Biology subjects

Levin, S.

Publications and source records attributed to Levin, S..

13 recordsLinked to original sources

bioRxiv2026

Defective Viral Genomes Reveal History-dependent Self-regulation of Type I Interferon Dynamics

Type I interferons (IFN) help clear a viral infection, but IFN levels can then decline to reset the antiviral state and avoid innate immune dysregulation. Such dysregulation can occur following infection with highly pathogenic and pandemic RNA viruses, such as H5N1 influenza A viruses or SARS-CoV-2. In spite of the strong innate immune response that these viruses induce, pandemic viruses replicate and spread successfully, suggesting that they can circumvent the effects of IFN. Innate immune activation is triggered when host cells detect viral RNA, especially defective viral genomes (DVGs). A strong IFN response (e.g. to DVGs or a highly immunogenic wild-type infection) must then decline through negative feedback involving the IFN receptor. How DVGs modulate this feedback remains poorly understood. To quantify positive and negative IFN regulation, we first performed in vitro experiments combining different doses of viral RNA and exogenous IFN, and measured subsequent IFN expression. We next developed an in vivo Bayesian computational model that captures the impact of influenza virus DVGs on both positive and negative IFN feedback. Competition between DVGs and virus is also considered. Finally, we calibrated this model on published in vitro and in vivo influenza virus infection data. Our model suggests that the cumulative IFN exposure of a host cell, rather than the instantaneous IFN level, shapes further IFN induction; this gives DVGs a dual role: beyond triggering IFN induction, they can also lower it through negative feedback. Our model further predicts that these effects are important locally, shaping the spatial dynamics of the response, allowing suppression of innate immune responses in neighbouring, uninfected cells. Through this model, we can explain two important biological observations: i) IFN levels can decline while virus and DVG levels continue to rise in tissue culture and mouse infections; and ii) pandemic viruses that produce high levels of immunogenic RNA molecules can successfully replicate through local innate immune suppression. Overall, we propose that heterogeneity within viral populations (including DVGs and other noncanonical viral RNAs) can modulate positive and negative feedback loops and shape infection outcomes. More broadly, our work may support studies into the therapeutic use of these viral RNA populations.

microbiology↗

bioRxiv2026

Noise and determinism in Trinidadian guppy population dynamics

Natural populations are often nonlinear and exhibit substantial variability. A central question is how stochasticity interacts with density-dependent regulation to shape population stability. We address this using four long-term time series of Trinidadian guppies and find that their dynamics are well described by a stochastic logistic model with multiplicative environmental noise. The model predicts that stochasticity does not merely add fluctuations around deterministic carrying capacity, but alters the equilibrium structure. Using stochastic bifurcation theory, we show that increasing noise shifts the most-probable population size below the deterministic equilibrium and can push populations closer to a noise-induced bifurcation, even when mean growth rates remain positive. The effects of stochasticity across populations align with known ecological differences among streams, particularly the effects of light level and seasonality. The analysis also identifies populations most sensitive to perturbations, which are not detected by standard early warning indicators. Temporal and spectral analyses further show that intrinsic growth rate governs local recovery, while seasonal variation interacts with density-dependence to shape longer-term population fluctuations. Together, our results show that stochasticity can alter resilience and vulnerability by reshaping ecological stability landscapes.

ecology↗

bioRxiv2026

SIZE DETERMINATION AND MULTIPLEXED FLUORESCENCE-BASED PHENOTYPING OF SINGLE CELL-DERIVED MEMBRANE VESICLES USING A NANOFLUIDIC DEVICE

Extracellular vesicles (EVs) are cell-secreted biological nanoparticles that play a crucial role in intercellular communication and are gaining increasing attention as diagnostic biomarkers, therapeutic agents, and drug delivery vehicles. Consequently, the development of robust and sensitive methods for their characterization is essential. Herein we present the use of a microscope-mounted nanofluidic device for direct size determination and multi-parametric (3-color) fluorescence-based phenotyping of single biological nanoparticles that are in the size range of 20-200 nm in a method we denote Nano-SMF (SMF; size and multiplexed fluorescence). We demonstrate that it is possible to accurately determine the size of nanoparticles by analyzing their one-dimensional Brownian motion during directional flow through nanochannels, achieving size distributions for monodisperse nanoparticle solutions that are on par with TEM analysis, and size discrimination of nanoparticle mixtures that is significantly improved compared to conventional nanoparticle tracking analysis (NTA). Furter, we demonstrate that the method can be applied to analyze EVs directly in minute volumes of cell supernatant, avoiding pre-isolation or concentration steps. The method was applied to phenotype CD63- and CD81-positive EVs from a human embryonic kidney cell model, demonstrating that vesicle sub-populations defined by these two tetraspanin biomarkers differ significantly in size.

biophysics↗

bioRxiv2026

Claustral Input Consolidates Anterior Cingulate Cortical States for Selective Behavior

Efficient behavior depends on consolidating selective strategies that prioritize informative cues and suppress irrelevant signals. Previous studies have implicated the claustrum in coordinating cortical activity and large-scale brain states across behavioral contexts, yet its precise contribution to online behavioral control versus the consolidation of frontal control strategies remains unresolved. Here we combined large-scale Neuropixels recordings with targeted optogenetic perturbation of claustral neurons projecting to the anterior cingulate cortex in behaving mice. During adaptation to altered task context and constraints, frontal cortical activity reorganized into a coordinated control regime characterized by sharpened encoding of task-relevant cues, suppression of non-instructive signals, structured low-frequency dynamics, and rapid transitions between population-level neural states. Temporally misaligned claustral signaling disrupted this reorganization, selectively impairing the consolidation of efficient, cue-selective strategies across sessions without affecting trial-by-trial task execution. These findings identify a role for the claustrum in shaping frontal dynamics that consolidate adaptive control strategies.

neuroscience↗

bioRxiv2026

Context-dependent reorganization of behavioral strategy during transfer from home-cage to head-fixed performance

Complex behavioral tasks increasingly rely on autonomous training paradigms that enable high-throughput learning in naturalistic settings. Such approaches offer a scalable route for preparing animals for subsequent head-fixed recordings required for high-resolution neural measurements. However, how animals adapt their behavioral strategies across these distinct contexts remains poorly understood. Here, we examine how mice trained autonomously in a group-housed home-cage system reorganize their behavior when transitioned to a head-fixed version of the same delayed-response task. Although overall success rates were comparable across contexts, mice exhibited a striking shift in behavioral policy. Freely behaving home-cage performance was characterized by high engagement and premature responses, whereas head-fixed performance showed a progressive emergence of selective, cue-intensity-dependent responding accompanied by increased omission errors. This selective strategy was strongly associated with improved performance and sustained engagement under head-fixed conditions, reflecting a trade-off between sensitivity to low-intensity cues and suppression of premature actions. Importantly, selectivity did not arise immediately upon head fixation but developed gradually with experience across sessions, indicating learned adaptation rather than a spontaneous response to restraint. Our findings demonstrate that behavioral policy is not solely determined by task rules or sensory demands, but is strongly shaped by task architecture, temporal constraints, and opportunity cost. These results highlight the need to account for context-dependent strategy shifts when interpreting neural activity following transfer from autonomous training to controlled recording environments, and establish a framework for studying adaptive behavior across experimental contexts.

animal behavior and cognition↗

bioRxiv2025

Coupled dynamics of predator group formation and prey populations

1A diverse array of social carnivores, such as orcas and wolves, also hunt cooperatively, but it is not well understood how prey availability feeds back with the size of social carnivore groups. Cooperative hunting may expand predators access to food by allowing them to hunt prey they could not catch alone, but many predator groups are much larger than the group size that would maximize individual food intake. One promising explanation is that if individuals can freely leave and join groups, then predators behaving adaptively should continue to join a group until the fitness that they achieve in the group is the same as that of being solitary. Here, we investigate the stable group sizes that form in a population of predator groups when predators hunt two types of prey: big prey that is best hunted in groups and small prey that is best hunted alone. In conjunction, we track the dynamics of the distribution of predator group sizes when individuals make decisions about whether to join or leave groups based on their own fitness. We find that if individual predators are able to freely leave groups and pair up with other individuals, starting new groups, then group sizes at equilibrium are much smaller than expected, generally staying at or below the size that maximizes individual fitness. Furthermore, accounting for flexible group sizes leads to ecological conditions that are not predicted if predator group sizes are held constant; in some regions of the parameter space, predators partition resources by forming a bimodal distribution of group sizes, and as a result, create situations where an increase in one prey type helps the other prey population grow. This result has applications to management of carnivore-livestock conflict, implying that increasing populations of wild prey may protect livestock.

ecology↗

bioRxiv2025

On the energetic boundaries of trophic systems

Energy is the fundamental currency of life. Every organism requires a minimum intake to meet maintenance needs, and every trophic transfer dissipates part of the energy flow as heat. Classical theory has emphasized lower bounds on supply--the minimum resource level required for consumers to persist--yet the possible upper bounds and their role in limiting food-chain length remain unclear. We develop a thermodynamically grounded framework that reveals a triad of boundaries: (i) consumer thresholds, (ii) a basal protection limit that reframes the paradox of enrichment as a thermodynamic constraint, and (iii) environmental or physiological supply caps. We show that the intersection of these three boundaries determines the exact range of conditions under which a given ecosystem structure can occur, and that within this range trophic configurations arise as the unique solution that maximizes energy flow. As chain length increases, consumer thresholds rise while the basal protection limit falls, causing this range to contract and eventually disappear. Whether this limit is reached depends on the relative position of these two boundaries and the external supply cap. Their crossing defines an energetic ceiling: a thermodynamic bound on food-chain length beyond which no further level can be sustained. Our results show that feasibility conditions are directly shaped by thermodynamic laws, providing a mechanistic explanation for the emergence and limits of trophic systems.

ecology↗

bioRxiv2025

Imbalance in gut microbial interactions as a marker of health and disease

Imbalances in the human gut microbiome (dysbioses) are linked to multiple diseases but remain poorly understood. Current biomarkers to identify dysbiosis are inconsistent and fail to capture the ecological mechanisms differentiating healthy from diseased microbiomes. We propose a general dysbiosis biomarker, inspired by phenomenology observed in a gut-microbiome theoretical model introduced here. The emergent communities show complex interaction networks and two distinct collective states, corresponding to healthy and dysbiotic microbiomes. Our robust metric for dysbiosis, by quantifying the balance between cooperation and competition, differentiates these states in both simulated and real datasets across diverse diseases. Moreover, it reveals that dysbiosis results from a shift toward greater cooperation in the community. Our metric further correlates with disease progression, highlighting its potential as a diagnostic tool.

microbiology↗

bioRxiv2024

Canary Mating Season Songs Move Between Order and Disorder

Many complex behaviors involve sequences of basic motor or vocal elements governed by syntactic rules, which facilitate flexible and adaptive actions. Songbirds that crystallize their repertoire of vocal syllables and transitions allow researchers to build probabilistic models of syntax rules, providing insight into underlying neural mechanisms. However, in many complex behaviors, syntax rules change over time, such as during learning or in response to new environmental and social contexts. In this study, we investigated the songs of canaries, a seasonal songbird species. Canaries learn a repertoire of 30-50 syllable types, produce syllables in repeat phrases, and organize these phrases into sequences with long-range syntactic dependencies. Since canaries are known to adapt their repertoire annually, we recorded their songs during the spring mating season and examined the syntactic properties that determine syllable sequencing. Over days and weeks, we observed changes in syllable usage rates, syllable numbers within phrases, phrase positions in songs, and in the long-range dependencies of phrase transitions. Acoustic features of syllables were also found to shift alongside these syntactic changes. Quantifying the variability of these properties revealed that the observed changes were not random. Most birds exhibited a clear trend of moving between order and disorder in their songs syntactic and acoustic features. Interestingly, this trend varied across individuals; some birds increased their stereotypy and decreased variability across days, while others adopted more disordered and variable song structures. These findings establish canaries as a valuable animal model for studying the neural mechanisms underlying syntax rules in complex motor sequences, their plasticity in social and environmental adaptation, and in implementing individual-specific strategies.

neuroscience↗

bioRxiv2020

Short-lived plants have stronger demographic responses to climate

To mitigate and adapt to climate change, there is an urgent need to synthesize the state of our knowledge on plant responses to climate. The availability of open-access data, combined with our understanding of plant physiology and life history theory provide opportunities to examine quantitative generalizations regarding which biomes and species are most responsive to climate drivers. Here, we synthesized time series of structured population models from 165 populations from 62 plants around the globe to link plant population growth rates to precipitation and temperature drivers. We expected: (1) more pronounced demographic responses to precipitation than temperature, especially in arid biomes; (2) a higher climate sensitivity in short-lived rather than long-lived species; and (3) a stronger response to climate by species that reproduce more frequently. We found that precipitation anomalies have a nearly three-fold larger effect on{lambda} than temperature. Precipitation has substantially more pronounced effects in more arid sites, but large noise makes this relationship non-significant. Species with shorter generation time have much stronger absolute responses to climate anomalies, while the degree of iteroparity does not correlate with population responses to climate. We conclude that key species-level traits can predict plant population responses to climate, and discuss the relevance of this generalization for conservation planning and evolutionary theory.

ecology↗

bioRxiv2019

Global analysis reveals complex demographic responses of mammals to climate change

Approximately 25 % of mammals are threatened globally with extinction, a risk that is amplified under climate change1. Persistence under climate change is determined by the combined effects of climatic factors on multiple demographic rates (survival, development, reproduction), and hence, on population dynamics2. Thus, to quantify which species and places on Earth are most vulnerable to climate-driven extinction, a global understanding of how demographic rates respond to climate is needed3. We synthesise information on such responses in terrestrial mammals, where extensive demographic data are available4. Given the importance of assessing the full spectrum of responses, we focus on studies that quantitatively link climate to multiple demographic rates. We identify 106 such studies, corresponding to 86 mammal species. We reveal a strong mismatch between the locations of demographic studies and the regions and taxa currently recognised as most vulnerable to climate change5,6. Moreover, we show that the effects of climate change on mammals will operate via complex demographic mechanisms: a vast majority of mammal populations display projected increases in some demographic rates but declines in others. Assessments of population viability under climate change therefore need to account for multiple demographic responses. We advocate to prioritise coordinated actions to assess mammal demography holistically for effective conservation worldwide.

ecology↗

bioRxiv2018

Dispersal increases the resilience of tropical savanna and forest distributions

Global change may induce changes in savanna and forest distributions, but the dynamics of these changes remain unclear. Classical biome theory suggests that climate is predictive of biome distributions, such that shifts will be continuous and reversible. This view, however, cannot explain a widely observed mismatch between climate and tree cover, which some argue results from fire-vegetation feedbacks maintaining savanna and forest as bistable states, such that, instead, shifts will be discontinuous and irreversible. This bistable model, however, cannot reproduce the spatial aggregation of biomes. Here, we suggest that both models are limited in that they ignore spatial processes, such as dispersal. We examine the contributions of dispersal to determining savanna and forest distributions using a reaction-diffusion model, comparing results qualitatively to empirical savanna and forest distributions in Africa. The diffusion model induces spatially aggregated distributions, separated by a stable savanna-forest boundary. The equilibrium position of that boundary depends not only on precipitation but also on the curvature of precipitation contours with some history dependence (although less than in the bistable model). This model predicts different dynamics in response to global change: the boundary continuously tracks climate, recovering following disturbances, unless remnant biome patches are too small.

ecology↗

bioRxiv2018

Wolbachia-infected Drosophila prefer cooler temperatures

O_LITemperature plays a fundamental role in the dynamics of host-pathogen interactions.\nC_LIO_LIWolbachia is an endosymbiotic bacteria that infects about 40% of arthropod species, which can affect host behaviour and reproduction. Yet, the effect of Wolbachia on host thermoregulatory behaviour is largely unknown, despite its use in disease vector control programs in thermally variable environments.\nC_LIO_LIHere, we used a thermal gradient to test whether Drosophila melanogaster infected with Wolbachia strain wMelCS exhibit different temperature preferences (Tp) to uninfected flies.\nC_LIO_LIWe found that Wolbachia-infected flies preferred a cooler mean temperature (Tp = 25.06{+/-}0.25{degrees}C) than uninfected flies (Tp = 25.78{+/-}0.24{degrees}C).\nC_LIO_LIThis finding suggests that Wolbachia-infected hosts might seek out cooler microclimates to reduce exposure to and lessen the consequences of high temperatures. This finding has generated hypotheses that will be fruitful in areas of research for exploring the mechanisms by which the change in Tp occurs in this complex and significant host-pathogen-environment interaction.\nC_LI

pathology↗