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Laplane et al. recently provided a valuable framework for understanding cancer evolution through multilevel selection (MLS), distinguishing between MLS1, where groups differ in persistence based on the traits of their constituent cells but do not reproduce or evolve group-level adaptations, and MLS2, where groups themselves reproduce and possess emergent fitness distinct from that of individual cells. However, as the authors themselves acknowledge, applying MLS2 to metastasis is challenging for several reasons. We argue that, rather than behaving as isolated evolutionary units, tumor sites function as components of a distributed system. This perspective suggests that metastasis may be better understood through the lens of selection for function, a framework that explains how traits contributing to system-level persistence can be maintained without requiring group-level reproduction. This approach complements MLS theory and helps account for the resilience of the metastatic system as a whole, namely, the persistence and coordination of multiple tumor sites functioning as a collective rather than as isolated tumors, beyond classical Darwinian models. It also aligns with the view that metastasis may reflect the reactivation of ancient cellular programs in a novel, nonreproductive context.

To an external observer, the goal of cell division is evident from the very shape of the duplicated chromosomes. Cells, however, cannot see-they must proceed by groping in the dark, searching for their own DNA-and a series of sophisticated spatial mechanisms enables them to align and segregate their genetic material. Spatial organization is only part of the challenge: cell division is also a race against time-spending too little or too much time in mitosis can be equally detrimental to cell survival. Dividing cells must not only coordinate the movement of often dozens of chromosomes but must do so with precise timing. Yet, chromosome segregation occurs with remarkable accuracy. In this review, we highlight the role of mitotic chromosomes as a platform to integrate spatial and temporal cues to ensure their successful segregation.

Flow cytometry is a versatile analytical technology for measuring physical and molecular characteristics of individual cells or particles in suspension. The technology has had its greatest impact in immunology, enabling the identification and quantification of rare cell populations within complex mixtures, but applications span diverse biological systems including hematopoietic cells, microorganisms, cultured cells, plant cells, gametes, and disaggregated tissues. Target molecules are typically identified using fluorophore-conjugated antibodies, though alternative labeling strategies exist. A key advantage of flow cytometry is the ability to physically isolate cells of interest for downstream applications such as culture, genomic analysis, or functional studies. The field has undergone substantial evolution from conventional filter-based polychromatic systems to spectral cytometry platforms that capture full emission spectra, enabling higher-parameter analyses and more flexible panel design. This review examines current capabilities and limitations of flow cytometry technology, with emphasis on recent advances in spectral detection, quantitative standardization, and computational analysis. We discuss remaining technical challenges and explore emerging opportunities for innovation in excitation systems, detector technology, and integration with artificial intelligence-based analysis platforms. Addressing these challenges will be essential for cytometry to continue driving biological discovery and clinical applications in the coming decades.

How cells repair oxidative damage to DNA has been studied for over 60 years. Recent evidence confirms that the base excision repair (BER) machinery not only acts to restore an intact double DNA helix by replacing oxidized bases, but under some circumstances, BER goes awry, generating double-strand breaks and provoking chromosome fragmentation. This fragmentation can lead to extensive genomic rearrangements that correlate with oncogenesis. Whether the BER factors suppress or promote DNA damage depends on multiple parameters: the nature of the damage, the clustering of modified bases, the pathway of BER chosen, and chromatin remodelers. Recent data leading to this unexpected role for BER are reviewed here.

Human immunodeficiency virus type 1 (HIV-1) possesses an envelope enriched with a specific set of host plasma membrane (PM) lipids, a composition that is critical for viral infectivity. Virus budding is initiated by the binding of the viral Gag protein to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂) located in the inner leaflet of the PM. However, the mechanism by which inner leaflet-associated Gag protein contributes to the enrichment of specific outer leaflet lipids, such as sphingomyelin (SM) and cholesterol (Chol), remains poorly understood. Visualization of endogenous lipids using specific lipid probes and advanced microscopy has revealed that Gag multimerization reorganizes SM- and Chol-rich lipid domains in a curvature-dependent manner. To further elucidate the molecular mechanisms underlying Gag-induced selective lipid enrichment across the bilayer, two potential scenarios are discussed: one involving interdigitation and the other involving Chol enrichment through flip-flop. These models are considered in the context of existing literature describing the distribution and interactions of SM, PI(4,5)P₂, and Chol within the PM.

The protein kinase C (PKC) family comprises enzyme kinases that regulate cell survival, metabolism, and proliferation. PKC isotypes (PKCs) phosphorylate specific downstream substrates, thereby controlling critical steps in both mitotic and meiotic cell division. Throughout the cell cycle, PKCs orchestrate essential processes, such as chromosome segregation, recombination, and cell cycle progression. In vertebrates, PKCs play essential roles in oogenesis and the early stages of embryo development. Disruption of PKC signaling in mammalian oocytes can lead to errors in chromosome segregation and induce meiotic arrest. Therefore, investigating PKC function in meiosis is crucial for advancing fundamental biological research and for developing new approaches to infertility treatment.

Cutaneous wound repair is tightly regulated by numerous signaling pathways that coordinate a multiphased response. The repair process includes a proliferative phase that forms granulation tissue at the wound base and re-epithelialization of the wound surface. Two of the signaling pathways that regulate the proliferative phase are Wnt/β-catenin and Notch, stimulating the proliferation of keratinocytes and fibroblasts, respectively. While ephrin-Eph signaling pathways also induce keratinocyte proliferation, their contribution to cutaneous wound repair is less defined. In distal limb wounds on horses, the proliferative phase is often characterized by the formation of excessive granulation tissue that delays healing by impeding keratinocyte migration from the wound margin. Comparison of normal and aberrant healing makes distal limb horse wounds well-suited for defining molecular mechanisms that regulate repair during the proliferative phase and identifying targets that promote healthy wound healing. We hypothesize that ephrin-Eph signaling pathways that stimulate keratinocyte proliferation provide an unexplored but effective target for accelerating re-epithelialization in distal limb wounds of the horse. As re-epithelialization is a key to physiologic healing in many mammals, we further hypothesize that ephrin-Eph signaling pathways offer targets for enhanced wound repair in humans.

IL-12 is a proinflammatory cytokine secreted by antigen-presenting cells. It promotes the differentiation of cytotoxic T cells, which makes it a strong candidate to boost the antitumor immune response in cancer patients. While its first use in humans faced severe toxicity, more recent approaches have been taken to limit toxicity while retaining its biologic function. These strategies, summarized in this review, include systemic and local delivery of IL-12 and demonstrated promising results in murine tumor models. However, their translation in cancer patients was met with limited efficacy. Recent evidence indicates that exposure to IL-12 results in the expression of immunoregulatory molecules by T cells, suggesting the existence of a negative feedback loop that might impair the antitumor immune response. Therefore, a more thorough understanding of the biology of IL-12 in the context of cancer is crucial to advance the design of novel clinical trials. This approach can lead to improved therapy regimens and promising results in the future.