eLife: latest articles

Geomagnetic and visual cues guide seasonal migratory orientation in the nocturnal fall armyworm, the world’s most invasive insect

hugao@njau.edu.cn (Bo-Ya Gao) — Thu, 16 Apr 2026 00:00:00 +0000

The mechanisms guiding nocturnal insect migration remain poorly understood. Although many species are thought to use the geomagnetic field, the sensory basis of magnetic orientation in insects has yet to be clarified. We developed an indoor experimental system to investigate the integration of geomagnetic and visual cues in the seasonal orientation of a globally distributed pest moth, the fall armyworm (Spodoptera frugiperda), a highly invasive species which in the past decade has colonized almost all potentially habitable regions of the globe. Our results demonstrate that fall armyworms require both geomagnetic and visual cues for accurate migratory orientation, with visual cues being indispensable for magnetic orientation. When visual and geomagnetic cues are placed in conflict, moths become disoriented, although not immediately, indicating that sensory recognition of the conflict requires time to process. We also show that the absence of visual cues leads to a significant loss of flight stability, which likely explains the disruption in orientation. Our findings highlight that visual cues are critical for stable magnetic orientation in the fall armyworm, offering a basis for future investigations of visual-magnetic integration in noctuid migrants.

Global transcription factors analyses reveal hierarchy and synergism of regulatory networks and master virulence regulators in Pseudomonas aeruginosa

xindeng@cityu.edu.hk (Beifang Lu) — Thu, 16 Apr 2026 00:00:00 +0000

The transcription factor (TF) regulatory network in Pseudomonas aeruginosa is complex and involves multiple regulators that respond to various environmental signals and physiological cues by regulating gene expression. However, the biological functions of at least half of its 373 putative TFs remain uncharacterised. Herein, chromatin immunoprecipitation sequencing (ChIP-seq) was used to investigate the binding sites of 172 TFs in the P. aeruginosa PAO1 strain. The results revealed 81,009 significant binding peaks in the genome, more than half of which were located in the promoter regions. To further decode the diverse regulatory relationships among TFs, a hierarchical network was assembled into three levels: top, middle, and bottom. Thirteen ternary regulatory motifs revealed flexible relationships among TFs in small hubs, and a comprehensive co-association atlas was established, showing the enrichment of seven core associated clusters. Twenty-four TFs were identified as the master regulators of virulence-related pathways. The pan-genome analysis revealed the conservation and evolution of TFs in P. aeruginosa complex and other species. A web-based database combining existing and new data from ChIP-seq and the high-throughput systematic evolution of ligands by exponential enrichment was established for searching TF-binding sites. This study provides important insights into the pathogenic mechanisms of P. aeruginosa and related bacteria and is expected to contribute to the development of effective therapies for infectious diseases caused by this pathogen.

Heat shock factor regulation of antimicrobial peptides expression suggests a conserved defense mechanism induced by febrile temperature in arthropods

lsshjg@mail.sysu.edu.cn (Bang Xiao) — Thu, 16 Apr 2026 00:00:00 +0000

Temperature is a critical factor influencing the outbreak and progression of viral diseases in organisms. Febrile temperatures have been shown to enhance immune competence and reduce viral replication in various species. However, the underlying mechanisms remain largely unknown. In this study, we investigate the molecular mechanisms by which elevated temperatures confer resistance to viral infections, focusing on the role of heat shock factor 1 (HSF1) in regulating antimicrobial effectors rather than the traditional target genes molecular chaperones. Using shrimp Litopenaeus vannamei as a model, we demonstrate that febrile temperatures induce HSF1, which in turn upregulates antimicrobial peptides (AMPs) that target viral envelope proteins and inhibit viral replication. Importantly, this is the first to show that HSF1 directly binds to the heat shock element (HSE) motifs of AMPs both in shrimp and Drosophila S2 cells, suggesting this may be a conserved regulatory mechanism in arthropods. Additionally, our findings highlight the role of HSF1 beyond the classical heat shock response, revealing its critical function in modulating innate immunity. These insights provide new avenues for managing viral infections in aquaculture and other settings by leveraging environmental temperature control.

Hidden folds reveal brain organization

jurgen.germann@uhn.ca (Jürgen Germann) — Wed, 15 Apr 2026 00:00:00 +0000

Previously underappreciated folds in the cerebral cortex provide insight into how its structure varies across individuals.

Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors

fx220@cam.ac.uk (Andrea R Tentner) — Wed, 15 Apr 2026 00:00:00 +0000

During neural tube patterning, a gradient of Sonic hedgehog (Shh) signaling specifies ventral progenitor fates. The cellular response to Shh is processed through a genetic regulatory network (GRN) to specify distinct fate decisions. This process integrates Shh response level, duration, and other inputs and is affected by noise in signaling and cell position. How reliably the Shh response profile predicts the fate choice of a single cell remains unclear. Here, we use live imaging to track neural progenitors in developing zebrafish and quantify both Shh and fate reporters in single cells over time. We found that there is significant heterogeneity between Shh response and fate choice in single cells. We quantitatively modeled reporter intensities to obtain single-cell response levels over time and systematically evaluated their correlation with cell fate specification. Motor neuron progenitors (pMNs) exhibit a high degree of variability in their Shh responses, which is particularly prominent in the posterior neural tube where the Shh response dynamics are similar to those of the more ventrally fated lateral floor plate cells (LFPs). Our results highlight the precision limit of morphogen-interpretation GRNs in small and dynamic target cell fields.

TAD boundaries and gene activity are uncoupled

mistelit@mail.nih.gov (Adib Keikhosravi) — Wed, 15 Apr 2026 00:00:00 +0000

Topologically associating domains (TADs) are prominent features of genome organization. A proposed function of TADs is to contribute to gene regulation by promoting chromatin interactions within a TAD and by suppressing interactions between TADs. Here, we directly probe the structure-function relationship of TADs by simultaneously assessing the behavior of TAD boundaries and gene activity at the single-cell and -allele level using high-throughput imaging. We find that while TAD boundaries pair more frequently than non-boundary regions, these interactions are infrequent and are uncorrelated with transcriptional activity of genes within the TAD. Similarly, acute global transcriptional inhibition or gene-specific activation does not alter TAD boundary proximity. Furthermore, while loss of the cohesin component RAD21 alters gene activity, disruption of TAD boundaries by depletion of the architectural chromatin protein CTCF is insufficient to alter expression of genes within the TAD. These results suggest that TAD boundary architecture and gene activity are largely uncoupled.

A lipoprotein partner for the Escherichia coli outer membrane protein TolC

bfl20@cam.ac.uk (Andrzej Harris) — Wed, 15 Apr 2026 00:00:00 +0000

The outer membrane protein TolC from Escherichia coli belongs to an extensive superfamily whose members are found throughout the didermal, Gram-negative bacterial lineages. The protein serves as an activated exit duct in multi-drug efflux pumps and protein secretion machinery. Many TolC homologues bear a lipid modification on the N-terminus that embeds into the inner leaflet of the outer membrane and appears to have been a conserved feature; however, the moiety is absent entirely in the E. coli TolC. We have discovered that the E. coli lipoprotein YbjP interacts extensively with the periplasmic surface of TolC and its N-terminal lipid moiety is embedded in the membrane, mimicking the intramolecular and modification-membrane interactions seen in TolC homologues. Here, we present cryo-EM structures of the MacA-MacB-TolC and AcrA-AcrB-TolC tripartite pumps complexed to YbjP. Although the association occurs spontaneously both in vitro and in vivo, the YbjP-TolC interaction is not required for efflux activity under standard laboratory conditions. YbjP may contribute to stabilising the orientation and distribution of TolC in the outer membrane, as well as the expression of transporters for tryptophan and cyclic peptide toxins.

New idtracker.ai rethinks multi-animal tracking as a representation learning problem to increase accuracy and reduce tracking time

gonzalo.polavieja@neuro.fchampalimaud.org (Gonzalo de Polavieja) — Wed, 15 Apr 2026 00:00:00 +0000

idTracker and idtracker.ai approach multi-animal tracking from video as an image classification problem. For this classification, both rely on segments of video where all animals are visible to extract images and their identity labels. When these segments are too short, tracking can become slow and inaccurate and, if they are absent, tracking is impossible. Here, we introduce a new idtracker.ai that reframes multi-animal tracking as a representation learning problem rather than a classification task. Specifically, we apply contrastive learning to image pairs that, based on video structure, are known to belong to the same or different identities. This approach maps animal images into a representation space where they cluster by animal identity. As a result, the new idtracker.ai eliminates the need for video segments with all animals visible, is more accurate, and tracks up to 700 times faster.

A stress-activated neuronal ensemble in the supramammillary nucleus produces anxiety-like behavior in male mice

jhan2012@snnu.edu.cn (Jing Han) — Wed, 15 Apr 2026 00:00:00 +0000

Anxiety is a prevalent negative emotional state induced by stress; however, the neural mechanism underlying anxiety is still largely unknown. We used acute and chronic stress to induce anxiety and test anxiety-like behavior; immunostaining, multichannel extracellular electrophysiological recording, and Ca²⁺ imaging to evaluate neuronal activity; and virus-based neuronal tracing to label circuits and manipulate circuitry activity. Here, we identified a hypothalamic region, the supramammillary nucleus (SuM), that plays an important role in anxiety-like behavior. We then characterized a small ensemble of stress-activated neurons (SANs) that are recruited by stress. These SANs respond specifically to stress, and their activation robustly increases anxiety-like behavior in male mice. We also found that ventral subiculum (vSub)-SuM projections, but not dorsal subiculum (dSub)-SuM projections, encode anxiety-like behavior and that inhibition of these vSub-SuM projections has an antianxiety effect. These results indicate that the reactivation of stress-activated supramammillary cells and relevant neural circuits is an important neural process underlying anxiety-like behavior.

Epigenetics and chromatin structure regulate var2csa expression and the placental-binding phenotype in Plasmodium falciparum

karine.leroch@ucr.edu (Hannes Hoppe) — Wed, 15 Apr 2026 00:00:00 +0000

Plasmodium falciparum is responsible for what appears to be a never-ending public health issue in the developing world. With repeated infections, a gradual semi-immunity to severe malaria can be acquired, but this is disrupted when women become pregnant as the parasite cytoadheres in the placenta to prevent splenic clearance. This change in tissue tropism is due to specific transcription of the antigenically variable adhesin VAR2CSA. To better understand the molecular mechanisms activating var2csa and antigenic variation overall, we used a combination of phenotypic and systems biology assays. We first established phenotypically homogenous populations of VAR2CSA-expressing and placenta-binding parasites that were shown to exclusively transcribe var2csa while all other var genes remained silenced. We also confirmed that the transcriptional activation was strongly associated with distinct depletion of repressive H3K9me3 marks. Further, we used chromatin conformation capture as a high-resolution approach to determine interchromosomal interactions and established that transcriptional activation is linked to a small yet significant repositioning of var2csa relative to heterochromatic telomeric clusters. Lastly, we demonstrated that occupancy of 5-methylcytosine was present in all var genes but independent of transcriptional repression and switching. All together, these findings provide insights at high resolution into the potential role of 5-methylcytosine in P. falciparum and increase our understanding of the mechanisms regulating antigenic variation at the epigenetics and chromatin structure level.

Endogenous precision of the number sense

arthurpc@fas.harvard.edu (Arthur Prat-Carrabin) — Wed, 15 Apr 2026 00:00:00 +0000

The behavioral variability in psychophysical experiments and the stochasticity of sensory neurons have revealed the inherent imprecision in the brain’s representations of environmental variables. Numerosity studies yield similar results, pointing to an imprecise ‘number sense’ in the brain. If the imprecision in representations reflects an optimal allocation of limited cognitive resources, as suggested by efficient-coding models, then it should depend on the context in which representations are elicited. Through an estimation task and a discrimination task, both involving numerosities, we show that the scale of subjects’ imprecision increases, but sublinearly, with the width of the prior distribution from which numbers are sampled. This sublinear relation is notably different in the two tasks. The double dependence of the imprecision — both on the prior and on the task — is consistent with the optimization of a tradeoff between the expected reward, different for each task, and a resource cost of the encoding neurons’ activity. Comparing the two tasks allows us to clarify the form of the resource constraint. Our results suggest that perceptual noise is endogenously determined, and that the precision of percepts varies both with the context in which they are elicited and with the observer’s objective.

Kinesin-1 conformational dynamics are controlled by a cargo-sensitive TPR switch

jj.phillips@exeter.ac.uk (Christiane Schaffitzel) — Tue, 14 Apr 2026 00:00:00 +0000

Kinesin-1 is a dynamic heterotetrameric assembly of two heavy and two light chains (KHC and KLC) that mediates microtubule-based intracellular transport of many different cargoes. The complex adopts a compact, autoinhibited state that is activated by cargo-adaptor proteins containing specific short linear peptide motifs (SLiMs). These motifs interact with the tetratricopeptide repeat (TPR) domains of the KLCs. The mechanism coupling SLiM recognition to activation-associated conformational changes in the complex is unknown. Here, we combine protein design, computational modelling, biophysical analysis, and electron microscopy to examine the structural and mechanistic consequences of SLiM binding to the KLC-TPR domain within the complete heterotetrameric holoenzyme. We show that coiled coil 1 (CC1) of the KHC docks KLC TPR domains in the autoinhibited complex, forming the ‘shoulder’ feature observed in electron microscopy. Disrupting this interaction or binding an activating SLiM dislocates the TPR shoulder, freeing the motor domains and promoting transition between its closed, inactive, and open states. Opening the kinesin-1 complex facilitates binding to the microtubule-associated kinesin-1 cofactor, microtubule-associated protein 7 (MAP7). Therefore, cargo-mediated dislocation of the TPR shoulder serves as a key initial step in kinesin-1 activation, allosterically linking cargo binding to motor dynamics.

Adaptive variation in avian eggshell gas conductance and structure across elevational gradients?

docampo@princeton.edu (Carlos D Cadena) — Tue, 14 Apr 2026 00:00:00 +0000

Many tropical bird species have restricted elevational distributions, potentially limited by how environmental conditions affect physiological processes. While some studies have examined adult physiology across elevations, relatively little attention has been given to the structure and function of eggshells despite their critical role in regulating gas exchange during the vulnerable embryonic stage. At high elevations, dry air is expected to increase water loss from the egg, and natural selection may favor lower gas conductance to reduce desiccation risk. Structural variation in eggshells, such as increased shell thickness or reduced pore size and density, could serve as a mechanism to regulate gas diffusion. To test for adaptive variation in eggshell traits along elevational gradients, we measured water vapor conductance and used scanning electron microscopy (SEM) to examine eggshell structure in 197 bird species from the Andes. We found that water vapor conductance declined at high elevations across avian communities. However, structural changes in eggshells varied among bird families and did not vary in a predictable way with elevation, suggesting no relationship or divergent adaptive responses to shared selective pressures, particularly in shell thickness, pore density, and pore size. We propose that examining functional and structural eggshell traits can offer insight into species' elevational limits and inform predictions about their responses to climate change.

Revealing global stoichiometry conservation architecture in cells from Raman spectral patterns

kenichiro_kamei@cell.c.u-tokyo.ac.jp (Hidenori Nakaoka) — Tue, 14 Apr 2026 00:00:00 +0000

Cells can adapt to various environments by changing their biomolecular profiles while maintaining physiological homeostasis. What organizational principles in cells enable the simultaneous realization of adaptability and homeostasis? To address this question, we measure Raman scattering light from Escherichia coli cells under diverse conditions, whose spectral patterns convey their comprehensive molecular composition. We reveal that dimension-reduced Raman spectra can predict condition-dependent proteome profiles. Quantitative analysis of the Raman-proteome correspondence characterizes a low-dimensional hierarchical stoichiometry-conserving proteome structure. The network centrality of each gene in the stoichiometry conservation relations correlates with its essentiality and evolutionary conservation, and these correlations are preserved from bacteria to human cells. Furthermore, stoichiometry-conserving core components obey growth law and ensure homeostasis across conditions, whereas peripheral stoichiometry-conserving components enable adaptation to specific conditions. Mathematical analysis reveals that the stoichiometrically constrained architecture is reflected in major changes in Raman spectral patterns. These results uncover coordination of global stoichiometric balance in cells and demonstrate that vibrational spectroscopy can decipher such biological constraints beyond statistical or machine-learning inference of cellular states.

Active regulation of the epidermal growth factor receptor by the membrane bilayer

binz@mit.edu (Bin Zhang) — Tue, 14 Apr 2026 00:00:00 +0000

Cell surface receptors transmit information across the plasma membrane to connect the extracellular environment to intracellular function. While the structures and interactions of the receptors have been long established as mediators of signaling, increasing evidence suggests that the membrane itself plays an active role in both suppressing and enhancing signaling. Identifying and investigating this contribution has been challenging owing to the complex composition of the plasma membrane. We used cell-free expression to incorporate the epidermal growth factor receptor (EGFR) into nanodiscs with defined membrane compositions and characterized ligand-induced transmembrane conformational response and interactions with signaling partners using single-molecule and ensemble fluorescence assays. We observed that both the transmembrane conformational response and interactions with signaling partners are strongly lipid dependent, consistent with previous observations of electrostatic interactions between the anionic lipids and conserved basic residues near the membrane adjacent domain. Strikingly, the active conformation of EGFR and high levels of ATP binding were maintained regardless of ligand binding with high anionic lipid content typical of cancer cells, where EGFR signaling is enhanced. In contrast, the conformational response was suppressed in the presence of cholesterol, providing a mechanism for its known inhibitory effect on EGFR signaling. Our findings introduce a model of EGFR signaling in which the lipid environment can override ligand control, providing a biophysical basis for both robust EGFR activity in healthy cells and aberrant activity under pathological conditions. The membrane-adjacent protein sequence, likely responsible for the lipid dependence, is conserved among receptor tyrosine kinases, suggesting that active regulation by the plasma membrane may be a general feature of this important class of proteins.

Enhanced bacterial chemotaxis in confined microchannels occurs at lane widths matching circular swimming radius

zhchi@ustc.edu.cn (Caijuan Yue) — Tue, 14 Apr 2026 00:00:00 +0000

Understanding bacterial behavior in confined environments is helpful for elucidating microbial ecology and developing strategies to manage bacterial infections. While extensive research has focused on bacterial motility on surfaces and in porous media, chemotaxis in confined spaces remains poorly understood. Here, we investigate the chemotaxis of Escherichia coli within microfluidic lanes under a linear concentration gradient of L-aspartate. We demonstrate that E. coli exhibits significantly enhanced chemotaxis in lanes with sidewalls compared to open surfaces. We attribute this phenomenon primarily to the intrinsic chiral clockwise circular motion of surface-swimming bacteria and the subsequent alignment effect upon collision with the sidewalls. By varying lane widths, we identify that an 8 μm width—approximating the radius of bacterial circular swimming on surfaces—maximizes chemotactic drift velocity. These results are supported by both experimental observations and stochastic simulations, establishing a clear proportional relationship between optimal lane width and the radius of bacterial circular swimming. Further geometric analysis provides an intuitive understanding of this phenomenon. Our results may offer insights into bacterial navigation in complex biological environments such as host tissues and biofilms, providing a preliminary step toward exploring microbial ecology in confined habitats and potential strategies for controlling bacterial infections.

Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens

karamooz@ohsu.edu (Andrew J Olive) — Tue, 14 Apr 2026 00:00:00 +0000

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can be sensed by T cells, which are essential for the control of infection. In comparison to viral infections, Mtb antigens are relatively limited and hence, challenging to sample. Specialized antigen presentation pathways enable the presentation of such scarce antigens to CD8⁺ T cells, which are, thus, uniquely poised to survey intracellular environments. A subset of CD8⁺ T cells prevalent in the airways, known as mucosal-associated invariant T (MAIT) cells, can be activated through the presentation of Mtb antigens via the major histocompatibility complex class I-related protein 1 (MR1) molecule. Prior work demonstrates that endosomal calcium signaling is critical for MR1-mediated presentation of Mtb-derived antigens. Here, we show that the calcium-sensing trafficking proteins Synaptotagmin (Syt) 1 and Syt7 specifically promote MAIT cell activation in response to Mtb-infected cells. In bronchial epithelial cells, Syt1 and Syt7 localize to late endo-lysosomes and MR1 vesicles. Loss of Syt1 and Syt7 results in enlarged MR1 vesicles and an increased number of MR1 vesicles in close proximity to Mtb-containing vacuoles during infection. This study identifies a specialized pathway in which Syt1 and Syt7 facilitate the translocation of MR1 from Mtb-containing vacuoles, potentially to the cell surface for antigen presentation.

Fear conditioning biases olfactory sensory neuron frequencies across generations

bjm2174@columbia.edu (Alexis Kim) — Tue, 14 Apr 2026 00:00:00 +0000

The main olfactory epithelium initiates the process of odor encoding. Recent studies have demonstrated intergenerationally inherited changes in the olfactory system in response to fear conditioning, resulting in increases in olfactory sensory neuron frequencies and altered responses to odors. We investigated changes in the cellular composition of the olfactory epithelium in response to an aversive stimulus. Here, we achieve volumetric cellular resolution to demonstrate that olfactory fear conditioning increases the number of odor-encoding neurons in mice that experience odor-shock conditioning (F0), as well as their unconditioned offspring (F1). We demonstrate that the increase in F0 is due, in part, to the biasing of the stem cell layer of the main olfactory epithelium. A detailed analysis of F1 behavior revealed subtle odor-specific differences between the offspring of unconditioned and conditioned parents, despite the absence of an active aversion to the conditioned odor. Thus, we reveal intergenerational regulation of olfactory epithelium composition in response to olfactory fear conditioning, providing insight into the heritability of acquired phenotypes.

Individuality across environmental context in Drosophila melanogaster

mathias.wernet@fu-berlin.de (Cara Knief) — Mon, 13 Apr 2026 00:00:00 +0000

Animal behavior is individually variable, and this variability is often consistent over time, a phenomenon called individuality or personality when multiple traits are involved. However, most studies test individuality in only one environment, even though behavior is known to be context-dependent. Analogous to the human ‘person-situation debate,’ we asked whether and to what extent behavioral individuality persists across changing environmental situations in Drosophila melanogaster. Using established and new behavioral assays, we examined three individual traits, namely exploration, attention, and anxiety, across varying environmental contexts, including temperature, visual cues, and arena shape, in both walking and flying flies. We found that individuality is strongly context-dependent, but even under substantial environmental changes, at least one behavioral trait retained individual-specific variation. Different environmental features did not affect individuality equally; instead, they formed a hierarchy in their influence on behavioral consistency. This hierarchy was supported by generalized linear modeling and hierarchical linear mixed-model analysis. Our results show that, as in humans, individuality in flies persists across different situations, although less strongly than across repeated tests in the same context. These findings establish Drosophila as a model for dissecting the developmental, neural, and genetic mechanisms underlying consistent individual differences in behavior across variable environments.

Cocaine disrupts hidden states in the brain

rkeiflin@ucsb.edu (Margo Le) — Mon, 13 Apr 2026 00:00:00 +0000

Cocaine use disrupts the encoding of abstract states in the orbitofrontal cortex.

Audiovisual cues must be predictable and win-paired to drive risky choice

brett.hathaway@nih.gov (Angela Langdon) — Mon, 13 Apr 2026 00:00:00 +0000

Risky or maladaptive decision making is thought to be central to the etiology of both drug and gambling addiction. Salient audiovisual cues paired with rewarding outcomes, such as the jackpot sound on a win, can enhance disadvantageous, risky choice in both rats and humans, yet it is unclear which aspects of the cue-reward contingencies drive this effect. Here, we implemented six variants of the rat gambling task (rGT), in which animals can maximize their total sugar pellet profits by avoiding options paired with higher per-trial gains but disproportionately longer and more frequent time-out penalties. When audiovisual cues were delivered concurrently with wins and scaled in salience with reward size, significantly more rats preferred the risky options as compared to the uncued rGT. Similar results were observed when the relationship between reward size and cue complexity was inverted and when cues were delivered concurrently with all outcomes. Conversely, risky choice did not increase when cues occurred randomly on 50% of trials, and decision making actually improved when cues were coincident with losses alone. As such, cues do not increase risky choice by simply elevating arousal or amplifying the difference between wins and losses. It is instead important that the cues are reliably associated with wins; presenting the cues on losing outcomes as well as wins does not diminish their ability to drive risky choice. Computational analyses indicate reductions in the impact of losses on decision making in all rGT variants in which win-paired cues increased risky choice. These results may help us understand how sensory stimulation can increase the addictive nature of gambling and gaming products.

Principles of gamma synchrony predict figure–ground perception in texture stimuli

mario.senden@maastrichtuniversity.nl (Mario Senden) — Fri, 10 Apr 2026 00:00:00 +0000

Gamma synchrony is ubiquitous in visual cortex, but whether it contributes to perceptual grouping remains contentious based on observations that gamma frequency is not consistent across stimulus features and that gamma synchrony depends on distances between image elements. These stimulus dependencies have been argued to challenge the idea that the visual system groups image elements by synchronizing the neural assemblies that encode them. Here, we argue instead that these dependencies may shape synchrony in perceptually meaningful ways. Indeed, according to the theory of weakly coupled oscillators (TWCO), synchrony-based grouping mechanisms require stimulus dependence. Synchronization among coupled oscillators depends on frequency dissimilarity and coupling strength, which in early visual cortex relate to local feature dissimilarity and physical distance, respectively. We manipulated these factors in a texture segregation experiment wherein human observers identified the orientation of a figure defined by reduced contrast heterogeneity compared to the background. Human performance followed TWCO predictions both qualitatively and quantitatively, as formalized in a computational model. Moreover, we found that when enriched with a Hebbian learning rule, our model also predicted human learning effects: Increases in model gamma synchrony due to perceptual learning predicted improvements in texture segregation across sessions. Taken together, our data suggest that the stimulus-dependence of gamma synchrony captures local image statistics and is linked to the stimulus-dependence of texture segregation, and that the effect of visual experience on gamma synchrony provides a viable perceptual learning mechanism for training-induced improvements in texture segregation. Our results suggest that gamma synchrony with its inherent stimulus dependencies can provide a plausible mechanistic basis for perceptual grouping and visual scene segmentation.

Stimulus dependencies—rather than next-word prediction—can explain pre-onset brain encoding in naturalistic listening designs

ines.schoenmann@gmail.com (Floris P de Lange) — Fri, 10 Apr 2026 00:00:00 +0000

The human brain is thought to constantly predict future words during language processing. Recently, a new approach emerged that aims to capture neural prediction directly by using vector representations of words (embeddings) to predict brain activity prior to word onset. Two findings have been proposed as hallmarks of neural next-word prediction: (i) significant encoding prior to word onset and (ii) its modulation by word predictability. However, natural language is rife with temporal correlations, where upcoming words share statistical information with preceding ones. This raises a critical question: Do these hallmarks emerge from the brain actively predicting future content, or might they be equally well explained by the regression model exploiting these inherent stimulus dependencies? To distinguish between these alternatives, we applied the same encoding analysis to passive control systems, i.e., representational systems that encode the stimulus but cannot predict upcoming words. We show that both hallmarks emerge in two such control systems, namely in word embeddings themselves and in speech acoustics. We further show that proposed methods to correct for these dependencies are insufficient, as the effects persist even after such corrections. Together, these results suggest that pre-onset prediction of brain activity might reflect dependencies in natural language rather than predictive computations. This questions the extent to which this new encoding-based method can be used to study prediction in the brain.

Loss of ZNRF3/RNF43 unleashes EGFR in cancer

fy2111@nyu.edu (Amy T Ku) — Fri, 10 Apr 2026 00:00:00 +0000

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of ZNRF3/RNF43 stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data suggest ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptors, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.

GTPase-activating protein DLC1 spatio-temporally regulates Rho signaling

olivier.pertz@unibe.ch (Giliane Rochat) — Fri, 10 Apr 2026 00:00:00 +0000

Emerging evidence suggests that Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) bind to the cytoskeleton or focal adhesions (FAs), controlling spatio-temporal Rho GTPase activity through feedback mechanisms. We explore such feedback in the Rho-specific GAP Deleted in Liver Cancer 1 (DLC1), which binds to FAs through mechanosensitive interactions. Using a FRET biosensor, we show that DLC1 loss of function leads to globally increased Rho activity and contractility in fibroblasts. Although Rho activity appears macroscopically steady, individual molecules undergo ‘signaling flux’—a dynamic cycle of activation and deactivation. To measure this flux, we built a genetic circuit that enables both optogenetic activation of Rho and simultaneous readout of Rho activity. In cells at mechanical steady state, this reveals that DLC1 globally controls the rate of Rho deactivation, both at FAs and at the plasma membrane. Transient induction of local contractility, however, shows DLC1 associating with and dissociating from FAs during their reinforcement and relaxation, which might provide local positive feedback on Rho activity for robust FA disassembly. Together, our results indicate that DLC1 regulates Rho activity both globally at steady state and locally at FAs under tension, highlighting the complexity of spatio-temporal Rho GTPase signaling.

Contrasting roles for IKK-regulated inflammatory signalling pathways for development and maintenance of type 1 and adaptive γδ T cells

icarvalho@virtus-rr.com (Benedict Seddon) — Fri, 10 Apr 2026 00:00:00 +0000

The inhibitor of kappa-B kinase (IKK) complex is a critical regulator of cell death and inflammatory signalling in multiple cell types. Phosphorylation of IκB proteins by IKK results in their degradation and consequent activation of NF-κB transcription factors. RIPK1, a critical cell death regulator, is also a direct target of IKK kinase activity, thereby repressing its cell death activity. In αβ T cells, the RIPK1 kinase activity of IKK is critical for normal thymic development while mature αβ T cells require IKK for both activation of NF-κB dependent survival programmes and repression of RIPK1. γδ T cells play a unique and versatile role in host immunity with specific effector functions that enable them to act as early responders in immune defence. The role of IKK-regulated pathways in their development and survival is not known. Here, we dissect the function of IKK and downstream pathways for normal γδ T cell homeostasis. We find that IKK is critical to establish replete γδ T cell populations, but that mechanism varys between different subsets. Type 1 γδ T cells require IKK-dependent NF-κB activation for their generation, while IKK is redundant for development of adaptive γδ T cells. Instead, IKK-dependent NF-κB activation is required for their long-term survival. We also find evidence that IKK repression of RIPK1 is required for survival of peripheral but not thymic γδ T cells. Ablation of CASPASE8 did not rescue γδ T cells in the absence of IKK but rather revealed a potent sensitivity of all γδ subsets to necroptosis, which was rescued by kinase-dead RIPK1. Overall, we reveal critical requirements for IKK-regulated inflammatory pathways by γδ T cells that contrast with those of αβ T cells, and between different subsets, highlighting the complexity of the regulation of these pathways in the adaptive immune system.

Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain

arkady.khoutorsky@mcgill.ca (Arkady Khoutorsky) — Fri, 10 Apr 2026 00:00:00 +0000

Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that, in mice, changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell type-specific profiling revealed that spinal inhibitory and excitatory neurons exhibited substantial changes in translation after peripheral nerve injury. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV⁺) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV⁺ neurons decreased their intrinsic excitability and spiking activity. Conversely, reducing translation in spinal PV⁺ neurons prevented the nerve injury-induced decrease in excitability but did not alleviate mechanical hypersensitivity. Together, these findings advance our understanding of translational control mechanisms in the spinal cord during neuropathic pain and highlight their cell type- and phase-specific contributions to gene expression and pain hypersensitivity.

The dominance of large-scale phase dynamics in human cortex, from delta to gamma

david.murray.alexander@gmail.com (David M Alexander) — Thu, 09 Apr 2026 00:00:00 +0000

The organization of the phase of electrical activity in the cortex is critical to inter-site communication, but the balance of this communication across large-scale (>8 cm), macroscopic (>1 cm), and mesoscopic (1 cm to 1 mm) ranges is an open question. The spatial frequencies (i.e. the spatial scales) of cortical waves have been characterized in the gray matter for micro- and mesoscopic scales of cortex and show decreasing spatial power with increasing spatial frequency. This research, however, has been limited by the size of the measurement array, thus excluding large-scale traveling waves. Obversely, poor spatial resolution of extracranial measurements prevents incontrovertible large-scale estimates of spatial power. We estimate the spatial frequency spectrum of phase dynamics in order to quantify the uncertain large-scale range, utilizing stereotactic electroencephalogram to measure local-field potentials within the gray matter. We take advantage of the large extent of spatial coverage of the cortical sheet, and irregular sampling is offset by use of linear algebra techniques. We find the spatial power of the phase is highest at the lowest spatial frequencies (longest wavelengths), consistent with the power spectra ranges for micro- and meso-scale dynamics, but here shown up to the size of the measurement array (up to 8–16 cm). This result arises across a wide range of temporal frequencies, from the delta band (1–3 Hz) through to the high gamma range (60–100 Hz).