bims-cediti 2025-04-20 papers

bims-cediti

Biomed News

on Cell death in innate immunity, inflammation, and tissue repair

Issue of 2025–04–20
fourteen papers selected by
Kateryna Shkarina, Universität Bonn

Innate immune sensor NLRP3 drives PANoptosome formation and PANoptosis.
Unraveling the mechanisms of NINJ1-mediated plasma membrane rupture in lytic cell death and related diseases.
Hypothermia protects against ventilator-induced lung injury by limiting IL-1β release and NETs formation.
Gasdermin D deficiency aggravates nephrocalcinosis-related chronic kidney disease with rendering macrophages vulnerable to necroptosis.
The role of heme in sepsis induced Kupffer cell PANoptosis and senescence.
Mechanisms and immune crosstalk of neutrophil extracellular traps in response to infection.
The Regulatory Role of NcRNAs in Pyroptosis and Disease Pathogenesis.
RabGAP1L modulates Rab7A and Rab10 to orchestrate cell-autonomous immunity.
Yersinia pestis Actively Inhibits the Production of Extracellular Vesicles by Human Neutrophils.
Serine protease Rv2569c inhibits inflammatory response and promotes intracellular survival of Mycobacterium tuberculosis by targeting the RhoG-NF-κB-NLRP3 pathway.
Mechanical Force Triggers Macrophage Pyroptosis and Sterile Inflammation by Disrupting Cellular Energy Metabolism.
Bacterial biofilm-derived H-NS protein acts as a defense against Neutrophil Extracellular Traps (NETs).
Thermal proteome profiling reveals meltome upon NLRP3 inflammasome activation.
Macrophages maintain signaling fidelity in response to ligand mixtures.

J Immunol. 2025 Apr 18. pii: vkaf042. [Epub ahead of print]

Innate immune sensor NLRP3 drives PANoptosome formation and PANoptosis.

Bhesh Raj Sharma, Sk Mohiuddin Choudhury, Hadia M Abdelaal, Yaqiu Wang, Thirumala-Devi Kanneganti.

  Inflammasomes are multiprotein innate immune complexes formed in response to infections, tissue damage, or cellular stress that promote the maturation and release of IL-1β/IL-18 and are implicated in lytic cell death. The NLRP3 inflammasome is canonically activated by an initial priming event followed by an activation stimulus, leading to rapid cell death that occurs through caspase-1 (CASP1) and gasdermin D (GSDMD) activation, called pyroptosis. CASP1- and GSDMD-deficient cells are protected from the rapid LPS plus ATP-induced pyroptosis. However, innate immune responses physiologically occur over time, extending beyond minutes to hours and days. Therefore, in this study, we assessed lytic cell death beyond the early timepoints. While cells lacking the innate immune sensor NLRP3 were protected from cell death induced by the canonical NLRP3 trigger, LPS priming and ATP stimulation (LPS plus ATP), for extended time, CASP1- and GSDMD-deficient cells started to lyse in a time-dependent manner after 2 h. Nevertheless, robust IL-1β and IL-18 release was still dependent on CASP1 activation. These data suggested that NLRP3 engages an additional innate immune, lytic cell death pathway. Indeed, LPS plus ATP induced the activation of caspases and RIPKs associated with PANoptosis in WT cells, and cells deficient in PANoptosis machinery were protected from cell death for extended times. A PANoptosome complex containing NLRP3, ASC, CASP8, and RIPK3 was observed by microscopy in WT, as well as CASP1- or GSDMD-deficient, cells by 30 min post-stimulation. Overall, these findings highlight the central role of NLRP3 as a PANoptosome sensor. Given the physiological role of innate immune cell death, PANoptosis, in health and disease, our study emphasizes the importance of a comprehensive understanding of PANoptosomes, and their components, as therapeutic targets.

Keywords:  PANoptosome; RIPK; caspase; inflammasome; inflammation

DOI:  https://doi.org/10.1093/jimmun/vkaf042
Int J Biol Macromol. 2025 Apr 15. pii: S0141-8130(25)03717-1. [Epub ahead of print]309(Pt 4): 143165

Unraveling the mechanisms of NINJ1-mediated plasma membrane rupture in lytic cell death and related diseases.

Ji-Yan Yang, Chen-Hua Luo, Kun-Bo Wang, Xin-Yu Tu, Yun-Ying Xiao, Ye-Tong Ou, Yan-Xin Xie, Cha-Xiang Guan, Wen-Jing Zhong.

  Plasma membrane rupture (PMR), the ultimate event during lytic cell death, releases damage-associated molecular patterns (DAMPs) that trigger inflammation and immune responses in the development of various diseases. Recent years have witnessed significant advances in understanding the PMR mediated by ninjurin1 (NINJ1) in different lytic cell death processes. NINJ1 oligomerizes and ruptures the membrane in pyroptosis and other lytic cell death, participating in the pathogenesis of multiple diseases. Although the membrane-permeabilizing function of NINJ1 is well recognized, the role of NINJ1 in different types of lytic cell death and its impact on multiple disease processes have yet to be fully elucidated. This review summarizes the latest advances in the mechanisms of NINJ1-mediated PMR, discusses the membrane-inducing activity of NINJ1 in different lytic cell death, explains the implications of NINJ1 in lytic cell death-related diseases, and lists the inhibitory strategies for NINJ1. We expect to provide new insights into targeting NINJ1 to suppress lytic cell death for therapeutic benefit, which may become a new strategy to control inflammatory cell lysis-related diseases.

Keywords:  DAMPs; Inflammatory disease; Membrane rupture; NINJ1; Regulated cell death

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143165
bioRxiv. 2025 Apr 03. pii: 2024.09.02.610778. [Epub ahead of print]

Hypothermia protects against ventilator-induced lung injury by limiting IL-1β release and NETs formation.

Nobuyuki Nosaka, Vanessa Borges, Daisy Martinon, Timothy R Crother, Moshe Arditi, Kenichi Shimada.

Although mechanical ventilation is a critical intervention for acute respiratory distress syndrome (ARDS), it can trigger an IL-1β-associated complication known as ventilator-induced lung injury. In mice, we found that LPS and high-volume ventilation, LPS-HVV, leads to hypoxemia with neutrophil extracellular traps (NETs) formation in the alveoli. Furthermore, Il1r1 -/- LPS-HVV mice did not develop hypoxemia and had reduced NETs, indicating that IL-1R1 signaling is important for NETs formation and hypoxemia. Therapeutic hypothermia (TH) is known to reduce the release of inflammatory mediators. In LPS-HVV mice, TH (32 °C body temperature) prevented hypoxemia development, reducing albumin leakage, IL-1β, gasdermin D (GSDMD) and NETs formation. We also observed that LPS-primed macrophages, when stimulated at 32°C with ATP or nigericin, release less IL-1β associated with reduced GSDMD cleavage. Thus, hypothermia is an important modulating factor in the NLRP3 inflammasome activation, IL-1β release and NETs formation, preventing LPS-HVV-induced acute respiratory failure.

DOI: https://doi.org/10.1101/2024.09.02.610778
Cell Death Dis. 2025 Apr 13. 16(1): 283

Gasdermin D deficiency aggravates nephrocalcinosis-related chronic kidney disease with rendering macrophages vulnerable to necroptosis.

Yoshihiro Kusunoki, Chenyu Li, Hao Long, Kanako Watanabe-Kusunoki, Meisi Kuang, Julian Aurelio Marschner, Andreas Linkermann, Stefanie Steiger, Hans-Joachim Anders.

Several forms of regulated necrosis contribute to the pathogenesis of crystal nephropathy, however, the role of pyroptosis, an inflammatory form of cell death involving the formation of gasdermin-D pores in internal and external cell membranes, in this condition remains unknown. Our transcriptional and histological analyses suggest that Gsdmd in tubulointerstitital cells may contribute to the pathogenesis of chronic oxalate nephropathy. However, genetic deletion of Gsdmd exacerbated oxalate nephropathy in mice in association with enhanced CaOx crystal deposition and accelerated tubular epithelial cell injury. Pharmacological inhibition of necroptosis reversed this effect. Indeed, Gsdmd-/- bone marrow-derived macrophages were more prone to undergo necroptosis when stimulated with CaOx crystals compared to their wildtype counterparts. We conclude that gasdermin D suppresses the necroptosis pathway, which determines the outcome of oxalate nephropathy-related nephrocalcinosis.

DOI: https://doi.org/10.1038/s41419-025-07620-1
Cell Death Dis. 2025 Apr 13. 16(1): 284

The role of heme in sepsis induced Kupffer cell PANoptosis and senescence.

Tingting Li, Joseph Adams, Peilin Zhu, Tao Zhang, Fei Tu, Amy Gravitte, Xiaojin Zhang, Li Liu, Jared Casteel, Valentin Yakubenko, David L Williams, Chuanfu Li, Xiaohui Wang.

Elevated heme levels, a consequence of hemolysis, are strongly associated with increased susceptibility to bacterial infections and adverse sepsis outcomes, particularly in older populations. However, the underlying mechanisms remain poorly understood. Using a cecal ligation and puncture (CLP) model of sepsis, we demonstrate that elevated heme levels correlate with Kupffer cell loss, increased bacterial burden, and heightened mortality. Mechanistically, we identify mitochondrial damage as a key driver of heme- and bacterial-induced Kupffer cell PANoptosis, a form of cell death integrating pyroptosis, apoptosis, and necroptosis, as well as cellular senescence. Specifically, heme activates phospholipase C gamma (PLC-γ), facilitating the translocation of cleaved gasdermin D (c-GSDMD) to mitochondria, resulting in GSDMD pore formation, mitochondrial dysfunction, and the release of mitochondrial DNA (mtDNA) during bacterial infection. This mitochondrial damage amplifies PANoptosis and triggers the cGAS-STING signaling pathway, further driving immune senescence. Notably, PLC-γ inhibition significantly reduces mitochondrial damage, cell death, and senescence caused by heme and bacterial infection. Furthermore, we show that hemopexin, a heme scavenger, effectively mitigates sepsis-induced Kupffer cell death and senescence, enhances bacterial clearance, and improves survival outcomes in both young and aged mice. These findings establish mitochondrial damage as a central mediator of heme induced Kupffer cell loss and highlight PLC-γ inhibition and hemopexin administration as promising therapeutic strategies for combating sepsis associated immune dysfunction.

DOI: https://doi.org/10.1038/s41419-025-07637-6
mBio. 2025 Apr 16. e0018925

Mechanisms and immune crosstalk of neutrophil extracellular traps in response to infection.

Qi Liu, Ruke Chen, Ziyan Zhang, Zhou Sha, Haibo Wu.

  Neutrophil extrusion of neutrophil extracellular traps (NETs) in a process called NETosis provides immune defense against extracellular bacteria. It has been observed that bacteria are capable of activating neutrophils to release NETs that subsequently kill them or at least prevent their local spread within host tissue. However, existing studies have mainly focused on the isolated function of NETs, with less attention given to their anti-bacterial mechanisms through interactions with other immune cell populations. The net effect of these complex intercellular interactions, which may act additively, synergistically, or antagonistically, is a critical determinant in the outcomes of host-pathogen interactions. This review summarizes the mechanisms underlying classic NET formation and their crosstalk with the immune system, offering novel insights aimed at balancing the anti-microbial function with their potential inflammatory risks.

Keywords:  adaptive immunity; bacterial infection; evasion; innate immunity; neutrophil; neutrophil extracellular traps (NETs)

DOI:  https://doi.org/10.1128/mbio.00189-25
Cell Biochem Biophys. 2025 Apr 18.

The Regulatory Role of NcRNAs in Pyroptosis and Disease Pathogenesis.

Shaocong Wang, Xinzhe Chen, Kun Wang, Sumin Yang.

  Non-coding RNAs (ncRNAs), as critical regulators of gene expression, play a pivotal role in the modulation of pyroptosis and exhibit a close association with a wide range of diseases. Pyroptosis is a form of programmed cell death mediated by inflammasomes, characterized by cell membrane perforation, release of inflammatory cytokines, and a robust immune response. Recent studies have revealed that ncRNAs influence the initiation and execution of pyroptosis by regulating the expression of pyroptosis-related genes or modulating associated signaling pathways. This review systematically summarizes the molecular mechanisms and applications of ncRNAs in diseases such as cancer, infectious diseases, neurological disorders, cardiovascular diseases, and metabolic disorders. It further explores the potential of ncRNAs as diagnostic biomarkers and therapeutic targets, elucidates the intricate interactions among ncRNAs, pyroptosis, and diseases, and provides novel strategies and directions for the precision treatment of related diseases.

Keywords:  Diseases; Mechanism; Pyroptosis; ncRNAs

DOI:  https://doi.org/10.1007/s12013-025-01720-7
Cell Rep. 2025 Apr 16. pii: S2211-1247(25)00370-5. [Epub ahead of print]44(5): 115599

RabGAP1L modulates Rab7A and Rab10 to orchestrate cell-autonomous immunity.

Atsuko Minowa-Nozawa, Takashi Nozawa, Kazunori Murase, Ichiro Nakagawa.

  Cell-autonomous immunity protects cells by utilizing membrane trafficking to detect and counteract diverse microbial pathogens, including selective autophagy and extracellular expulsion. However, the mechanisms underlying the mutual regulation among these systems has remained unknown. Here, we demonstrate that Rab GTPase-activating protein 1-like (RabGAP1L) modulates cell-autonomous immune responses via inactivation of two distinct Rab GTPases during group A Streptococcus (GAS) infection. Confocal microscopy analyses revealed that Rab7A positively regulates selective autophagy induction against GAS by facilitating endolysosomal trafficking and that Rab7A and Rab10 negatively regulate GAS expulsion from infected cells by inhibiting Rab11A-positive recycling endosome formation. RabGAP1L suppressed these pathways via inactivation of Rab7A and Rab10. By contrast, ATG7 and ATG5 knockout, resulting in autophagy deficiency, increased RabGAP1L-dependent bacterial expulsion from infected cells via the endocytic recycling pathway. Our findings suggest a regulatory mechanism of cell-autonomous immunity mediated by RabGAP1L, which contributes to the efficient elimination of intracellular pathogens.

Keywords:  CP: Cell biology; CP: Immunology; Rab10; Rab7A; RabGAP1L; cell-autonomous immunity; extracellular expulsion; group A Streptococcus; selective autophagy

DOI:  https://doi.org/10.1016/j.celrep.2025.115599
J Extracell Vesicles. 2025 Apr;14(4): e70074

Yersinia pestis Actively Inhibits the Production of Extracellular Vesicles by Human Neutrophils.

Katelyn R Sheneman, Timothy D Cummins, Michael L Merchant, Joshua L Hood, Silvia M Uriarte, Matthew B Lawrenz.

  Yersinia pestis is the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signalling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation. Previous work has shown that Y. pestis inhibits phagocytosis and degranulation by neutrophils. Manipulation of these key vesicular trafficking pathways suggests that Y. pestis influences extracellular vesicle (EV) secretion, cargo selection, trafficking and/or maturation. Our goals were to define the EV population produced by neutrophils in response to Y. pestis and determine how these vesicles might influence inflammation. Towards these goals, EVs were isolated from human neutrophils infected with Y. pestis or a mutant lacking bacterial effector proteins known to manipulate host cell signalling. Mass spectrometry data revealed that cargoes packaged in EVs isolated from mutant infected cells were enriched with antimicrobial and cytotoxic proteins, contents which differed from uninfected and Y. pestis infected cells. Further, EVs produced in response to Y. pestis lacked inflammatory properties observed in those isolated from neutrophils responding to the mutant. Together, these data demonstrate that Y. pestis actively inhibits the production of antimicrobial EVs produced by neutrophils, likely contributing to immune evasion.

Keywords:  Yersinia pestis; Yop effectors; human neutrophils (hPMNs); plague; type 3 secretion system (T3SS)

DOI:  https://doi.org/10.1002/jev2.70074
Int J Biol Macromol. 2025 Apr 12. pii: S0141-8130(25)03574-3. [Epub ahead of print]309(Pt 4): 143022

Serine protease Rv2569c inhibits inflammatory response and promotes intracellular survival of Mycobacterium tuberculosis by targeting the RhoG-NF-κB-NLRP3 pathway.

Xinxin Zang, Jiajun Zhang, Tingting Feng, Hui Wang, Yingying Cui, Yanyan Jiang, Chunwen Chen, Siguo Liu, Guanghui Dang.

  Innate immunity is dominant in protecting the host's defense against intracellular bacterial infections. The secretion of IL-1β and activation of NLRP3 inflammasome in macrophages play a critical role in combating Mycobacterium tuberculosis (M.tb) infections. M.tb is an extremely successful intracellular pathogen that evades host innate immunity by interfering with a wide range of macrophage functions. However, the precise infection mechanism remains unclear. This study demonstrates that the mycobacterial serine protease Rv2569c interacts with RhoG in macrophages, effectively blocking the NF-κB signaling pathway's initiation and suppressing NLRP3 inflammasome activation, ultimately leading to a decrease in IL-1β secretion and promoting mycobacterial survival within macrophages. To investigate the role of Rv2569c in M.tb infection, an Rv2569c-deficient strain (H37RvΔRv2569c) was used to demonstrate a weakened suppression of the inflammatory response and lower intracellular survival compared to the wild-type (H37Rv) and complemented strain (H37RvΔRv2569c + Rv2569c) through in vitro and in vivo experiments. The findings provide the first proof that RhoG serves as an endogenous host sensor for pathogens and that Rv2569c-RhoG-mediated inflammatory response plays a crucial role in mycobacterial immune evasion.

Keywords:  Mycobacterium tuberculosis Rv2569c; NF-κB signaling pathway; NLRP3 inflammasome

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143022
Int J Mol Sci. 2025 Apr 02. pii: 3321. [Epub ahead of print]26(7):

Mechanical Force Triggers Macrophage Pyroptosis and Sterile Inflammation by Disrupting Cellular Energy Metabolism.

Hao Tan, Guoyin Yang, Ye Zhu, Xinyi He, Lan Yang, Yun Hu, Leilei Zheng.

  Mechanical force regulates tissue remodeling during orthodontic tooth movement (OTM) by inducing macrophage-mediated sterile inflammatory responses. Pyroptosis, as an inflammatory form of programmed cell death, triggers a robust inflammatory cascade by activating the inflammasome. Although recent reports have demonstrated that pyroptosis can be activated by mechanical force, it remains unclear whether and how orthodontic force induces macrophage pyroptosis and sterile inflammation. In this study, by establishing a rat OTM model and a force-loaded macrophage model, we found that force induces Caspase1-dependent pyroptosis in macrophages and activates sterile inflammation both in vivo and in vitro. Mechanistically, we uncovered that mechanical force disrupts macrophage energy metabolism, characterized by an imbalance between lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase (PDH), as well as mitochondrial dysfunction. Notably, inhibiting pyruvate dehydrogenase kinase 1 (PDK1) effectively restored this metabolic balance, thereby alleviating pyroptosis and sterile inflammation in force-stimulated macrophages. Overall, this study elucidates that force induces macrophage pyroptosis and sterile inflammation, and further identifies imbalances in the LDHA/PDH ratio and mitochondrial dysfunction as pivotal mechanistic features. These insights offer novel perspectives and potential therapeutic targets for the precise and effective modulation of OTM.

Keywords:  energy metabolism; macrophage; mechanical force; orthodontic tooth movement; pyroptosis; sterile inflammation

DOI:  https://doi.org/10.3390/ijms26073321
NPJ Biofilms Microbiomes. 2025 Apr 15. 11(1): 58

Bacterial biofilm-derived H-NS protein acts as a defense against Neutrophil Extracellular Traps (NETs).

A L Hendricks, K R More, A Devaraj, J R Buzzo, F H Robledo-Avila, S Partida-Sanchez, L O Bakaletz, S D Goodman.

Extracellular DNA (eDNA) is crucial for the structural integrity of bacterial biofilms as they undergo transformation from B-DNA to Z-DNA as the biofilm matures. This transition to Z-DNA increases biofilm rigidity and prevents binding by canonical B-DNA-binding proteins, including nucleases. One of the primary defenses against bacterial infections are Neutrophil Extracellular Traps (NETs), wherein neutrophils release their own eDNA to trap and kill bacteria. Here we show that H-NS, a bacterial nucleoid associated protein (NAP) that is also released during biofilm development, is able to incapacitate NETs. Indeed, when exposed to human derived neutrophils, H-NS prevented the formation of NETs and lead to NET eDNA retraction in previously formed NETs. NETs that were exposed to H-NS also lost their ability to kill free-living bacteria which made H-NS an attractive therapeutic candidate for the control of NET-related human diseases. A model of H-NS release from biofilms and NET incapacitation is discussed.

DOI: https://doi.org/10.1038/s41522-025-00691-0
Mol Cell Proteomics. 2025 Apr 16. pii: S1535-9476(25)00070-2. [Epub ahead of print] 100972

Thermal proteome profiling reveals meltome upon NLRP3 inflammasome activation.

Chen Yang, Ling Wang, Yuchen Liu, Yuehui Zhang, Chaozhi Jin, Jiale Cheng, Limin Shang, Longlong Fang, Shanshan Wu, Chuan Chen, Jian Wang.

NLR family pyrin domain containing 3 (NLRP3) involves in inflammasome complex assembly and innate immunity. Activation of the NLRP3 inflammasome induces conformational alterations in protein complexes, influencing their interactions with other molecules, which in turn affects protein thermal stability. To investigate the proteome-wide thermal stability alterations induced by NLRP3 inflammasome activation, we conducted a comprehensive analysis of meltome dynamics using thermal proteome profiling (TPP). Our analysis identified 337 proteins exhibiting alterations in thermal stability upon NLRP3 inflammasome activation. Subsequently, we validated three proteins by the cellular thermal shift assay (CETSA). Notably, our findings reveal that the majority of these proteins tend to cluster into distinct macromolecular complexes. Furthermore, we identify FAM120A as a novel NLRP3 binding partner, with its suppression enhancing caspase-1 activation and IL-1β release in response to NLRP3 agonist. Collectively, these data provide a comprehensive framework for understanding the mechanisms of NLRP3 inflammasome activation and underscore the utility of TPP in exploring proteome-wide thermal stability changes during signaling transduction.

DOI: https://doi.org/10.1016/j.mcpro.2025.100972
bioRxiv. 2025 Apr 01. pii: 2025.03.27.645368. [Epub ahead of print]

Macrophages maintain signaling fidelity in response to ligand mixtures.

Xiaolu Guo, Supriya Sen, Julian Gonzalez, Alexander Hoffmann.

As immune sentinel cells, macrophages are required to respond specifically to diverse immune threats and initiate appropriate immune responses. This stimulus-response specificity (SRS) is in part encoded in the signaling dynamics of the NFκB transcription factor. While experimental stimulus-response studies have typically focused on single defined ligands, in physiological contexts cells are exposed to multi-ligand mixtures. It remains unclear how macrophages combine multi-ligand information and whether they are able to maintain SRS in such complex exposure conditions. Here, we leveraged an established mathematical model that captures the heterogeneous single-cell NFκB responses of macrophage populations to extend experimental studies with systematic simulations of complex mixtures containing up to five ligands. Live-cell microscopy experiments for some conditions validated model predictions but revealed a discrepancy when TLR3 and TLR9 are stimulated. Refining the model suggested that the observed but unexpected ligand antagonism arises from a limited capacity for endosomal transport which is required for responses to CpG and pIC. With the updated model, we systematically analyzed SRS across all combinatorial-ligand conditions and employed three ways of quantifying SRS involving trajectory decomposition into informative trajectory features or machine learning. Our findings show that macrophages most effectively distinguish single-ligand stimuli, and distinguishability declines as more ligands are combined. However, even in complex combinatorial conditions, macrophages still maintain statistically significant distinguishability. These results indicate a robustness of innate immune response specificity: even in the context of complex exposure conditions, the NFκB temporal signaling code of macrophages can still classify immune threats to direct an appropriate response.
Significance ≤120: Macrophages sense diverse pathogens within complex environments and respond appropriately. Experimental studies have found that the NFκB pathway responds with stimulus-specific dynamics when macrophages are exposed to single ligand stimuli. However, it remains unclear complex contexts might erode this stimulus-specificity. Here we systematically studies NFκB responses using a mathematical model that provides simulations of the heterogeneous population of single cell responses. We show that although the model is parameterized to single ligand data it can predict the responses to multi-ligand mixtures. Indeed, model validation uncovered signaling antagonism between two ligands and the underlying mechanism. Importantly, we found that NFκB signaling dynamics distinguish ligands within multi-ligand mixtures indicating a robustness of the NFκB temporal code that was not previously appreciated.

DOI: https://doi.org/10.1101/2025.03.27.645368