Communications Biology最新文献

The Spindle Assembly Checkpoint (SAC) is vital for proper chromosome segregation during cell division and for maintaining genomic integrity; its disruption can cause aneuploidy and tumors. The BUB gene family ensures SAC fidelity by regulating kinetochore-microtubule attachments and mitotic progression. Dysregulation leads to chromosomal instability (CIN), contributing to cancer progression, heterogeneity, metastasis, and therapy resistance. Beyond mitosis, BUB proteins influence DNA repair, chromatin remodeling, transcription, and immune responses. They interact with cell cycle and genome stability pathways, impacting cancer prognosis and therapy response. Research is ongoing to validate BUB proteins as biomarkers and develop inhibitors, possibly combined with immunotherapies or DNA-damaging agents for resistant tumors. This review  summarizes their functions, highlighting their potential in personalized cancer treatment.

Number sense, the ability to estimate and compare numerical quantities, emerges early in development and is widespread across species. Despite decades of work on behavioural and neural correlates of numerosity, the genetic and mechanistic foundations remain poorly integrated. We propose a review and perspective that brings together evidence from vertebrates. Our unique focus relies on how genetic variation, brain lateralisation, and neural circuit organisation across development shape number cognition. We highlight zebrafish (Danio rerio) and chicks (Gallus gallus) as complementary comparative models that can uncover conserved principles and novel mechanisms, opening new avenues for studying the biological bases of numerical cognition and its disorders from the very early developmental stages.

The cytokine interleukin-6 orchestrates inflammation through two distinct pathways of receptor activation: anti-inflammatory classic signalling via membrane-bound interleukin-6 receptor and pro-inflammatory trans-signalling via soluble interleukin-6 receptor. Current interleukin-6-targeted therapies block both pathways, thereby disrupting essential homeostatic functions initiated by classic signalling. We here show a high-affinity, human-specific antibody that selectively inhibits interleukin-6 trans-signalling. This antibody maintains classic signalling-induced expression of hepatic acute phase genes while completely blocking trans-signalling-induced activation of endothelial cells. By targeting the domain D2 of membrane-bound and soluble human interleukin-6 receptor, the antibody selectively prevents formation of the trans-signalling receptor complex without interfering with ligand binding. This selective blockade demonstrates that human interleukin-6 classic and trans-signalling proceed through distinct receptor assemblies. Our findings describe mechanistic insight into interleukin-6 receptor assembly and provide a strategy to suppress inflammatory interleukin-6 activity while preserving regenerative and anti-inflammatory signalling, thus offering both conceptual and potential therapeutic advances in the targeted modulation of cytokine signalling networks.

KCNQ1 encodes a voltage-gated potassium channel implicated in peripheral and neurological disorders, but its role in human neurodevelopment remains unclear. We generated KCNQ1 knockout (KO) human induced pluripotent stem cells and differentiated them into neural stem cells (NSCs) and cortical neurons. KCNQ1-deficient NSCs show impaired neurite outgrowth, linked to reduced cell adhesion and disrupted neural cell adhesion molecule signalling, a phenotype reproduced by pharmacological KCNQ1 inhibition. Multi-omics and follow-up analyses reveal mitochondrial dysfunction, including reduced mitochondrial copy number and ATP synthase expression. KO cells also show impaired insulin signalling, with diminished insulin receptor gene expression and altered RAS-MAPK and PI3K-AKT pathways. In differentiated neuronal cultures, KCNQ1 loss decreases synaptic activity and maintains an immature transcriptional profile. Together, these findings identify a role for KCNQ1 in regulating cell adhesion, mitochondrial function, insulin signalling, and neuronal maturation, expanding our understanding of processes that may contribute to neurological manifestations associated with KCNQ1-related disorders.

Deriving sequential information from complex sounds is a challenge for auditory systems, yet it remains unclear whether humans and nonhuman species integrate multidimensional cues or prioritize a single dimension when processing multidimensional input. We investigated how humans and zebra finches (Taeniopygia guttata) process concurrent acoustic cues using an identical behavioural paradigm with complex-tone sequences. By presenting probe stimuli that selectively preserved or disrupted either pitch or formant trajectory, we quantified these processing strategies. We show that zebra finches employ an additive integration strategy, treating pitch and formant trajectories as complementary components of a unified auditory pattern. In contrast, humans exhibit a dominant reliance on pitch. Experience further modulates this bias, with trained human listeners recruiting secondary cues to preserve learned relational structure when pitch is unreliable. These findings imply a cross-species divergence in auditory representation, suggesting that auditory processing is shaped by an interplay of species-specific priorities and experience-dependent functional substitution.

Parvalbuminergic (PV) interneurons are central to cortical network stability and psychiatric vulnerability. Here, we identify DNA methyltransferase 1 (DNMT1) as a key epigenetic regulator linking PV interneuron function to glial and extracellular matrix remodeling. Conditional PV-specific Dnmt1 deletion, combined with single-nucleus RNA-seq (snRNA-seq), snATAC-seq, in vivo electrophysiology, histology, and behavioral analyses, revealed that DNMT1 loss increases PV spiking but reduces inhibitory efficacy, driving network desynchronization and depression- and anxiety-like behavior in mice. These physiological changes were accompanied by non-cell-autonomous transcriptional and chromatin alterations, affecting perineuronal net (PNN) organization and neuron-glia communication. Cell-cell communication analyses predicted reorganized perisomatic signaling, and compartmental modeling of oligodendrocyte lineage dynamics further revealed impaired formation of PNN-supporting perineuronal oligodendrocytes, consistent with a tissue-level reduction in PNN integrity. Together, our findings demonstrate that DNMT1 maintains inhibitory circuit stability through PV interneuron function, secondarily shaping glial states and extracellular scaffolds to support cortical network synchronization and affective behavior.

Regional diversification patterns are increasingly being used to investigate spatial heterogeneity in biodiversity evolution and its drivers. However, estimating and interpreting regional diversification rates is complicated by the fact that regional diversity fluctuations reflect multiple biological processes and may be more sensitive to temporal sampling bias than global patterns. Here, we assess the biological fidelity and sampling sensitivity of regional diversification rates using fossil occurrences of marine invertebrates. We show that immigrations and extirpations account for up to 76% of apparent plate-level generic turnover. Moreover, regional diversity fluctuations are more strongly shaped by preservation, sampling, and tectono-sedimentary history than global patterns. In widely distributed groups, global analyses integrate data across regions and environments, dampen region-specific biases, and recover a higher proportion of shared biological signal. Global analyses therefore remain indispensable for inferring macroevolutionary dynamics over deep time.

Worldwide reef ecosystem degradation is inspiring efforts to enhance in-situ coral larvae settlement onto degraded or artificial reefs. Here we simultaneously test three approaches for enhancing settlement over two weeks in Kāne'ohe Bay, O'ahu, Hawai'i. Nineteen artificial structures, mimicking natural reef mesoscale roughness, were deployed along two transect lines at distances between 1 and 42 m from an "acoustic enrichment" underwater speaker broadcasting healthy reef sound. Twelve additional cinder blocks supporting micro-habitat structures designed to attenuate flow were also deployed at various distances. Some micro-habitats were coated with a living bacteria reef ink (Brink) to further induce larval settlement. Statistical regressions identify Brink presence, structure type, and speaker distance to 20 m as significant factors in predicting coral larval settlement density, but conclusions about acoustic enrichment efficacy are tentative. The cumulative effects of acoustic enrichment, living microbial materials, and custom-designed habitats on enhancing in-situ larval settlement justify further scaled-up reef restoration trials.

Pseudomonas aeruginosa is a highly drug-resistant pathogen that poses a major challenge to clinical treatment. Bacteriophages encode diverse regulatory proteins that can alter host cellular processes during infection. Here we show that the ΦPA1019-encoded transcription factor Gp53 regulates bacterial physiology by targeting key host pathways. Gp53 expression reduces bacterial growth, motility, and biofilm formation, and causes filamentous cell morphology. Transcriptomic analysis reveals that Gp53 alters the expression of 3,342 genes, including genes involved in cell division and virulence-associated processes. DNA-binding assays demonstrate that Gp53 directly represses promoters of key host genes, including ftsZ, fleQ, pslA, and amrZ. Gp53-mediated repression of ftsZ disrupts Z-ring formation and inhibits cell division, while ftsZ expression restores these defects. Structural and mutational analyses identify residues important for Gp53-DNA interaction. Together, these findings reveal a phage-encoded mechanism that coordinately interferes with bacterial cell division and virulence-associated pathways, providing mechanistic insights into host transcriptional regulation during phage infection and expanding our understanding of phage-host interactions.

Salinity has been identified as a primary factor structuring community composition in global diversity assessments of free-living bacteria in non-extreme environments. It remains unknown whether the same is true for protists. Moreover, changes in alpha diversity of both bacteria and protists across the brackish salinity gradient remain elusive. Here, we analyzed protist and bacterial diversity using DNA metabarcoding across 398 surface water samples synchronized with national monitoring of the Baltic Sea and the Kattegat-Skagerrak. We show that salinity, unlike other environmental factors, had a stronger effect on bacterial than on protist community composition. Likewise, protist taxonomic units tended to have broader salinity niches than bacterial ones. In contrast, protist but not bacterial alpha diversity (richness) increased with salinity. Bacterial alpha diversity was similar across salinities despite drastic changes in community composition, as marine-associated taxa steadily replaced freshwater-associated ones. Conversely, marine-associated protists dominated across most of the salinity gradient, with fewer taxonomic units adapted to lower salinities. Overall, the diversity of protists but not bacteria followed patterns consistent with local adaptation as observed in other groups of organisms. Ultimately, the observed patterns form a baseline for environmental monitoring and suggest unexplored differences between bacterial and protist eco-evolutionary dynamics.