The SepN-FraD structural module serves as an anchor and assembly platform for septal junctions in cyanobacteria

Filamentous cyanobacteria rely on septal junctions to coordinate multicellular behavior. Kieninger et al. combine cryo-electron tomography, structure prediction, molecular dynamics simulations, and functional analyses to show that the FraD-SepN structural module forms the core of septal junctions, with SepN constituting the plug and FraD acting as a transmembrane anchor.

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A maternal Polycomb imprint is maintained in early Drosophila development through lower-order methylation states

In rapidly developing embryos, do parental Polycomb states persist long enough to influence chromatin organization in the early embryo? Here, Degen et al. use computational modeling and in vivo experimentation to characterize the maintenance and de novo establishment of Polycomb states in early Drosophila development.

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Myeloid MMP14 couples extracellular proteolysis to inflammatory and metabolic remodeling during obesity

Shao et al. identify macrophage MMP14 as a key regulator linking extracellular matrix proteolysis to inflammatory and metabolic remodeling in obesity. MMP14 promotes endotrophin generation, TLR4-NFκB signaling, and lipid accumulation in macrophages, while myeloid Mmp14 deletion reduces adipose inflammation, fibrosis, hepatic steatosis, and metabolic dysfunction.

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Human adenovirus protein VII inhibits type I IFN production by antagonizing viral RNA sensor RIG-I

During adenovirus infection, host RNA polymerase produces viral-associated RNA that can be recognized by RNA sensor RIG-I. Yu et al. demonstrate that a DNA virus evades RIG-I by using its structural protein, adenoviral preVII protein, to prevent TRIM25 oligomerization, leading to inactivation of RIG-I-mediated IFN signaling.

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Thyroid hormone activation drives fibroblast identity and tumor remodeling in cutaneous squamous cell carcinoma

Di Cicco et al. show that D2-mediated thyroid hormone signaling regulates the activation of cancer-associated fibroblasts in cutaneous squamous cell carcinoma. D2-positive fibroblasts are associated with immunomodulatory and matrix CAF states, metabolic remodeling, collagen deposition, and tumor expansion.

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A telomerase-SUCLG2 signaling axis drives drug resistance by protecting persister cells

Liu et al. reveal that dynamic telomerase regulation parallels pan-cancer drug tolerance. Combining targeted therapies with 6-thio-dG induces chromatin remodeling that downregulates SUCLG2. This severe metabolic disruption effectively prevents drug-tolerant persister cells from evolving into resistant clones.

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Yeast Rpd3L histone deacetylase couples nutrient shifts to genome-wide chromatin reprogramming

Bhattacharya et al. reveal that the histone deacetylase Rpd3 acts as a promoter-poised metabolic gatekeeper that couples carbon source changes to genome-wide chromatin reprogramming in yeast. Based on nutrient availability, Rpd3 complexes redistribute to halt inappropriate transcriptional programs while promoting the correct induction of appropriate genes.

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Distinct metabolic dependency on BCAA defines cancer stemness and malignancy in human triple-negative breast cancer

Triple-negative breast cancer lacks targeted therapies. Matsuura et al. show that claudin-low triple-negative breast cancer cells rely heavily on branched-chain amino acid metabolism to maintain cancer stemness and malignancy. Targeting BCAT1 or reactivating the BCKDH complex disrupts the BCAA-BCKA balance and impairs tumor development, revealing a therapeutic vulnerability.

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Time-resolved proteolipidomics of the human aorta identifies stage-specific lipid-protein modules across development and aging

Cui et al. integrate proteomics and lipidomics to characterize how postnatal ganglioside GM3 accumulation coregulates PMCA-mediated calcium homeostasis, delaying pathological smooth muscle cell phenotypic transitions. Aged aortas exhibit an adult-to-fetal metabolic reversion with impaired amino acid catabolism and reduced GM3, disintegrating these protective adaptations and increasing cardiovascular disease susceptibility.

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A deep-sea rare bacterium exhibits extraordinary metabolic versatility

Li et al. isolate a novel bacterium, named Metabolovarius oceani D14T, from deep-sea water, and reveal its diverse metabolic capabilities and low abundance in nature. D14T is the first cultivated member of a globally distributed bacterial lineage. Its isolation permits experimental insights into rare but metabolically versatile microorganisms.

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Structure of the Beat–Side complex reveals their interaction is required for neuromuscular system wiring

In fruit flies, Beats and Sides are part of the cell surface code necessary for neuronal wiring. Priest et al. report the three-dimensional structure of the Beat-Vc–Side-VI complex. By breaking the Beat-Ia–Side interaction in vivo, authors show that this interaction is required for motor neuron wiring in larvae.

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Bridging neural and immune networks in barrier defense

Gu et al. review how sensory, autonomic, and enteric neural circuits engage in bidirectional communication with immune cells to coordinate host defense, inflammation, and tissue repair across the skin, lung, and gut, positioning neuroimmune crosstalk as a core regulatory network of barrier physiology.

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FOSL1-mediated super-enhancer facilitates pathological scarring

Sun et al. identify FOSL1+ keratinocytes as critical drivers of pathological scar formation. Through super-enhancer-mediated MMP3 transcription, these early-emerging epidermal cells paracrinely induce profound pro-fibrotic and pro-inflammatory phenotypic shifts in dermal fibroblasts, highlighting a crucial epithelial-dermal interaction in pathological scarring.

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Double-ring assembly of mpox virus I3L reveals an unconventional mechanism for ssDNA engagement

Yang et al. describe the cryo-EM structure of the MPXV I3L protein, which forms double-ring complexes with varying subunit stoichiometries via a cyclic tail-insertion mechanism. This architecture sequesters ssDNA within an interior channel, highlighting a specialized strategy for poxvirus genome maintenance and providing potential targets for antiviral development.

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Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation

Striatal medium spiny neurons derived from patients with C9ORF72 repeat expansion mutations show intrinsic hypoexcitability driven by axon initial segment shortening and potassium channel dysregulation. These defects impair spike timing and inhibitory microcircuit precision, identifying striatal dysfunction as a mechanistic contributor to frontotemporal dementia and amyotrophic lateral sclerosis.

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Combining genotoxic gut bacterial strains increases tumor burden and accelerates onset in a germ-free mouse model of colon carcinogenesis

Plitt et al. show that genotoxic bacteria drive colorectal tumorigenesis independent of donor health status. Screening 19 cultured human microbiotas in susceptible mice and >300 strains in vitro, they demonstrate that genotoxicity predicts tumorigenic potential. Combining multiple genotoxic microbes increases tumor burden and shortens time-to-tumor onset.

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Lectins of the Emp47/ERGIC-53 family target misfolded O-mannosylated ER proteins to ER-associated degradation

Lemus et al. identify a pathway for the targeting of misfolded O-mannosylated proteins to ERAD in yeast. They show Emp47/ERGIC-53 family lectins link Pbn1-Gpi14-dependent protein O-mannosylation to Hrd1-mediated degradation, revealing an alternative route for eliminating misfolded proteins that complements classical N-glycan-dependent degradation mechanisms in cells.

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Jagged1+ Tregs mediate lymphatic remodeling in tumor-draining lymph nodes

Xu et al. show that Jag1+ regulatory T cells accumulate in melanoma-draining lymph nodes and support lymphatic remodeling. Treg-specific Jag1 deletion reduces lymph node expansion, lymphatic endothelial cell abundance, and lymphatic drainage without major effects on T cell activation.

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M4-ipRGCs regulate contrast sensitivity in vision

Daly et al. selectively manipulate M4 intrinsically photosensitive retinal ganglion cells (ipRGCs) during in-vivo behavioral assays and map their central projections. Using chemogenetic viruses, M4-ipRGCs do not contribute to circadian photoentrainment or the pupillary light response, but specifically modulate contrast sensitivity threshold, defining a melanopsin-dependent pathway that enhances visual performance.

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Single-nucleotide RNA m6A mapping in bovine preimplantation development reveals site-specific regulation of RPL12 at zygotic genome activation

Iyyappan et al. profile m6A at single-nucleotide resolution during bovine preimplantation development and demonstrate that site-specific m6A on RPL12 is essential for translation and embryonic progression. This study provides a valuable resource for m6A research in bovine embryogenesis and uncovers a critical mechanism by which precise, site-specific m6A regulates embryonic development.

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Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site

Ko et al. demonstrate that two Plasmodium falciparum heat shock protein 90 inhibitors targeting the identical binding site exhibit strikingly divergent resistance profiles. A paradoxical resistance mutation that strengthens rather than weakens drug binding reveals that resistance risk cannot be inferred from binding site identity alone.

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A cold-induced GDF15-secreting adipocyte subpopulation regulates energy homeostasis through endocrine signaling

Wu et al. show that UCP1-deficient brown adipose tissue adapts to cold through emergence of a GDF15-enriched adipocyte subpopulation (U2). These findings reveal a conserved UCP1-GDF15 axis that compensates for impaired thermogenesis to maintain systemic energy balance.

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RelB drives integrin-mediated stress tolerance and relapse in high-grade serous ovarian cancer

Lujano-Olazaba et al. show that ovarian cancer cells expressing integrin αVβ3 have enhanced tumorigenic capacity and are enriched at relapse, suggesting that αVβ3 specifies stress tolerance. Using in vivo models, they demonstrate that genetic knockdown of NF-κB, a stress response pathway, in combination with αVβ3 inhibition reduced relapse and improved survival.

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Physical interactions within the SIR heterochromatin complex potentiate inter-subunit communication and gene repression

Kotz et al. discover a new protein-protein interaction in the SIR gene-silencing complex important for its function. This dynamic interface has the capacity to couple the catalytic activity of the complex to the second stage of the mechanism, chromatin compaction.

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An IGF2BP3-dependent metabolic circuit governs macrophage recruitment and immunosuppression in glioblastoma

Glioblastoma cells shape an immunosuppressive microenvironment by competing for nutrients. Dai et al. show that the m6A reader IGF2BP3 enhances tumor methionine uptake via stabilization of methionine transporter SLC38A2, leading to m6A hypomethylation and CCL5 induction in macrophages. This feedforward circuit promotes macrophage recruitment and sustains intratumoral immunosuppression.

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Structural proteomics reveals that misfolded nascent proteins expose buried lysines for ubiquitination and rapid proteasomal degradation

Jain et al. map ubiquitination sites across the human proteome and show that sites promoting rapid proteasomal degradation occur preferentially at lysines buried within protein cores. These high-flux sites are enriched in newly synthesized, misfolded proteins, revealing how structural defects in nascent proteins are recognized and cleared by the proteasome.

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BCAA metabolism promotes lung cancer tumorigenesis by enhancing cholesterol biosynthesis

Ma et al. show that circulating branched-chain amino acid (BCAA) catabolites are associated with increased lung cancer risk. Leucine is the primary driver, where AUH-mediated leucine catabolism provides carbon sources for cholesterol biosynthesis, synergistically promoting lung tumor initiation and progression via lipid raft-EGFR signaling.

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Comparative population genomics reveals adaptive convergence in two Drosophila species across global environments

Li et al. compare global genomes of D. melanogaster and D. simulans across evolutionary timescales. They show that 12%–17% of adaptively evolving genes are shared between species, with minimal overlap at the nucleotide level, revealing a hierarchical repeatability of adaptation.

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Yap mediates hippo signaling to balance proliferation and differentiation in the developing glandular stomach epithelium

Mu et al. delineate key signaling mechanisms regulating glandular stomach organogenesis during embryonic development. Using a combination of mouse genetic models, 3D organoid systems, and scRNA-seq, they demonstrate that Hippo signaling governs gastric development by balancing epithelial cell proliferation and differentiation through the modulation of cell cycle activity.

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Glioblastoma stem cell growth requires DOT1L-MED23 control of enhancer accessibility

Assaf et al. demonstrate that interplay between DOT1L and the MED23-driven mediator complex controls glioblastoma growth by regulating CCND2 expression. They identify that DOT1L inhibition induces loss of chromatin accessibility at GSC enhancers, a feature that was not evident following loss of MED23.

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