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Structure-Constrained Intrinsic Timescales Across Tasks

Intrinsic neural timescale (INT) quantifies the persistence of spontaneous neural dynamics and offers a principled metric for characterizing brain-wide temporal organization. Although a hierarchy of INTs has been established during rest, how task engagement reconfigures this organization and how it is constrained by the structural connectome (SC) remain poorly understood. Here, we systematically mapped whole-brain INT using high-resolution fMRI data from the Human Connectome Project during rest and seven tasks spanning working memory, gambling, motor, language, social, relational, and emotion domains. Task engagement induced robust, regionally heterogeneous changes in INT while largely preserving the brain-wide temporal hierarchy across cognitive states. SC-INT coupling remained strong but consistently decreased during tasks, indicating that anatomical architecture continues to constrain INT, although its influence is attenuated under task demands. To investigate these findings mechanistically, we employed a multiscale, whole-brain neuronal-network model, which revealed that INT increase and peak within a broad critical-like regime. Strong SC-INT coupling, as observed empirically, emerged in the subcritical regime, weakened progressively with increasing network excitability, and reversed in the supercritical regime. These results demonstrate that task engagement reconfigures INTs while maintaining their hierarchical organization, suggesting that both resting and task states operate largely within a common subcritical dynamical regime.

neuroscience

Immunizing small cell lung cancer mice with isoaspartylated Elavl4 after chemotherapy mimics improved survival of anti-ELAVL4 antibody-positive small cell lung cancer patients

Introduction: Small cell lung cancer (SCLC) patients have an ~8% 5-year survival; new therapies are urgently needed. Approximately 15% of SCLC patients have naturally-occurring low-titer antibodies against neuronal ELAVL proteins, associated with improved response to therapy and significantly improved survival. We previously determined that the anti-ELAVL4 response is triggered by isoaspartylation in the unstructured ELAVL4 N-terminal region. Methods: We used a Tp53fl/fl;Rb1fl/fl inducible SCLC mouse model to test whether 1) immunization with isoaspartylated Elavl4 (isoAsp-Elavl4) prior to SCLC induction improves survival in the absence of any other treatment, and 2) immunization with isoAsp-Elavl4 following completion of 3 rounds of cisplatin+etoposide therapy improves survival. Immunizations contained incomplete Freund's adjuvant with either a recombinant N-terminal fragment of Elavl4 (amino acids 1-117), incubated under isoaspartyl-inducing conditions, or phosphate-buffered saline (used as the negative control, since Elavl4 spontaneously isoaspartylates). Mice were monitored by blinded assessors until euthanasia was indicated. Results: IsoAsp-Elavl4-immunized animals all became immune responsive, and spontaneous anti-isoAsp-Elavl4 antibodies were observed in 7% of the control animals. Kaplan-Meier analyses revealed that pre-SCLC immunization with isoAsp-ELAVL4 in the absence of other treatments did not affect survival. In contrast, immunization of SCLC mice following chemotherapy significantly improved survival. Conclusions: An anti-isoAsp-ELAVL4 response can be actively induced in mice and significantly increases SCLC survival when given following chemotherapy. This indicates that the anti-isoAsp-ELAVL4 immune response can be leveraged to develop new therapies for SCLC patients.

cancer biology

Anxiety-Related Traits Are Associated with Subjective Biases but not Altered Threat-Safety Discrimination

Anxiety-related traits (ARTs) have been linked to altered fear learning, but previous studies have typically examined different experimental phases and response systems, limiting the comparability of findings and the accumulation of consistent evidence. Here, we comprehensively examined associations between ARTs and fear conditioning across acquisition, extinction and renewal and across subjective, physiological and neural response systems in a well-powered sample (N = 267) using a two-day differential conditioning paradigm. ARTs were operationalized as a composite of trait anxiety, neuroticism, and intolerance of uncertainty and conditioned responding was assessed using skin conductance responses, fear-potentiated startle, US expectancy ratings, fear ratings, and functional magnetic resonance imaging. Higher ARTs were consistently associated with elevated subjective fear and US expectancy to both threat and safety cues during extinction and renewal, without corresponding elevations in physiological responding. At the same time, ARTs were not associated with threat-safety discrimination in subjective or physiological measures across phases, while neural associations were limited to reduced dorsal anterior cingulate cortex discrimination during early renewal. These findings suggest that ARTs are characterized by a CS unspecific cognitive bias toward heightened threat expectancy and evaluation rather than altered associative fear learning, highlighting the importance of distinguishing conditioned discrimination from general levels of responding across response systems.

neuroscience

XpBrew and PanXpresso - automatic RNA-seq processing workflow and comprehensive collection of gene expression data

Rapid developments in sequencing technologies have reduced the costs of transcriptomic experiments and resulted in a plethora of publicly available RNA-seq datasets. This is a valuable resource that can be harnessed to obtain novel biological insights through data upcycling. In this wake, we introduce XpBrew, an end-to-end Python workflow that was applied to generate PanXpresso, a comprehensive collection of gene expression datasets covering the taxonomic breadth of plants, animals, fungi, bacteria and archaea. XpBrew (https://github.com/PuckerLab/XpBrew) and PanXpresso (https://doi.org/10.60507/FK2/OBIGQH) are freely available.

bioinformatics

A transcriptomic and spatial map of serotonin autoreceptor expression in Drosophila

Serotonin is an evolutionarily ancient neurotransmitter that modulates an array of behaviors such as mood, sleep, and appetite across species. Serotonin acts primarily by binding to serotonin receptors, which are expressed in post-synaptic neurons (heteroreceptors) and serotonergic neurons themselves (autoreceptors). Serotonin autoreceptors modulate serotonergic tone, the foundational principles of which have been excellently demonstrated in vertebrate and invertebrate models. However, many aspects of the mechanisms and contexts in which this modulation occurs are still unclear. Drosophila melanogaster is a powerful model organism that can provide unique insights into autoreceptor function by the ability to perform precise spatial and temporal genetic manipulation with structural and functional readouts / behaviors of serotonin systems. However, a systematic characterization of serotonin autoreceptor expression in Drosophila has not been conducted. Here we use single-cell sequencing and genetic labeling to show that all five serotonin receptors are expressed in serotonergic neurons and map their expression at both the larval and adult stages of development. This is the first evidence of 5-HT2A and 5-HT7 expression in serotonergic neurons in any organism. Moreover, the unique combinations of autoreceptor expression in specific neuronal clusters will aid in the development of novel hypotheses for autoreceptor function, and demonstrates the utility of Drosophila as a model organism to study the function of serotonin autoreceptors.

neuroscience

Time-averaged and Time-varying Structure of the Gastric Network Revealed Through fMRI-Electrogastrogram Synchronization

The gastric network, comprised of brain regions whose activity synchronizes with the stomach's slow-wave rhythm, offers a unique window into the brain-body interaction involved in interoceptive processing. While previous work has established the existence of this network, its intrinsic organization and temporal unfolding remain poorly understood. Here, we reanalyzed resting-state fMRI-electrogastrogram data from 43 healthy adults of both sexes to characterize the time-averaged architecture and time-varying reconfiguration of the gastric network. We identified regions exhibiting phase-locked synchronization with the stomach slow electrical rhythm (0.05 Hz) and characterized cortical parcels comprising this network. Time-averaged graph-theoretical analysis revealed a fixed unimodal organization of functional communities, with primary visual, default mode network (DMN) and dorsal attention regions emerging as the principal time-averaged hubs. Next, we applied edge-centric functional connectivity (eFC) to capture the network state during transient high-amplitude "bursts". Time-varying community detection revealed communities whose compositions formed integrative combinations of DMN, visual, attentional and control elements. Edge-derived hubs shifted away from primary visual dominancy in the time-averaged analysis, and were instead directed by DMN regions, suggesting that moments of heightened connectivity in the network are coordinated by multisensory integration rather than passive sensory processing. These findings demonstrate that the gastric network is not merely a time-averaged, sensory-bound system, but rather a flexible and dynamically reconfiguring interoceptive network whose organization is selectively coordinated by transient cofluctuation events. This work provides a comprehensive network analysis of gastric-brain coupling and reveals a temporally structured mode of interoceptive integration that may support adaptive physiological and cognitive regulation.

neuroscience

Beyond Equilibrium Ensembles: Time Rescaling in Coarse-Grained Simulations across Single-Molecule and Condensate Regimes

Residue-level coarse-grained simulations provide a powerful route for modeling biomolecular condensates over length and time scales that are difficult to access with atomistic molecular dynamics. Coarse-grained models have been shown to reproduce many aspects of equilibrium phase behavior. However, it remains unclear to what extent such models can reproduce the relative timescales of molecular dynamics. Here, we examine this question for complex coacervates with markedly different dynamics, formed by the highly acidic intrinsically disordered protein prothymosin with four cationic partners: linker histone H1, protamine, polylysine, and polyarginine. Coexistence simulations using a residue-level coarse-grained model reproduce key equilibrium observables from experiments, including dense-phase concentrations, ionic-strength-dependent phase behavior, and chain dimensions in the dense and dilute phases. Dynamics are accelerated in these simulations, but a composition-specific time-rescaling factor captures the ionic-strength dependence of chain reconfiguration times within a given complex coacervate. In contrast, time rescaling is not transferable between dense and dilute phases or across condensate compositions and can depend on the chosen observable. These results show that agreement with measured equilibrium observables does not imply a universally transferable timescale for conformational dynamics in residue-level coarse-grained simulations. However, we find that the required time rescaling strongly correlates with the interaction energy of the protein chains, suggesting that the missing frictional effects arise from protein-protein interactions rather than solely from protein-solvent interactions, reminiscent of internal friction. Our findings highlight the need to combine thermodynamic validation with kinetic calibration when interpreting chain relaxation, molecular diffusion, and material properties from residue-level coarse-grained simulations of biomolecular condensates.

biophysics

Resolving Heterogeneous Mechanical Domains via Physics-Aware Deep Clustering of Single-Molecule Force Spectroscopy Data

Many biological processes rely on mechanical forces, with protein molecules acting as key mediators. Understanding how proteins respond to mechanical stress is essential for conditions including cardiomyopathy and muscular dystrophy. Natural proteins such as dystrophin and utrophin are composed of heterogeneous folding domains with distinct mechanical properties; deciphering domain-level behavior provides insights into disease mechanisms and informs therapeutic strategies. Single-molecule force spectroscopy (SMFS) enables probing the mechanical properties of entire proteins, yet current approaches struggle to identify heterogeneous folding domains, particularly without prior knowledge. Here, we present the first automated framework to identify heterogeneous folding domains in SMFS data, applying both existing clustering methods and a novel physics-aware deep clustering architecture, LatentUnfold. LatentUnfold learns complementary latent representations from force magnitude and the force-extension physical relationship through dual autoencoders, jointly optimized for clustering assignments. We apply our framework to experimental SMFS data collected from a synthetic two-domain protein (ddFLN4-Titin I27) as well as natural protein constructs of dystrophin and utrophin, with Monte Carlo simulated datasets serving as controlled validation. For the synthetic protein, we recover mechanical properties consistent with previously reported values for each domain. For the natural proteins, we uncover two mechanically distinct domain populations - corresponding to the N-terminal domain and spectrin-like repeats - with differences in both unfolding force and contour length increase, and reveal different unfolding order between them for the first time. This work enables domain-level biological inference, overcoming prior limitations that relied on averaging and overlooked heterogeneity, thus advancing the understanding of mechanical behavior in protein unfolding.

biophysics

Linoleic Acid-Lyso PG Axis promoting lipid droplet-mitochondria tethering by stabilizing Noncanonically Mitochondrial PPAR β/δ to Ameliorate Microglial Dysfunction in subarachnoid hemorrhage

Background Microglial lipid handling and mitochondrial failure contribute to brain injury after subarachnoid hemorrhage (SAH), but the lipid signals coupling these processes remain unclear. We investigated whether linoleic acid (LA) restores microglial homeostasis through lysophosphatidylglycerol 16:0 (LPG[16:0]) and peroxisome proliferator-activated receptor-{delta} (PPAR{delta}). Methods Cerebrospinal fluid metabolomics included 30 patients with aneurysmal SAH and 10 control participants. Mechanisms were examined in a blood-injection mouse model and hemoglobin-exposed primary mouse microglia using targeted lipidomics, RNA sequencing, mitochondrial and phagocytosis assays, pharmacological perturbation, fractionation, coimmunoprecipitation, thermal shift analysis, and structural modeling. Behavioral outcomes were evaluated by open-field, Y-maze, and Morris water-maze testing. Results; CSF LA was higher in SAH and discriminated the groups within this cohort (area under the curve, 0.9967 [95% CI, 0.9859-1.000]; P<0.001). LA attenuated inflammatory activation and restored phagocytosis, mitochondrial membrane potential, respiration, and ATP production in hemoglobin-exposed microglia. LA restored PLA2G15-associated LPG(16:0), which phenocopied these effects. Transcriptomic and inhibitor analyses identified PPAR{delta} as a downstream effector. LPG(16:0) increased PPAR{delta} stability, and fractionation and protease protection identified a PPAR{delta} pool on the cytosolic face of the outer mitochondrial membrane. PPAR{delta} associated with PLIN2 and CPT1A, promoted lipid droplet-mitochondria apposition, and supported fatty acid oxidation. In mice, LA reduced neuroinflammatory injury and partially improved anxiety-related behavior and spatial memory.

neuroscience

HDAC6 is a novel regulator of endothelial-to-mesenchymal transition in venous thrombosis

Background: Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent disease associated with thrombus formation and vein wall remodeling. Hence, fibrosis might result from endothelial-to-mesenchymal transition (EndMT), characterized by the loss of endothelial markers and the acquisition of mesenchymal markers. In chronic thromboembolic pulmonary hypertension, transforming growth factor (TGF{beta}), the most potent inducer of EndMT, impairs thrombus resolution. However, the molecular mechanisms implicated in TGF[beta] signaling in the context of VTE are unknown. We hypothesized that epigenetic processes regulate the TGF{beta} signaling pathway in endothelial cells promoting EndMT and vascular fibrosis. Aims: To determine if the histone deacetylase 6 (HDAC6) regulates the TGF{beta} signaling pathway in endothelial cells promoting EndMT and delays venous thrombosis. Methods: To study the role of HDAC6 in EndMT, endothelial cells were treated with a pharmacological inhibitor (TCS20b) and incubated with TGF{beta} and thrombin for 2, 3, and 5 days. Real time PCR and Western blot were performed to analyze endothelial and mesenchymal marker expression and TGF{beta} signaling. An experimental model of VTE was used to study the role of HDAC6 on thrombus size overtime. Animals were treated or not with a specific HDAC6 inhibitor (tubastatin A) for 7 to 21 days. Analysis of RNAseq data sets publicly available were used to confirm our main results. Within group and treatment differences were analyzed using two-way ANOVA and Tukeys multiple comparisons. Results: Expression of the mesenchymal markers, calponin and transgelin, was increased by TGF{beta} and thrombin. Interestingly these changes were inhibited in presence of TCS20b. TGF{beta} mediated these effects through ERK1/2 and HDAC6 activation. Inhibition of HDAC6 in vivo reduced thrombus size 7 days after surgery compared to controls. This was associated with reduced expression of the EndMT marker transgelin in endothelial cells compared to the control animals. We found that FN1-EDA expression was associated with EndMT and regulated by HDAC6 in vitro. This marker was also associated with thrombosis in the RNAseq data set that we analyzed and potentially in patients with recurrent DVT. Conclusion: We found that HDAC6 regulates EndMT in venous thrombosis and impairs thrombus resolution. HDAC6 also regulates expression FN1-EDA that appears to be a strong marker associated with DVT and DVT recurrence. Thus, HDAC6 might represent an attractive therapeutic target for patients with a high risk of recurrent VTE.

physiology

Hypothermic Conditions Impair GnRH Pulse Generator Activity and Gametogenesis

Mammalian reproductive function is driven by arcuate kisspeptin neurons, pacemakers of gonadotropin secretion. During energy shortages, animals reallocate resources from reproduction to survival; however, the underlying neural mechanisms remain elusive. Here we used fiber photometry to chronically monitor synchronized episodes of arcuate kisspeptin neuron activity (SEskiss) in adult mice under various energy-saving conditions. In both sexes, SEskiss frequency was markedly suppressed during fasting-induced torpor and pharmacologically induced hypothermia, whereas hypometabolism alone had no discernible effect. A Q neuron-induced hypothermic state (QIH) robustly suppressed SEskiss, leading to impaired gamete maturation, whereas warming the body temperature during QIH fully restored SEskiss frequency. These findings demonstrate that hypothermia, rather than hypometabolism, is the primary driver of suppression of the hypothalamic reproductive axis during energy-saving conditions. This study provides insights into how thermal signals act as critical gatekeepers in the mammalian reproductive system.

neuroscience

Comparison of evolutionary rescue via biological and cultural evolution

Rapid evolution allows populations to persist in environments where they would otherwise go extinct. This phenomenon, known as evolutionary rescue, is typically studied in the framework of biological evolution, yet adaptive traits can also arise and spread through cultural evolution. The present study developed a stochastic eco-evolutionary model to compare rescue probabilities through biological and cultural evolution. Transmission bias governed the rescue probability under cultural evolution by setting how readily a rare adaptive trait was copied. Conformity bias suppressed population persistence because a rare trait was the least likely to be copied. Content bias toward the adaptive trait enabled evolutionary rescue when social learning was rapid, but it typically yielded a lower rescue probability than biological evolution. Only anticonformity bias, together with a high social learning rate, exceeded the rescue probability of biological evolution by enabling the adaptive trait to be established more rapidly. These results demonstrate that transmission bias alters the demographic consequences of cultural evolution and highlight the importance of transmission processes in evolutionary rescue theory. Understanding how adaptive behaviours are socially transmitted may also improve predictions of animal population persistence and inform conservation efforts in rapidly changing environments.

evolutionary biology

The circadian system is affected by Alzheimers disease independently from amyloid beta deposits

Circadian disruption, notably sleep disturbances, serves as an early indicator of Alzheimers disease (AD), preceding cognitive symptoms like memory loss. The suprachiasmatic nucleus (SCN) governs biological rhythms and receives direct retinal input via melanopsin-expressing retinal ganglion cells (mRGCs) to synchronize with environmental light cycles. The anatomical and functional basis for circadian disruption in AD remains unclear. Here, we explored the multi-level relationships between gene expression, the SCN connectome, and regulations of sleep and circadian rhythms in the APP/PS1 mouse model. The sleep architecture of APP/PS1 mice displayed significantly reduced rapid eye movement sleep (REM), associated with a reduced daily core body temperature amplitude and locomotor hyperactivity. Lastly, APP/PS1 mice showed an impaired response to acute light pulse stimulation and present hyperactivity of mRGCs at a young age and hypoactivity of these cells at older ages. These physiological functions are known to be, at least in part, regulated by the SCN, the main target of mRGCs. We noted several modifications in SCN connectomics using serial blockface electron microscopy (SBEM), including a reduction of the dendro-dendritic chemical synapse (DDCS) network that receives a large part of the retinal input and is thought to be crucial for synchronicity between SCN neurons. In addition, we observed multiple signs of dystrophy, including modifications of the shape of dendrites and cell soma, accumulation of aggregated lysosomes, and swelling of axons. At the same time, we investigated the changes in gene expression using spatial transcriptomics. The SCN presents changes in the expression of genes associated with synapse formation, cell adhesion, and neurite growth. These results suggest that, despite the absence of amyloid plaques in the ventral hypothalamus, the SCN of APP/PS1 mice still undergo profound gene expression changes, impacting connectomics and physiological functions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/744599v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@ceedb0org.highwire.dtl.DTLVardef@156cfaaorg.highwire.dtl.DTLVardef@5bc262org.highwire.dtl.DTLVardef@36df4d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience

Motor planning and execution establish distinct feedforward and feedback motor histories

Movements are systematically affected by the recent motor history. These history effects may be induced either by reused motor plans or from lingering tuning of the previous movements' execution. We dissociated planning and execution using four experimental manipulations across two complementary motor paradigms. We isolated planning by preventing execution with stop signals and mechanical blocks, and execution by moving participants' hand passively using a robot manipulandum. History effects emerged in feedforward movement aspects - reaction time and early movement kinematics - following isolated planning. In contrast, they were absent or markedly reduced for isolated execution. History effects emerged also in late movement aspect that involves sensory feedback during execution - movement accuracy and precision - but only when movements were both planned and executed. Feedforward effects generalized across hands, whereas feedback effects were effector specific. Thus, prior motor planning and execution make distinct and complementary contributions in shaping future motor behavior.

neuroscience

Feature-based valuation and its impairment in people with compulsive and addictive symptoms

Effective decision-making requires evaluating options based on relevant features while reducing attention to those that are not. However, how attention prioritizes one source of information over another during value-based decisions remains unknown. Across 7 experiments, we show that irrelevant features both constructively and destructively interfered with how values are assigned to choice options. When relevant and irrelevant features agreed, choice accuracy and speed were facilitated; when they conflicted, accuracy decreased and choices slowed in proportion to the value of the irrelevant feature. We modeled this interference as a weighted sum of relevant and irrelevant feature values. This model explained individual differences in choice behavior and, critically, tracked psychiatric symptom severity related to substance abuse and obsessive-compulsive disorder. This suggests that these symptoms may, in part, reflect an impaired ability to weigh relevant against irrelevant information when assigning value to choice options - a process we term feature-based valuation.

neuroscience

Scaffold Affinity Tunes Biomolecular Condensate Function

Biomolecular condensates (BMCs) organize cellular biochemistry by concentrating selected molecules into dynamic membrane-free compartments. Yet the molecular parameters that determine not only whether condensates form, but also how they behave and what they do, remain poorly defined. Here we show that scaffold binding affinity (Kd) is a quantitative determinant of condensate phase behavior, internal dynamics and biochemical output. Using a modular SUMO-SIM system in which scaffold valency was held constant while binding affinity was systematically varied, we found that affinity governs the phase boundary, resistance to chemical perturbation, and molecular mobility of condensates in vitro and in human cells. In multicomponent mixtures, the highest-affinity scaffold dominated dense-phase composition and dynamics, revealing a hierarchical rule for condensate organization. Finally, affinity-dependent changes in condensate dynamics translated into tunable enzyme activity, establishing binding energetics as an engineerable parameter for programming condensate biochemistry.

biochemistry

Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila

Prions, once mainly studied for their pathogenic roles, are now gaining recognition as adaptive elements in microbial physiology. Over one-third of wild yeast isolates harbor prion proteins, yet their impact on host-microbe interactions remains poorly characterized. Given the ecological dominance of yeasts in the Drosophila mycobiome, we leveraged the Drosophila melanogaster-Saccharomyces cerevisiae system to investigate how the mycobiome-derived prion, [MRPL10+], modulates host physiology. We show that flies exposed to [MRPL10+] yeast exhibit significantly enhanced cold tolerance and increased locomotor activity. This effect persists with heat-killed yeast and diluted culture, suggesting a stable, potent bioactive factor. Using the genetically diverse Drosophila Global Diversity Lines (GDL), we identified natural variation in responsiveness to [MRPL10+] yeast. Genome-wide association and functional RNAi screening revealed a gut-brain signaling axis involving genes critical for digestion, intercellular communication, transcription regulation, and neural transmission. Notably, serotonin and octopamine pathways were essential for [MRPL10+]-induced changes in cold tolerance and locomotion, implicating neuromodulatory circuits in prion-mediated microbial signaling. Our findings establish a mechanistic link between a fungal prion and host metabolic and neural adaptation. This work provides the first genetic dissection of a prion-mediated host-microbe interaction, laying the groundwork for investigating beneficial prions in complex microbial communities and highlighting a new dimension of the mycobiomes influence on animal physiology.

evolutionary biology

Constraining Palaeogeography and Palaeotides for the Cambrian using cnidarian medusae

The ocean tides influence key Earth system processes at a range of spatial and temporal scales. It is known that the geometry of ocean basins is the leading controller of tidal energetics, so well-constrained palaeogeographic reconstructions and tidal properties for Earths past are imperative when investigating other Earth system processes. Here, we present a novel way to constrain both deep-time tidal model results and reconstructions, by combining palaeoecology with sedimentology. We compare new palaeo-tidal model simulations for the Cambrian period, significant for the early origin and radiation of major animal fauna, to tidal proxies. One of the most abundant soft-bodied organisms preserved during this time are cnidarian medusae (jellyfish). A total of 17 cnidarian medusae localities were obtained through the literature, which had an adequate global distribution and occurred at regular intervals throughout the period of study. In some locations there were also estimates of palaeo-tidal range. Our results show a good agreement between the simulations and proxy data. In the few locations where there is disagreement, it is proposed that the palaeogeographic reconstructions are missing details, e.g., island chains, and our results allow for the palaeogeographic reconstructions to be improved. The proxy method presented is promising and can be applied to other time-periods with different marine fossils, particularly at evolutionary and extinction periods where the marginal marine environment is of importance.

paleontology