Lamin B receptor (LBR) is an inner nuclear membrane (INM) protein that plays crucial roles in maintaining nuclear architecture and organization of peripheral heterochromatin. Lamins and LBR both contribute to chromatin tethering at the nuclear periphery, and the expression of LBR and A-type lamins is tightly regulated during development to ensure a faithful transition between different chromatin tethering modalities. Despite its well-established association with B-type lamins, the contributions of individual lamin isoforms to LBR localization and anchorage have not been systematically examined. Here, we used mouse embryonic fibroblasts (MEFs) lacking all endogenous lamins (triple lamin knockout: TKO) to assess how specific lamin isoforms and domains regulate LBR subcellular localization and mobility. Whereas ectopic expression of either lamin B1 or lamin B2 was sufficient to tether LBR to the nuclear envelope in TKO cells, expression of lamin A increased the lateral mobility of LBR at the nuclear membrane, resulting in its displacement from the nuclear envelope to the ER. The lamin A-induced displacement of LBR was mediated by phosphorylation of LBR. Overexpression of lamin A in wild-type MEFs similarly increased LBR phosphorylation and promoted its displacement from the nuclear envelope. Collectively, these findings define isoform-specific and antagonistic roles for A-type and B-type lamins in regulating LBR anchorage at the nuclear envelope. In addition, they indicate a lamin A-dependent mechanism that may reflect a broader developmental process, since LBR and lamin A sequentially tether peripheral heterochromatin during development.

Genome replication is temporally regulated during S phase, with specific genomic regions replicating at defined times in a process that is known as replication timing (RT). Based on 3D cytology in replicating nuclei, we previously proposed a model in which maize euchromatin is subdivided into subcompartments distinguished by chromatin condensation and RT. However, whether this compartmentalization reflects a general nuclear architecture that persists throughout the cell cycle was unclear. To test this model, we conducted two orthogonal assays - Hi-C for genome-wide interaction data and 3D FISH for direct visualization of chromatin organization in maize (Zea mays L.). Hi-C analyses revealed distinct patterns of early-S regions exhibited negative insulation scores with long-range contacts, whereas middle-S regions showed the opposite. Early-S regions showed the strongest correlation with epigenomic signatures of open, transcriptionally active chromatin. 3D oligo FISH painting confirmed that early-S and middle-S replicating regions occupy adjacent but largely non-overlapping nucleoplasmic sub-territories throughout interphase stages, including G1. Together, our findings redefine the maize euchromatin "A" compartment as two spatially distinct subcompartments derived from high-frequency RT transitions between early and middle S along the linear genome. These findings have implications for chromatin-templated processes and underscore the importance of RT as a defining feature of genome organization.

Efficient neutrophil chemotaxis requires the integration of mechanical forces and lipid-mediated signaling. While the signaling lipid leukotriene B4 (LTB4) reinforces cellular polarity, how mechanical cues regulate its production remains unclear. We now show that cytosolic phospholipase A2α (cPLA2α), which is essential for the synthesis of LTB4, functions as a nuclear curvosensor. cPLA2α responds to nuclear squeezing by localizing to ceramide-rich inner nuclear membrane microdomains and incorporating onto the exofacial surface of nuclear envelope-derived exosomes. This unique topology enables localized LTB4 synthesis, which synchronizes calcium spikes, promotes myosin light chain II phosphorylation, and sustains polarity and directional persistence after constriction. In neutrophils passing through tight spaces, cPLA2α activity drives the chemotactic response to nuclear squeezing by promoting exosomal LTB4 production and persistence after constriction. These findings uncover a cPLA2α-dependent mechanochemical axis linking nuclear architecture to chemotactic efficiency and offer alternative strategies to modulate inflammatory responses.

The progression from the one-cell to the two-cell stage constitutes a remarkable transition, accompanied by the activation of a specific set of embryonic genes, epigenome reprogramming and nuclear architecture reorganization. Some of these characteristics are recapitulated in vitro with the spontaneous emergence of two-cell-like cells from mouse embryonic stem cells, which exhibit a transcriptomic signature resembling the two-cell stage, including the expression of genes such as Dux, Zscan4 and the repetitive element MERVL, as well as a more relaxed chromatin state. Here we show that interchromosomal and intrachromosomal interactions driven by Zscan4 chromatin factors form during this transition and segregate into a distinct genomic compartment, the Z compartment, independently of cohesin and CCCTC-binding factor. Mechanistically, the formation of Z-DNA, an alternative DNA conformation regulated by polyamine levels, appears to promote the emergence of totipotent-like cells and the establishment of the Z compartment. This compartment is characterized by a decrease in active histone marks and a reduced expression of genes associated with differentiation and late developmental processes. Overall, these findings suggest that Z-DNA formation may have a dual role, first in initiating zygotic genome activation (ZGA) and later in guiding genome compartmentalization to safeguard the totipotent-like state by restricting the expression of non-ZGA genes within a permissive chromatin environment.

Age-related alterations in the immune system-collectively known as immunosenescence-include both quantitative and qualitative changes across various immune cell populations, including B cells, natural killer cells and T lymphocytes, affecting their structure, phenotype and function. While these changes have been characterised biochemically and physiologically, their biophysical manifestations remain less understood, particularly in individuals that achieve exceptional longevity. Here, we investigate the mechanical and structural properties of memory CD4+ T cells from mice across three aging stages: old (72 ± 4 weeks), very old (96 ± 4 weeks) and long-lived (> 120 weeks). We conducted a cross-sectional analysis combining micropipette aspiration, 3D confocal microscopy, spontaneous migration assays and flow cytometry to evaluate cellular stiffness, motility, nuclear morphology and cytoskeletal organisation. Our results confirm previous reports of increased stiffness and reduced migration in T cells from very old mice. However, this trend does not persist in long-lived individuals, who display mechanical and migratory properties similar to younger cohorts. Relative nuclear size (Rn/Rc) and actin organisation also stabilise in this group, suggesting the maintenance of intracellular architecture despite advanced chronological age. Notably, no significant changes were found in the expression levels or distribution of key structural proteins (actin, myosin, vimentin), nor in markers of DNA methylation (5-mC) or cellular senescence (p16). These findings support the concept of mechanical resilience in the immune system as a feature of successful aging, highlighting that certain biophysical traits may be preserved or selectively maintained in extreme longevity. This study provides novel evidence linking T cell mechanics with immune health and longevity and identifies candidate parameters for future investigations into aging biomarkers.

Emerging models of nuclear organization suggest that chromatin forms functionally distinct microenvironments through phase separation. As chromatin architecture is organized at the level of the nucleosome and regulated by histone post-translational modifications, we investigated how these known regulatory mechanisms influence nucleosome phase behavior. By systematically altering charge distribution within the H3 tail, we found that the terminal and central regions modulate the phase boundary and tune nucleosome condensate viscosity differentially, as revealed by microscopy-based assays, microrheology, and simulations. Nuclear magnetic resonance relaxation experiments revealed that H3 tails remain dynamically mobile within condensates, and their mobility correlates with condensate viscosity. These results demonstrate that the number, identity, and spatial arrangement of basic residues in the H3 tail critically regulate nucleosome phase separation. Our findings support a model in which nucleosomes, through their intrinsic properties and modifications, actively shape the local chromatin microenvironment—providing new insight into the histone language in chromatin condensates.

Phenotypic plasticity is a prominent cancer feature that contributes to metastatic potential and resistance to therapy across multiple cancer types. Cancer cell state transitions have been attributed to transcriptional programs, such as the AP1/TEAD-regulated gene network driving the mesenchymal-like (MES) phenotype. In addition, during dissemination, tumor cells are subjected to variable loads of physical mechanical pressure and constriction across transited tissue, which are thought to impact nuclear molecular crowding. How the interplay between mechanical pressure, global 3D nuclear architecture and transcriptional programs contributes to MES identity and metastatic adaptation remains unclear. Using cutaneous melanoma as a model for early dissemination, we integrate in vitro and in vivo epigenomic profiling with nanoscale imaging of cell lines and patient samples to investigate chromatin organization features underlying the MES phenotype. We find that in MES cells, CTCF is relocated from domain boundaries to regulatory regions of EMT-like genes, leading to reduced insulation, extended topological associated domains (TADs) and increased inter-domain contacts, and de novo formation of chromatin hubs. This conformational rewiring, along with loss of heterochromatin, supports nuclear deformability during invasion and dissemination. Conversely, physical constriction of melanocytic cells induces MES-like chromatin features, including CTCF repositioning and heterochromatin loss, and promotes metastasis in vivo. Similarly, pharmacological inhibition of the heterochromatin mark H3K9me3 triggers MES characteristics and increases invasiveness. These results demonstrate that metastatic competency involves both epigenetic and structural nuclear reprogramming, enabling shifts in gene networks and physical adaptability. Our findings reveal mechanistic links between nuclear architecture and aggressive tumor behavior, identifying potential biomarkers and therapeutic targets to intercept metastatic progression.

Periodontal disease is characterized by inflamed gingival tissues and degradation of the gingival extracellular matrix (ECM), yet the role of mechanical cues remains poorly understood. Gingival ECM in periodontal disease showed reduced fibrillar collagen compared to healthy samples. We hypothesized that ECM softening in periodontal disease contributes to inflammation by dysregulating gingival fibroblasts (GFs). A mechanically tunable hydrogel model of the gingival ECM was developed to investigate the mechano-immune crosstalk. Stiff and soft collagen-alginate hydrogels matched the rheological properties of healthy and diseased gingival biopsies respectively. Human donor GFs encapsulated in these stiff hydrogels showed significantly suppressed toll-like receptor-mediated inflammatory responses compared to those in soft hydrogels. The non-canonical NFκB pathway and epigenetic nuclear organization directed stiffness-dependent inflammatory responses of GFs. The direct impact of mechanical cues on immune responses was investigated ex vivo by co-culture of donor-derived human GFs with myeloid cells and in human gingival explants. Myeloid progenitors co-cultured with GFs in stiff hydrogels differentiated into immunomodulatory dendritic cells. Ex vivo crosslinking of human gingival tissue increased stiffness and reduced the production of inflammatory cytokines. Gingival mechano-immune regulation offers a novel approach to biomaterial-based treatments for periodontitis.

How dynamic circadian rhythms arise from a relatively static nuclear architecture remains a fundamental open question. Here, we identify the SWI/SNF chromatin-remodeling complex as a critical interface between the circadian clock and nuclear organization. Using endogenously tagged Moira (MOR), a core component of the Drosophila SWI/SNF complex and homolog of human BAF155, we find that MOR assembles into a small number of discrete foci near the nuclear periphery, in stark contrast to the current model of diffuse nuclear distribution for SWI/SNF-family proteins. We demonstrate that this localization is maintained by the inner nuclear envelope LEM-domain protein Otefin, effectively shifting MOR from a global to a localized regulator of chromatin architecture. DNA-FISH reveals that clock-regulated genes cluster into peripheral “hubs” that co-localize with MOR foci throughout the circadian cycle. ATAC-seq analysis shows that while MOR modulates chromatin accessibility genome-wide, it establishes a constitutive restrictive baseline specifically at clock-regulated loci. As a result, MOR depletion abolishes accessibility rhythms at these loci, rendering them constitutively hyper-accessible. This deregulation disrupts rhythmic gene expression and ultimately drives behavioral arrhythmia. Strikingly, oscillations of the core clock proteins PER and TIM remain intact, indicating that MOR loss uncouples the protein oscillator from its genomic output. Together, these results reveal that MOR-containing SWI/SNF foci form a stable perinuclear scaffold that gates chromatin accessibility, enabling the core clock machinery to convert transient protein oscillations into high-amplitude transcriptional rhythms.Significance StatementHow dynamic circadian rhythms emerge from a relatively static nuclear architecture remains a fundamental mystery. Here, we challenge the assumption that clock-target genes are randomly distributed by identifying a precise nuclear organization where these genes cluster into peripheral hubs. These hubs co-localize with stable SWI/SNF (MOR) foci anchored at the nuclear envelope. We demonstrate that this perinuclear scaffold is essential for gating rhythmic chromatin accessibility. Most importantly, loss of this architecture uncouples robustly oscillating clock protein program from its genomic and behavioral outputs. These findings reveal that circadian timekeeping is not merely a biochemical process but a spatially organized one, where nuclear topology licenses the translation of time into circadian rhythms.

Lipidation as a post-translational code for protein liquid-liquid phase separation.

A role for long-lived nuclear envelope proteins in cardiac ageing.

First report of two cultured mesomycetozoean isolates from Ostrea denselamellosa on the west coast of South Korea: phylogeny, development, and temperature-salinity responses.

BPS2026 – High-speed multiplexed DNA-paint imaging of nuclear organization using an expanded sequence repertoire

Polyploid cisplatin-resistant cancer cells have altered nuclear organization and epigenomic status.

Oncometabolite D-2-hydroxyglutarate regulates actin dynamics and nuclear homeostasis in IDH1-mutant glioma.

The 3D organization of the nucleus is crucial for maintaining cellular homeostasis and function, and it is dynamically regulated by both internal and external forces. Here, we investigate how material-induced cell deformation-generated by engineered micropatterned substrates-influences nuclear morphology and chromatin condensation in adipose-derived stem cells (ASCs). Using a multiscale approach that integrates mechanical modeling, atomic force microscopy (AFM), confocal imaging, and high-resolution analysis, we show that the surface micropatterning modulates intracellular force distributions, which in turn reshape the nuclear envelope and alter chromatin organization. Finite Element simulations reveal that distinct deformation profiles lead to region-specific mechanical stress across the nuclear envelope. These mechanical cues correlate with local chromatin decondensation, as demonstrated by 3D chromatin reconstructions and quantitative morphometric analyses. Our findings demonstrate that cell mechanical perturbations imposed by single-cell micropatterning can shape chromatin architecture and chromosome inter-distances. This opens new avenues for understanding mechanogenomic regulation and designing biomaterials that harness physical cues to control cell behavior.

The purpose of the work is to consider state corporations as subjects of state control and supervision. The emphasis is placed on the fact that currently only Rosatom and Roscosmos are endowed with such functions, although the law does not restrict the right of other corporations to do so. The author analyzes the current legislation regulating the organization and conduct of control and supervisory activities named by the state corporation. In addition, an analysis of the results of state control and supervision was carried out. It is concluded that the lack of scheduled inspections of licensees of space activities leads to the fact that control over compliance with licensing requirements is significantly weakened. As a result, there is a risk that potential violations may go unnoticed. This, in turn, calls into question the effectiveness of the state licensing and control system and may lead to failure to achieve the key indicator. The high efficiency of state control and supervision by the Rosatom State Corporation is noted, especially for the construction and reconstruction of facilities of federal nuclear organizations. It is concluded that it is necessary to carry out scheduled inspections in the field of compliance with licensing requirements for space activities.

Quiescence is a reversible, non-proliferative cellular state that enables survival under nutrient limitation while preserving the capacity to resume growth. Rather than representing a passive default, quiescence is an actively regulated program conserved from unicellular eukaryotes to metazoans. This review focuses on the nuclear mechanisms underlying quiescence entry, maintenance, and exit, with primary emphasis on mechanistic insights from yeast models while highlighting conserved principles in multicellular systems. Across species, quiescence is characterized by global transcriptional repression, chromatin compaction, and the extensive reorganization of nuclear architecture, coordinated by nutrient-sensing pathways centered on TOR/mTOR signaling. We discuss how transcriptional reprogramming is achieved through redistribution of RNA polymerases, dynamic transcription factor activities, and large-scale remodeling of histone modifications, alongside repressive chromatin formation. In parallel, post-transcriptional mechanisms-including intron retention, alternative polyadenylation, and accumulation of non-coding RNAs-fine-tune gene expression while limiting biosynthetic output. We further examine how changes in nuclear organization, such as nucleolar condensation, condensin-mediated chromosome rearrangements, and telomere hyperclusters, support long-term viability and genome stability. Collectively, this review highlights nuclear dynamics as an integrative regulatory layer that links metabolic state to cellular identity, adaptability, and long-term survival, with broad implications for development, stem cell function, and disease.

The nucleus, as the largest organelle within the cell, serves as the central hub for storing, replicating, and transcribing genetic information, thereby orchestrating vital cellular processes. In eukaryotic cells, the nuclear membrane is composed of several structural components: the outer and inner nuclear membranes, the nuclear pore complexes, and the underlying nuclear lamina, which together preserve the stability of the intracellular environment. Neurodegenerative disorders, such as Alzheimer's disease and related dementias, are characterized by the gradual degeneration and loss of neuronal structure and function in the central nervous system. Growing evidence suggests that alterations in nuclear envelope architecture are closely associated with the onset and progression of these diseases. This article summarizes the information, focusing on the regulators of the cell nuclear membrane, as well as its pathophysiological processes and regulatory mechanisms in neurodegenerative diseases. Moreover, this paper discusses related research advances that provide novel insights into a deeper understanding of the nuclear membrane in disease progression and its potential as a therapeutic target.

Probabilistic risk assessment (PRA) has emerged as a cornerstone of nuclear safety governance, providing a quantitative basis for evaluating accident likelihoods and potential consequences across multiple initiating events and system failures. As Ghana advances through Phase II of the International Atomic Energy Agency (IAEA) Milestones Approach, this study proposes a phased, Ghana-specific roadmap for embedding PRA into national licensing, inspection, and operational frameworks. A comparative evaluation of established programs in the United States, South Korea, Canada, and Finland demonstrates transferable practices in quantifying core damage frequency (CDF), large early release frequency (LERF), and severe accident progression. Benchmark targets—CDF <1.0 × 10−4/reactor year (ry) and LERF < 1.0 × 10−5/ry—are adopted as reference points for Ghana’s regulatory thresholds. Ghana’s baseline capacity reveals not only strengths in statutory authority and IAEA-supported training but also persistent gaps in modeling infrastructure, skilled analysts, and curated data systems. The proposed roadmap (2025–2035) outlines three implementation phases: (1) foundation building through staff certification, training curricula, and software acquisition; (2) pilot applications in vendor licensing and regulatory decision making; and (3) full-scale deployment of living probabilistic safety assessment integrated into oversight and operational risk monitoring. Quantitatively, the framework indicates potential to reduce inspection frequency for low-risk systems by up to 30% and optimize emergency planning zones by ~15% without compromising safety margins. This work contributes uniquely by (1) developing the first Ghana-specific PRA roadmap explicitly sequenced to Phase II of the IAEA Milestones Approach; (2) operationalizing institutional phasing through clear allocation of roles, deliverables, and auditable milestones for the Ghana Nuclear Regulatory Authority, Ghana Nuclear Power Program Organization, Nuclear Power Ghana and academia; and (3) proposing a phased tool adoption and regional interoperability strategy to ensure Ghana’s PRA practice is both resource realistic and globally benchmarked. These contributions distinguish the study from prior surveys, positioning it as a reproducible research framework for nuclear newcomer countries.