ground biomass may also have received Hg via gaseous atmospheric uptake. Further detailed Hg-concentration analyses of various fern parts led to the new insight that the highest levels of Hg reside in the spore-producing sori where it could in theory disrupt sporogenesis. To further examine the role of Hg in driving malformations, we isolated Dryopteris spores for microscopic inspection. However, no clear correlation was established between the relative abundance of aberrant spores and Hg-contamination in ferns or soils. Hence, other factors such as temperature, moisture availability, hybridization and other toxic metals likely also influenced fern reproduction. Nevertheless, the high bioaccumulation of Hg in the spore-producing sori should stimulate further research into the binding and influence of Hg by ferns and its role as a driver of plant sterility across mass extinction events.
This study describes three new records of Icacinaceae-Punctiuga bachue gen. et sp. nov., Palaeophytocrene paramoae sp. nov., and Goweria bacatana sp. nov. from the Paleocene (Selandian-Thanetian) Bogotá Formation in Colombia-improving understanding of the distribution and evolution of this family in the Neotropics. We analyzed 47 fossil endocarps using microscopy and X-ray micro-computed tomography (μCT); we also studied the associated leaf assemblage in search of potential Icacinaceae foliage. We then compared the fossils to extant Icacinaceae specimens from herbaria and the existing literature. Punctiuga bachue features unique morphological traits that resemble and support a close affinity to Iodeae and Phytocreneae. The presence of Palaeophytocrene paramoae confirms Phytocreneae diversity in South America during the Paleocene, and the occurrence of leaves of Icacinaceae contribute to the history of Icacinaceae on the continent. Our results show a previously unacknowledged diversity of Icacinaceae in the Paleocene Neotropics, including two new species of endocarps with affinities to Phytocreneae and Iodeae, clades currently restricted to the Old World tropics. Our findings support an early Paleogene diversification of the family in the Neotropics and the extirpation of tropical lineages in the Neotropics during the later Cenozoic.
Over the last several decades, investigations of Earth's subsurface and other extremely low-biomass systems have refined our understanding of the environmental limits of life, driven by methodological advances that permit agnostic life detection of biology and their respective physical biosignatures and chemical biomarkers. These advances enable mission concepts centered on microbiological processes that facilitate identification of both active life and preserved biosignatures through measurements of metabolism and associated biochemical markers that, on Mars, are more likely to be retained below the surface. Terrestrially, although biological processes can exert a significant influence on Earth's crust, the presence of habitable conditions does not necessarily imply the existence of cellular life. The Viking missions constituted the first direct life-detection experiments on Mars but produced equivocal outcomes, prompting subsequent exploration strategies to emphasize surface habitability rather than direct biological testing. Leveraging progress in subsurface microbiology and planetary exploration, we contend that Mars missions are now poised to shift toward direct tests for extant microbial activity in the subsurface, with metabolic processes serving as a broadly applicable indicator of life.
A close but genetically divergent retrovirus named HIV-2 was discovered in 1986 in West African patients with AIDS negative or indeterminate for HIV-1 antibodies. Viral replication is lower in HIV-2, being plasma viremia often undetectable or low. As result, HIV-2 transmission either by sex or vertically, is lower compared to HIV-1. Alongside, CD4+ T-cell declines occur slowly and clinical manifestations of immunodeficiency may appear after 15 years in HIV-2 patients. Over 10% of HIV-2 carriers may remain asymptomatic lifelong. The susceptibility of HIV-2 to antiretroviral drugs is generally lower than for HIV-1, being non-nucleoside reverse transcriptase inhibitors non active. Some protease inhibitors, as darunavir, are effective. All integrase inhibitors block HIV-2, and either dolutegravir or bictegravir are the preferred drug choices. Specific viral load tests must be used to monitor HIV-2 plasma viremia. Trends in epidemiological surveys confirm that the HIV-2 pandemic is falling down with less infected persons yearly in endemic regions and globally.
Sixty-six million years ago, non-avian dinosaurs and other taxa went extinct during one of the largest mass extinctions in the history of life on Earth. The extinction was likely caused by an asteroid of unknown origin, responsible for the Chicxulub impact structure. Existing evidence identifies the impactor as an asteroid, similar to carbonaceous chondrites. However, carbonaceous chondrites are a diverse class of meteorites, leaving the exact nature of the impactor unclear. By measuring Ni isotopes in marine clays containing the impact ejecta, we constrain the impactor to one group of carbonaceous chondrites-CO chondrites-and some ungrouped chondrites. This study highlights the use of Ni isotopes in fingerprinting extraterrestrial materials on Earth. Given that CO chondrites are "dry" compared to the other carbonaceous chondrites and would have delivered much less volatiles, which are thought to be essential in causing the extinction, this work allows further studies of the mechanism behind the extinction.
Decreased connectivity within the default mode network (DMN) has been consistently implicated in post traumatic stress disorder (PTSD), but critical nodes through which traumatic stress changes DMN connectivity and DMN connectivity patterns that are linked to specific traumatic stress effects are not well understood. To address this, resting-state functional connectivity (rs-FConn) within the DMN was analyzed using modular and graph theory tools to characterize DMN connectivity changes brought on by single prolonged stress (SPS); a rat traumatic stress model. Results identified a set of negative edges that connect anterior and posterior DMN nodes. We refer to these as A-P edges and the anterior cingulate cortex (ACC) and rostral retrosplenial cortex (rRSC) were nodes that had the largest number of these edges. A-P edge frequency and graph connectivity measures decreased with a second fMRI scan in control rats and these decreases, and rRSC A-P edge frequency, were disrupted by SPS. Traumatic stress leads to deficits in extinction retention and to examine how DMN connectivity changed during extinction, we used correlated c-Fos levels among select DMN nodes to approximate DMN connectivity during fear/threat conditioning, and extinction learning and memory. Results suggest that SPS decreased DMN connectivity under most conditions, but enhanced DMN connectivity during extinction testing. Overall, the results of this study raise the possibility that while SPS does decrease DMN connectivity and disrupts changes in DMN connectivity brought on by a second fMRI scan, certain aspects of DMN connectivity are enhanced with SPS.
Islands with contrasting herbivore histories provide a natural framework to investigate the evolution of plant defenses. Theory predicts that on islands with historically intense vertebrate herbivory, juveniles maintain strong defenses while adults may reduce them once out of reach, whereas islands lacking vertebrate browsers show minimal ontogenetic differences and generally lower defenses. Alternatively, when extinct herbivores were particularly large, selection might also favor stronger adult defenses. Despite these theoretical expectations, empirical tests across multiple island systems remain scarce. In this study, we quantified leaf physical, chemical, and nutritional traits related to resistance and palatability in juvenile and adult individuals of 60 woody plant species across 33 families from six archipelagos: three with extinct large herbivores (New Zealand, New Caledonia, Mauritius) and three without vertebrate browsers (the Canary Islands, Azores, Channel Islands of California). We found that species from islands with historical herbivory exhibited overall lower defenses, with trait expression strongly shaped by ontogeny. Adults displayed higher phenolic concentrations and lower nutrient content than juveniles, reducing leaf palatability. By contrast, species from islands lacking herbivores showed no ontogenetic variation. These results reveal the lasting evolutionary legacy of extinct herbivores and show how herbivore history and ontogeny shape island plant defenses.
Drinking water is a rapid, instinctive behavior of mammals following stress. The role of such stress-induced water drinking behavior and its neural mechanisms remain poorly known. Here, we identify two sequentially activated neural circuits that respectively mediate stress-induced drinking behavior and reward encoding, which collectively promote the extinction of anxiety-like behaviors in mice. Specifically, mild short-term stress induces anxiety-like behaviors and activates glutamatergic neurons in the medial prefrontal cortex (mPFCGlu) projecting to glutamatergic neurons in the median preoptic nucleus (MnPOGlu), consequently driving drinking behavior in mice. This drinking behavior subsequently activates GABAergic neurons in the MnPO (MnPOGABA), which then inhibit GABAergic neurons in the ventral tegmental area (VTAGABA), leading to disinhibition of reward-encoding dopaminergic VTA neurons (VTADA), ultimately mediating the extinction of stress-induced anxiety-like behaviors. The present study defines cortical-hypothalamic-midbrain connections underlying the anxiety-relieving effects of drinking behavior, providing a circuit basis for innate stress coping strategies.
Exposure to a stressful trauma after successful treatment can lead to relapse, known as fear reinstatement. In the laboratory, fear reinstatement involves re-exposing individuals to an aversive unconditioned stimulus (US) after successful extinction learning, leading to the reinstatement of fear to a previously threatening conditioned stimulus (CS). While fear reinstatement is typically thought to evoke the return of old fear, preliminary evidence suggests that using a qualitatively different US during reinstatement can elicit new fear (i.e., this new US is expected to follow the CS instead of the US used in training). This study aimed to expand on this finding by examining safety behaviors, a behavioral response that minimizes US onset. To this end, participants first acquired conditioned fear and safety behaviors to the CS, followed by extinction learning to it. On the second day, some participants encountered a novel reinstatement US (Cross-US), while others received either the same US as in acquisition for reinstatement (Same-US) or no reinstatement manipulation (No-US). After reinstatement manipulation, the Cross-US group showed a larger increase in US avoidance and US expectancy to the novel US compared to the other groups. Our findings suggest that reinstatement elicits new fear and safety behaviors, underlying that treatment might benefit from addressing a range of safety behaviors.
Strain evolution poses a global threat, yet medical resources often fall short of meeting the demands of such public health emergencies. To examine how constrained medical resources and random factors influence disease transmission dynamics, this study incorporates the limited number of hospital beds into a stochastic infectious disease model that accounts for strain evolution and transmission rate affected by the logarithmic Ornstein-Uhlenbeck process. The primary contributions include deriving sufficient conditions that guarantee the existence, uniqueness and boundedness of the positive global solution for the stochastic model, identifying thresholds governing disease extinction and persistence and establishing sufficient conditions for the existence of a stationary distribution, based on which we compute the probability density function of the model to quantify the final size of the disease from a statistical perspective. Numerical simulations indicate that: (i) when strain 1 exhibits dominant transmissibility, it secures a dominant competitive position via its transmission advantage, while strain 2 sustains endemic transmission by exploiting recovered individuals, enabling the long-term coexistence of both strains. By contrast, when the two strains have comparable transmissibility, strain 1, which depends exclusively on susceptible individuals for transmission and survival, is eliminated via competitive exclusion by strain 2 (which can infect individuals recovered from strain 1), and is ultimately driven to extinction; (ii) for epidemic prevention and control, we should not only constrain the mean transmission rate of the disease below the epidemic threshold, but also reserve an adequate control safety margin against stochastic fluctuations in transmission rate; (iii) in the early stage of an epidemic when medical resources are scarce, it is necessary to rapidly expand hospital bed capacity. Once resource supply matches the epidemic demand, the focus of prevention and control should be shifted to optimizing the efficiency of resource scheduling. These results have certain significance for preventing and controlling diseases with such transmission patterns.
Chiral objects typically exhibit a different extinction for the two circular polarizations of light. Researchers often detect the chirality of objects by measuring this extinction difference employing circular dichroism spectroscopy. In this Letter, we present a new spectroscopy technique for detecting the chirality of dipolar objects based on measuring the Stokes parameters at any nonforward angle. The chirality measure we introduce effectively eliminates achiral background noise and is independent of both the object's concentration and the optical path length. Notably, when a solution contains both enantiomers of a chiral object, our method can discern which enantiomer predominates. Furthermore, we demonstrate that the technique is robust and verifiable in situ by measuring the Stokes vector at two different nonforward angles of choice.
Pancreatic ductal adenocarcinoma (PDAC) is driven by oncogenic KRAS in roughly 90% of cases, and KRAS-pathway inhibition has finally become clinically active. Durable benefit, however, will require identifying the adaptive and baseline vulnerabilities that shape response to KRAS inhibition. Two resistance mechanisms have been proposed separately in the literature - receptor-tyrosine-kinase bypass of KRAS, and dependence on the adhesion kinase FAK - but whether they are one target class or two, and which should partner a KRAS inhibitor, is unresolved. We integrate public perturbation, dependency, and survival data to nominate them as mechanistically separable candidate combination partners. Two findings define the separation. First, KRAS loss increases ERBB2/3 receptor expression. This appeared in both an inducible genetic KRAS-extinction model and, independently, in five PDAC lines treated with pharmacological KRAS-G12C/D inhibitors, while MAPK output collapsed as expected. The signal was clearest for ERBB2 and in the genetic model; in the small pharmacological cohort the effect was modest and its confidence intervals crossed zero, so we treat ERBB2/3 up-regulation as a candidate adaptive response - ERBB2-dominant and ERBB3-compatible - not a proven resistance mechanism. Second, focal adhesion kinase (FAK/PTK2) is the top-ranked standing druggable dependency within the KRAS/Src/RTK/adhesion network we examined (essential in 58% of pancreatic lines), yet it is not induced by KRAS shutdown. FAK dependency is present at baseline and, in DepMap, is statistically independent of a line's KRAS dependency (Spearman ρ = +0.05, n.s.) - a genuinely standing vulnerability rather than a KRAS-rebound effect. The candidate adaptive response and the standing dependency are not positively co-regulated across the perturbed lines (pooled Spearman ρ = -0.43, but n = 8 and n.s., so this cannot by itself establish independence); we therefore treat them as separable on mechanistic grounds - each nominated by different data and engaged by a different drug - rather than as statistically demonstrated independent programs. A Src-centered signaling-landscape analysis associates patient prognosis with the coordinated invasion-and-RTK program these nodes organize, rather than with any single transcript; this program remains prognostic after adjustment for a conventional EMT/stromal signature, which does not (Src-neighborhood per-standard-deviation OS hazard ratio 1.9, p ≈ 3 × 10⁻⁵; EMT signature null on adjustment). Together these results motivate a concrete, testable hypothesis: that FAK inhibition (a standing dependency) and ERBB inhibition (a candidate induced adaptive response) are separable candidate partners for a KRAS inhibitor, best evaluated as distinct arms of a biomarker-stratified platform. They also clarify why single-agent Src inhibition - a non-oncogene dependency tested as monotherapy, without a KRAS backbone, in advanced rather than micro-metastatic disease - was not positioned to surface either mechanism. No protein-level, phospho-signaling, or combination-response validation is performed here; all findings are computational nominations that require experimental validation before any clinical inference. KRAS inhibition is associated with an induced ERBB2/3 up-regulation - ERBB2-dominant, ERBB3-compatible - directionally reproduced across genetic KRAS extinction and pharmacological KRAS-G12C/D inhibition; the pharmacological effect is modest and underpoweredGenome-wide dependency nominates FAK - essential in 58% of pancreatic lines - as the top-ranked standing candidate co-target within the KRAS network; FAK dependency is present at baseline, statistically independent of KRAS dependency, and not co-regulated with the induced ERBB response Patient prognosis associates with a Src-organized invasion-and-RTK program, not with SRC , KRAS , or any single-gene transcript, and this program stays prognostic after adjustment for a conventional EMT/stromal signature The two mechanisms are separable on mechanistic grounds - nominated by different data and not positively co-regulated (though the direct correlation is underpowered, n = 8, n.s.) - motivating a multi-arm platform that could test FAK and ERBB partner arms as distinct hypotheses rather than one bundled combination. Blocking KRAS in pancreatic cancer is now clinically feasible, but resistance is the obstacle. Using only public data, Chen and colleagues nominate two mechanistically separable candidate combination partners for KRAS inhibitors: a candidate ERBB2-dominant adaptive (putative escape) response that is induced when KRAS is blocked, and FAK, the top-ranked standing dependency in the KRAS network - present at baseline and independent of a tumor's KRAS dependency. Because the two are nominated by different data and are not positively co-regulated, they argue for a multi-arm KRAS-combination trial that tests each as a separate hypothesis - and they explain why the earlier single-agent Src trials, run without a KRAS backbone and in the wrong disease setting, were not positioned to detect either. The findings are computational nominations that require experimental validation.
A number of intriguing phenomena, including exciton condensation, orbital ordering, and emergence of chirality, have been proposed to accompany charge-density-wave (CDW) formation in the layered transition metal dichalcogenide 1T-TiSe_{2}. Explaining these effects relies on knowledge of the atomic displacement pattern underlying the CDW, yet structural proposals based on spatially averaging bulk crystal diffraction and surface-dependent scanning tunneling microscopy have remained inconsistent. Here, we revisit the CDW superlattice structure of 1T-TiSe_{2} with selected-area electron diffraction, a bulk-sensitive probe capable of capturing submicrometer spatial variations while maintaining high momentum resolution. We observed superlattice peak extinction rules that are incompatible with previously reported atomic displacement patterns, and we found two categories of CDW phases characterized by distinct interlayer orderings. Our analysis identifies a set of possible superlattice structures consistent with the extinction rules, all featuring a one-dimensional displacement pattern for each atomic type and possessing a large number of nearly degenerate CDW domains. These findings shed light on the longstanding discrepancy in the low-temperature space group of 1T-TiSe_{2} and provide a new basis for understanding the gyrotropic electronic order and metastability in this material. Our results further underscore the importance of bulk-sensitive mesoscopic techniques in investigating materials that host unconventional superlattices.