Nature

Iron mineralization has profoundly influenced Earths biogeochemical history1,2, yet the specific mechanisms underlying banded iron formation (BIF) remain unresolved3-5. Here we profile the microbiomes of Holocene sediments beneath the Larsen C Ice Shelf (LCIS), Antarctica6-8, through stratigraphic analysis of sedimentary ancient DNA combined with metagenomics. Distinct microbial phases aligned with glacial facies boundaries, with sub-ice shelf communities dominated by chemolithoautotrophs including an uncultured Thermodesulfovibrionia. This bacterium, visualized by fluorescence in situ hybridization and designated Candidatus Mariimomonas ferrooxydans (phylum Nitrospirota), emerged as a keystone taxon with high network centrality. Its genome encodes Cyc2, a fused porin-cytochrome outer membrane protein implicated in Fe(II) oxidation. Heterologous expression of Cyc2 in Escherichia coli confirmed its ability to catalyze iron oxidation, supporting iron precipitation under dark, anoxic conditions. These pristine LCIS sediments, unaltered since the last glacial maximum, provide a modern analogue for synglacial BIFs deposited during Neoproterozoic Snowball Earth events. Our findings deliver direct genomic and functional evidence for chemolithotrophic iron oxidation, challenge phototroph-centric models of BIF genesis, and highlight microbial iron cycling as a recurring force in Earths geochemical evolution. Beyond Earth, these insights inform interpretations of iron deposits on other planetary bodies.

Panarthropod vision exhibits extraordinary morphological and functional diversity, yet the sensory biology of tardigrades--microscopic extremophiles renowned for their resilience--remains poorly understood. In the model tardigrade Hypsibius exemplaris, we uncover an unprecedented expansion of opsin genes, with over 100 paralogs constituting the largest known opsin repertoire in any animal. Paradoxically, the visual system is structurally minimalist: a paired, inverse pigment-cup ocellus embedded within the brain lobes, forming a single-pixel, dual-receptor organ. Integrating genomic, phylogenetic, molecular expression, and ultrastructural analyses, we show that directional vision relies on a single rhabdomeric opsin (He-R-Opsin-V), localized to microvilli of the rhabdomeric cell. A ciliary photoreceptor with a lamellated cilium co-expresses two ciliary opsins (He-C-Opsin-1 and -2), suggesting non-visual light detection. These and other non-visual opsins are differentially expressed in the brain, gut, storage cells, and peripheral tissues, implicating them in circadian regulation, neuromodulation, ecdysis, digestion, and environmental sensing. Crucially, the eye is an internalized epidermal vesicle, not a cerebral derivative, challenging long-standing assumptions about its evolutionary origin. These findings reveal how extreme miniaturization drives sensory system simplification in visual organs while enabling parallel evolutionary innovation in non-visual photoreception. This study establishes a new paradigm for sensory evolution in microscale animals.

To learn effectively, animals must generalize across yet distinguish between related contexts. Generalization relies on low-dimensional neural manifolds found throughout neocortex1-3, which accelerate learning by constraining neural activity to task-relevant axes4,5. Conversely, context separation is attributed to neural expansion layers that can project information into high-dimensional feature spaces6-8, most famously cerebellar granule cells (GrCs)9-11. To investigate the generalization-separation tradeoff, we simultaneously imaged key nodes in the universal cortico-cerebellar pathway12,13--premotor layer 5 pyramidal tract (L5PT) and GrCs--during parallel learning of two distinct skills with shared temporal structure. Rather than expanding the cortical representations, GrCs retained their low-rank encoding of each task. Across contexts, however, despite stable cortico-cerebellar coupling, L5PT activity patterns generalized while GrC patterns temporally remapped. Mechanistically, GrCs used affine transformations that rotated the cortical manifolds apart but preserved their intrinsic low-dimensional geometry. Moreover, GrCs decorrelated cortical trajectories most strongly in expert animals. This reveals a fundamental architectural division of labor: the cortex generates invariant dynamic primitives for smooth generalization, while the cerebellum reconfigures them to drive context-specific output.

Working memory allows primates to reason about complex scenes, yet how the brain maintains multiple objects in memory simultaneously remains unclear. Competing theories propose that objects are stored in discrete slots1,2, represented dynamically through switching3-6, or encoded by weighted combinations of single-object representations7-11. We formalized these hypotheses in terms of their quantitative predictions at the level of single neurons and tested them against densely recorded neural data from the dorsomedial frontal cortex and frontal eye field of monkeys trained to perform a novel multi-object working-memory task. Across cross-validated neural data, a Gain model, where population activity reflects weighted compositions of individual object responses, consistently outperformed Slot and Switching models. Trial-specific gain estimates predicted behavioral errors and reaction times, indicating that these latent weights capture meaningful fluctuations in memory fidelity. All results replicated in an independent dataset with different spatial configurations. Together, our work provides a rigorous framework to adjudicate a longstanding debate about how the frontal cortex retains multiple objects, identifying a weighted-sum representation as the format that best explains the neural data.

Many bacterial defense (immune) systems prevent the entry of foreign DNA by directly recognizing and targeting nucleic acids, effectively blocking all mechanisms of horizontal gene transfer1. However, systems defending specifically against conjugation, a major route for gene dissemination, have heretofore not been reported. We have discovered a novel defense factor, which we name AbjA (Abortive conjugation protein A), that specifically limits successful plasmid conjugation into a recipient bacterium. AbjA interacts directly with and targets the ATPase component TrbE of the Type IV secretion system (T4SS)2,3 to induce cell death; this contrasts with most other defense systems that act at the nucleic acid level. AbjA therefore represents the first member of a new class of bacterial defense factors that trigger what we term abortive conjugation. Previously, recipient bacteria were viewed largely as defenseless against the mechanism of conjugation4-6; our discovery and characterization of AbjA demonstrates that recipient bacteria can block conjugation to limit the transfer (and thus spread) of plasmids. Discovery of this class of defense systems thus has implications for bacterial defense, plasmid evolution, and possible strategic alternatives to rationally target plasmid spread, particularly with respect to virulence and antibiotic resistance.

Neuromodulatory systems, notably basal forebrain cholinergic and midbrain dopaminergic pathways, critically influence reinforcement learning 1-3. However, whether and how they cooperate or compete to jointly control associative learning functions remains unresolved. Here we demonstrate that basal forebrain cholinergic and midbrain dopaminergic projection systems form a coordinated and cross-regulating architecture for encoding prediction errors. Using dual-cell-type optogenetic tagging and real-time neurotransmitter measurements in mice performing a psychometric operant learning task, we simultaneously monitored cholinergic and dopaminergic activity during learning. Dopamine and acetylcholine jointly encoded reward prediction errors synergistically following reward and reward-predicting stimuli. In contrast, aversive outcomes elicited opposite responses in cholinergic neurons and approximately half of dopaminergic neurons. Activity in these two populations exhibited negative trial-by-trial correlations, revealing antagonistic dynamics. Consistently, channelrhodopsin-assisted circuit mapping uncovered a disynaptic inhibitory pathway from cholinergic to dopaminergic neurons. Chemogenetic suppression of cholinergic activity disrupted dopaminergic prediction error signaling, reduced punishment-induced suppression of dopamine release, and impaired learning. These results demonstrate that prediction error signaling is jointly implemented by coordinated interactions between major neuromodulatory systems, challenging the prevailing view of their functional independence and revealing coordinated cross-system interactions as an organizing principle of reinforcement learning, with implications for neuropsychiatric disease 4-6.

Pathogens hijack macrophages by triggering pathological cAMP surges that block phagolysosomal killing--a defect mirrored in phagocytes from refractory colitis. We identify a host-encoded, pathogen-specific surge-protector comprised of a three-protein toggle: The innate sensor NOD2 binds and masks an evolutionarily conserved motif in GIV that activates trimeric-GTPase Gi, enforcing a biphasic surge-to-plunge cAMP-program: early, NOD2*GIV assembly permits a brief, tolerogenic cAMP rise, whereas subsequent GIV*Gi engagement collapses cAMP to drive phagolysosomal fusion and microbial clearance. Structural, biochemical, and ultrastructural analyses reveal how molecular toggling imposes precise spatial and temporal control. Pharmacogenomic perturbations pinpoint cAMP-PKA hyperactivation as the defining lesion in GIV-deficient macrophages. Functional studies in primary macrophages and human gut organoid co-cultures show that toggling the NOD2*GIV*Gi-axis is necessary and sufficient to convert tolerant macrophages into microbicidal machines that preserve mucosal barrier integrity. These findings uncover a druggable cAMP-control pathway with therapeutic promise in colitis. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/715116v1_ufig1.gif" ALT="Figure 1"> View larger version (70K): org.highwire.dtl.DTLVardef@6f7c6corg.highwire.dtl.DTLVardef@151d439org.highwire.dtl.DTLVardef@1441b12org.highwire.dtl.DTLVardef@4d76e3_HPS_FORMAT_FIGEXP M_FIG C_FIG eTOC BlurbPathogens hijack macrophages by inducing cAMP surges that help them evade clearance. Anandachar et al. identify a host "toggle switch" in which NOD2 and G proteins compete for GIV, driving a rapid and robust surge-to-plunge transition in cAMP. This temporal switch limits tolerogenic signaling, restores microbial clearance and barrier integrity, and unveils a targetable host pathway in infection and IBD. HighlightsO_LIPathogens exploit cAMP surges in macrophages to block phagolysosomal killing of microbes C_LIO_LIGIV acts as a molecular "toggle" linking NOD2 sensing to Gi-mediated cAMP control C_LIO_LIStructural and mutagenesis studies reveal mutually exclusive binding of NOD2 and Gi to GIV C_LIO_LIPharmacogenomic perturbations pinpoint PKA, not EPAC, as the critical downstream effector C_LIO_LIOrganoid co-cultures show NOD2-GIV-PKA crosstalk safeguards microbial clearance and gut barrier integrity C_LI

Acoustic communication is widespread among vertebrates and central to social behavior. Yet how brain-wide circuits identify conspecific signals and distinguish acoustic elements with different, often sex-specific social valence remains poorly understood. Here we present the first whole-brain analysis of neuronal responses to conspecific vocalisations in vertebrates, using the transparent fish Danionella cerebrum. Combining volumetric calcium imaging with playbacks probing the stimulus space of the natural sound repertoire, we uncover an unexpectedly early and specialized processing hierarchy: hindbrain nuclei already segregate vocalization-like pulse trains from tones, midbrain regions sharpen these representations and extract temporal features that define vocalization type, and the central posterior thalamic nucleus responds selectively to conspecific vocalization rates and thus acts as a gate for social sounds. Male and female brains share this early feature code but diverge in diencephalic and telencephalic regions, where identical acoustic features evoke sex-specific population activity patterns that parallel dimorphic behavior. Together, our results provide the first cellular-resolution, brain-wide account of social sound processing in a vertebrate, from early categorical segregation to thalamic gating and sex-specific population responses in social circuits.

Maternal inheritance of mitochondrial DNA (mtDNA) is a near-universal feature of eukaryotes1, yet the mechanisms that ensure this by preventing paternal mtDNA inheritance have remained unclear. In both Drosophila and humans, mtDNA is actively eliminated from sperm during spermatogenesis, producing mature sperm whose mitochondria lack their genomes2-5. Here we identify Hotaru, a previously uncharacterized, testis-specific GIY-YIG endonuclease, as a central player in this process. We find that Hotaru is expressed in elongated spermatids, localizes to the mitochondrial matrix, and is required for paternal mtDNA elimination. In hotaru mutants, sperm retain mtDNA at levels comparable to those present before the elimination process. Genetic and biochemical analyses show that Hotaru selectively recognizes and cleaves cruciform DNA structures within the mtDNA control region. Together, these findings identify a dedicated nuclease that enforces mitochondrial genome elimination in the animal male germline and reveal that an unexpected structural feature of mtDNA serves as the molecular determinant of its destruction. By recognizing DNA structure rather than specific sequence motifs, this mechanism is inherently robust to the high mutation rate of mitochondrial genomes.

Interoception, the sensing of internal bodily signals, is essential for brain-body interactions and shapes emotion, cognition, and behavior1-5. Subconscious internal signals, including heartbeats or stomach fullness, can rise to conscious awareness, and this process can improve with practice, as seen in meditation, mindful eating, or toilet training in early infancy. Conversely, disrupted interoception is emerging as a common deficit in diverse psychiatric disorders1,3,6,7. Nevertheless, we still lack a fundamental understanding of the neurobiological basis of perception and conscious reporting of internal sensations. Here, we combine genetic and ultra-sensitive optogenetic tools in mice to establish a quantitative framework for studying internal perception. We developed a behavioral task in which mice report detecting non-invasive optogenetic activation of gut mechanosensory neurons, establishing "interoceptive psychophysics". We combine this approach with cellular-resolution imaging and manipulations to reveal the neuronal basis for perception of these internal gut sensations in the interoceptive insular cortex. While representations of sensory stimuli were consistently observed in insular cortex across different tasks, we found that perceptual reports were only encoded during a more difficult psychophysics task, but not during basic detection. Accordingly, manipulation of insular cortex activity affected behavioral reports only in the psychophysics task. These findings reveal a neural basis for perception of internal gut sensations and provide a blueprint for future quantitative exploration of other interoceptive modalities.

Across brain regions and behaviors, neural population activity unfolds as temporally structured sequences that underlie perception, memory, and precisely timed actions1-10. However, how neural circuits transform continuous information streams into transient patterns of activity over time remains poorly understood. A long-standing hypothesis for cerebellar learning posits that the granule cell (GC) layer segments sensory and motor information arriving via mossy fibers (MFs) into temporal basis sets that enable precisely timed motor and cognitive commands11-15. Measurements of such basis sets have been elusive. Using high-speed multiphoton calcium imaging of MF and GC responses to whisker air puff stimulation, we show that prolonged MF activity is transformed into temporally sharpened GC responses that form a sparse population sequence tiling the sensory event in time. Temporal sparsity of GC sequences varied between cerebellar regions. By combining in vivo glutamate imaging with ex vivo synaptic recordings, we identify heterogeneous MF-GC synaptic strength and short-term plasticity as the mechanisms underlying region-specific temporal sparsification. Mathematical modeling predicted that region-specific MF-GC synaptic dynamics generate temporally sparse GC sequences with distinct statistics specifically suited for learning across different timescales. Thus, heterogeneous synaptic dynamics provide a biological substrate for shaping population activity in time, setting the temporal precision of sensorimotor associations underlying adaptive behavior. One-sentence summaryDiverse short-term synaptic dynamics transform input activity patterns into temporally sparse neural sequences in the cerebellar cortex, providing a mechanistic basis for precise temporal learning.

Gene expression is regulated by transcription factors (TFs), which recognize specific DNA sequence motifs. Several hundred putative human TFs, identified mainly by an apparent DNA-binding domain, lack known binding motifs1, and even for well-characterized TFs, it remains controversial to what degree motifs accurately reflect binding sites in living cells2,3. Here, we describe a systematic effort ("Codebook") to determine the sequence specificity of 332 putative and poorly characterized human TFs. Over 4,000 independent experiments, encompassing multiple in vitro and in vivo assays, produced motifs for just over half (177, or 53%), of which most are unique to a single protein, thereby extending the vocabulary of sequence recognition encoded by human TFs by [~]100 distinct motifs. Moreover, binding motifs identified in vitro are strongly enriched within cellular binding sites. Collectively, the data reveal tens of thousands of previously unknown, conserved, and direct TF binding sites across the human genome. These sites are concentrated in promoter regions, and are predictive of gene expression, illustrating that this new data atlas provides an important step forward in decoding the human genome.

Fossilized traces of neuropils, nerves and ganglia have demonstrated that cerebral organization in Cambrian arthropods conforms to a ground pattern defining one of todays two existing euarthropod clades, Mandibulata and Chelicerata1-8. Artiopoda - a third clade including trilobites and soft-bodied relatives - persisted until the late Carboniferous9,10, but its cerebral organization has remained unknown. Here we identify and reconstruct fossilized neural traces of the artiopodan Xandarella spectaculum10, which reveal an expanded prosocerebrum associated with paired ocelli, a truncated protocerebrum supplied by substantial lateral eyes, and salient deutocerebral antennular lobes. This arrangement predicts reliance on chemosensory-guided foraging, with visual processing largely limited to dorsal orientational cues and simple local motion signals. The artiopodan brain thus reveals clade-specific modifications of homologous domains of the euarthropod cerebral ground pattern4,6-8 established in the early Cambrian.

Widespread cell plasticity recognized in fetal intestinal epithelium is preserved in limited fashion in Wnt-responsive adult stem cells and contributes to tumor initiation, progression, and relapse.1, 2, 3 It is unclear which epigenetic features maintain stem-cell properties, restrict adult expression of fetal genes4, and are attenuated in tumors, allowing non-stem cells to replenish targeted tumor stem cells5. Here we show that reversible stemness in normal adult intestinal crypt cells hinges on a dynamic balance between activating H3K27ac and repressive H3K27me3 marks. Cells that leave the Wnt-rich stem-cell niche normally acquire H3K27me3 at thousands of stemness-associated enhancers. Constitutive tumorigenic Wnt activity transforms Apc-/- intestinal stem cells by gradual erosion of H3K27me3 at select enhancers and extends stem-like properties beyond usual anatomic confines; continued depletion of H3K27me3 reactivates enhancers that control growth and expression of a wider swath of fetal genes than appreciated previously. Subsequent focal DNA demethylation at expanded superenhancer domains is associated with tumor growth. Human colorectal cancers also carry evidence of this epigenetic rewiring. Accelerated H3K27me3 loss in mice hastens, and its preservation delays, activation of stemness-related enhancers, superenhancers, and tumor progression. During transformation, H3K27me3 loss at enhancers erases a crucial distinction between stem and non-stem populations, endowing the latter with stemness and providing an explanation for tumor resistance to cancer stem cell targeting. Thus, H3K27me3 at Wnt-responsive enhancers is an intrinsic barrier to intestinal tumorigenesis and aberrant reactivation of hundreds of fetal genes.

Organisms must regulate metabolic resources such as oxygen (O2) and nutrients despite environmental variability and the energetic costs of their own actions1-3. Such regulation can occur reactively, through homeostatic corrections of recent imbalances, or predictively, through allostatic adjustments that anticipate future demand4,5. Predictive regulation is particularly important because metabolic resources often continue to be consumed for seconds to minutes after motor actions cease as tissues repay incurred costs, making it advantageous to prevent depletion before it occurs6. However, the cellular and circuit mechanisms for allostatic control remain largely unknown5,7,8. Using whole-brain neuronal and astroglial imaging and O2 measurements in behaving zebrafish, we identified a noradrenergic-astroglial circuit that detects, anticipates, and prevents internal O2 depletion. We found that swimming exacerbated internal hypoxia with a multi-second delay, but behavioral adaptations occurred before such self-generated hypoxia manifested, suggesting predictive control, confirmed using computational modeling. Noradrenergic neurons in the nucleus of the solitary tract directly detected brain hypoxia and received efference copies of swimming actions; these inputs summed at the level of membrane voltage to increase spiking and norepinephrine release when actions and resource scarcity co-occurred. Astroglia integrated noradrenergic input into prolonged Ca2+ elevation that tracked the O2 cost of recent actions and thereby predicted O2 debt relative to O2 availability, rising [~]8 s before O2 fell. This astroglial prediction reorganized brain-wide activity to suppress locomotion and promote respiration, preempting O2 depletion. Silencing noradrenergic neurons or astroglial signaling abolished these hypoxia coping behaviors, whereas selective activation evoked them. This neuronal-astroglial mechanism constitutes a predictive control system that integrates physiological state with behavioral intent to avert metabolic crisis, revealing a cellular substrate for proactive energy management.

The neural mechanisms underlying flexible perceptual decisions, where the mapping between sensory input and motor action changes depending on context, remain unclear. Here we show that prefrontal and premotor cortex use distinct neural dynamics to implement different computations during flexible decisions. We trained monkeys to discriminate the dominant color of a red-green checkerboard and report their decision by choosing one of two targets1;2. By randomizing the target configuration on a trial-by-trial basis, we ensured a flexible mapping between color (red vs. green) and action choice (left vs. right), necessitating a nonlinear exclusive- or (XOR) computation3-5. We found that neural dynamics in dorsolateral prefrontal cortex (DLPFC) led to higher-dimensional population representations than those in dorsal premotor cortex (PMd). Neural activity in DLPFC first separated by target configuration, then by color choice and action choice after stimulus onset, reflecting the XOR computation. In contrast, neural dynamics in PMd led to lower-dimensional representations that only reflected action choice, the output of the XOR computation. These higher-dimensional representations in DLPFC enabled earlier decoding of both color choice and action choice compared to PMd, and were strongest in anterior and ventral DLPFC6. These findings reveal distinct computations by neural dynamics: prefrontal cortex implements flexible sensorimotor mappings through high-dimensional representations while dorsal premotor cortex reflects only the selected action.

How can humans remember and imagine without vision? Mental time travel, the ability to re-experience past events and envision future ones, is widely assumed to rely on visual imagery and the construction of mental scenes. Blindness provides a critical test of this assumption. Across behavioral interviews, language analyses, and multimodal neuroimaging in congenitally blind, late-blind, and sighted individuals, we show that blind individuals, even those blind from birth, mentally time travel as vividly as sighted people, but construct their inner worlds differently. Sighted participants relied on perceptual detail and activated classic scene-processing regions, whereas blind participants emphasized thoughts and emotions and recruited reorganized occipital cortex. Connectivity analyses revealed strengthened coupling between occipital and medial temporal regions, indicating adaptive reconfiguration of the episodic system. The brain does not require images to imagine: it flexibly builds internal experiences using the representational resources available. Summary ParagraphHow humans reconstruct events that are no longer available to the senses is a fundamental but unresolved question. Remembering the past and imagining the future, known as mental time travel, is a defining feature of human cognition, shaping identity and guiding decisions{superscript 1},{superscript 2}. Prevailing theories assume that such constructions depend on visual imagery, with the minds eye reconstructing events on a visuospatial stage3,. Blindness provides a critical test of this assumption. Across extensive behavioral interviews and multimodal neuroimaging, we find that mental time travel remains phenomenologically intact in blindness, but its scaffolding changes fundamentally. Sighted individuals rely on perceptual detail and activate regions specialized for visual scenes, whereas blind individuals, whether blind from birth or later in life, emphasize thoughts and emotions and reorganize occipital cortex for conceptual strategies,. These contrasting strategies map onto distinct neural signatures, revealing a dissociation between perceptual and conceptual routes to episodic simulation. Together, these findings reveal that the brains capacity to construct internal experience rests on conceptual scaffolding, not perceptual re-creation.

Placebo analgesia has traditionally been explained by top-down cortical regulation of brainstem and spinal pathways. Recent circuit-level work in animal models identified a rostral anterior cingulate-pontine-cerebellar pathway that contributes to expectation-based analgesia, implicating cerebellum circuits in placebo effects1. Building on these findings, we examined pontine and cerebellar contributions within a large individual-participant meta-analysis of human neuroimaging studies of placebo analgesia2 (n = 603). We found that the effects of human pain and placebo converge in cerebellar territories embedded in higher-order cognitive3,4 and action-mode networks5. These regions exhibit placebo-induced anticipatory increases and reduced responses during painful stimulation, which correlate with the magnitude of placebo analgesia, consistent with predictive configuration of the system. Pontine responses also correlate with individual differences in placebo analgesia. In independent Human Connectome Project data (n = 820), pontine activity is functionally connected with cingulate and cerebellar regions implicated in placebo analgesia. Together, these findings support a model in which expectation effects are implemented via predictive configuration of a cortico-pontine-cerebellar system.

Chromosomal instability (CIN) arising from mitotic errors generates pervasive structural and numerical chromosome alterations fueling cancer evolution1-3. Entrapment of missegregated chromosomes within micronuclei exacerbates CIN by fostering repeated rounds of aberrant mitotic segregation4-6 and, following micronucleus rupture, promoting catastrophic chromosomal rearrangement processes such as chromothripsis5-9. Whether cellular mechanisms exist to restrain micronucleus-driven CIN has remained unclear. Developing a live-cell chromatin acidification sensor, we tracked micronuclei from genesis through subsequent cell cycles and observed frequent whole-micronucleus capture and acidification via the autophagy pathway. Autophagic targeting is selective for micronuclei with nuclear envelope defects seeded at mitotic exit. Our data indicate that these defects drive progressive loss of chromatin-nuclear envelope tethering, producing a mechanically altered state that is recognised by the autophagic machinery. Autophagy and rupture represent distinct micronuclear fates with opposing genomic consequences. Single-cell sequencing of fate-matched cells demonstrates complete digestion of the chromosomal contents of autophagy-targeted micronuclei, a process we term chromophagy (chromosome-autophagy). By eliminating micronuclei, chromophagy promotes chromosomal loss and arrests the intergenerational transmission of missegregated chromosomal material. This constrains the mutational consequences of micronucleation and suppresses micronucleus-mediated CIN.

Humans effortlessly learn attributes of other individuals and their complex web of connections through navigating the social world1,2. Yet, the neural mechanisms that transform these transient interactions into structured, multidimensional knowledge remain unknown3,4. Here, using a naturalistic fMRI paradigm5, we develop a computational framework to demonstrate how the human brain factorizes and integrates dynamic social interactions to construct multiplex social graphs. This approach not only predicts neural responses during movie-viewing but also allows for the reconstruction of subjective social cognitive maps directly from brain activity. Crucially, the relational geometry of these reconstructed maps accurately predicts inferred personality traits, indicating that relational and trait knowledge emerge from a shared neural representation reflecting interactional dynamics. These findings reveal an organizing computational principle by which the brain transforms dynamic social experiences into structured cognitive maps6, providing a key mechanism for the emergence of multiplex social knowledge in the human mind.