Nuclear Organization Research Articles

Evidence of oceanic and atmospheric tides in underwater ambient noise time records

Multiyear time records of low-frequency ocean ambient noise show clear evidence of a modulating influence by major semi-diurnal and diurnal gravitational tides. These are displayed by means of a variance spectral analysis of noise time records obtained from the United Nations Comprehensive Nuclear Test Ban Treaty Organization for hydrophone stations at Wake Island, Ascension Island and Diego Garcia. Narrow-band noise frequencies ranged from ½ to 10 Hz. There is also evidence in the noise records of a diurnal atmospheric tide related to solar radiation and atmospheric loading. This same tidal presence is seen in wind speed records as well. Part of the challenge in the analysis is to distinguish between expected diurnal behavior in wind speed, with its accompanying effect on ambient noise, and the presence of actual tidal lines. A brief history of earlier observations of diurnal variation in underwater acoustics is presented, along with some suggestions of causal mechanisms.

Basin scale propagation modeling of MLS signals from the Kauai Beacon source

Long distance underwater acoustic propagation is of interest for a variety of applications including underwater navigation, yet modeling such propagation is challenging due to the large degree of environmental uncertainty. In this presentation, the propagation of 75Hz center frequency maximum length sequence (MLS) signals emitted from a submerged source near Kauai and received at various sites throughout the Pacific Ocean Basin is modeled with the Bellhop ray tracing [1] and Monterey-Newport Parabolic Equation [2] models. Sites such as the Monterey Accelerated Research System (MARS) observatory and the Comprehensive Nuclear Test Ban Organization (CTBTO) hydroacoustic monitoring station near Wake Island are included in the discussion. The range-dependent environment is based on historical profiles from the World Ocean Atlas database and reanalysis data from the hybrid coordinate ocean model (HYCOM) [3]. Bathymetry profiles along the axis of propagation are interpolated from the General Bathymetric Chart of the Oceans (GEBCO) 2021 database [4]. Simulated broadband channel impulse responses transmission loss levels in the modeled environment are compared to selected receptions of the signal at the hydrophone sites. Additionally, fluctuations of the modeled transmission loss in the presence of an internal wave model [5] are discussed.

Towards unraveling the origins of eukaryotic nuclear genome organization.

With 3D genome mapping maturing over the past decade, studies exposed the differences between eukaryotic and prokaryotic genome organization. This raises the question of how the complex eukaryotic genome organization originated. Here, I explore potential pathways to answering this question, guided by our changing understanding of the origins of eukaryotes.

First person – Antoine Canat

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Antoine Canat is first author on ‘ DAXX safeguards heterochromatin formation in embryonic stem cells’, published in JCS. Antoine conducted the research described in this article while a PhD student in Emmanuelle Fabre's lab at Insitut de Recherche St Louis, Université de Paris, France. He is now a postdoc in the lab of Maria-Elena Torres-Padilla at the Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, Munich, Germany, investigating nuclear organization and chromatin regulation during totipotency and pluripotency.

Nuclear Phenotype and Heterochromatin Percentages in Somatic Cells on Five Species of Crotalaria L.

Crotalaria L. is a genus of flowering plants in the family Fabaceae (subfamily Faboideae). Mitotic index is proportionately relevant to cell division rate; mitotic index was found higher (10.38±1.08%) in C. spectabilis and lower (9.43±0.304%) in C. juncea. The nuclear organizations were observed chromocentric in all examined species. The interphase chromosome volume was highest in C. juncea (0.596±0.27 µ³ in meristematic cell and 0.408±0.21 µ³ in differentiated cell) and lowest in C. saltiana (0.205±0.31 µ³ in meristematic cell and 0.16±0.25 µ³ in differentiated cell) which do not correlated with the somatic chromosome number but may be related with environmental condition. The largest cell size was found in C. juncea (20.47±0.49 µm2 in meristematic cell and 106.47±0.63 µm2 in differentiated cell) and the smallest in C. saltiana (14.43±0.39 µm2 in meristematic cell and 45.86±0.21 µm2 in differentiated cell). It was also observed that, the mean value of cell size was larger in differentiated cell compared to meristematic cell in all the studied species of Crotalaria. Chromocenter numbers were found highest (13.66±0.14) in C. saltiana and lowest (9.50±0.32) in C. juncea which are considered as more primitive and more advance in nature, respectively. Percentages of heterochromatin per nuclear area were found highest (14.75±0.71) in C. saltiana and lowest (9.67±0.71) in C. juncea which are considered as more primitive and more advance in nature, respectively. J. Bio-Sci. 30(2): 79-88, 2022

Direct recruitment of Mis18 to interphase spindle pole bodies promotes CENP-A chromatin assembly

CENP-A chromatin specifies mammalian centromere identity, and its chaperone HJURP replenishes CENP-A when recruited by the Mis18 complex (Mis18C) via M18BP1/KNL2 to CENP-C at kinetochores during interphase. However, the Mis18C recruitment mechanism remains unresolved in species lacking M18BP1, such as fission yeast. Fission yeast centromeres cluster at G2 spindle pole bodies (SPBs) when CENP-ACnp1 is replenished and where Mis18C also localizes. We show that SPBs play an unexpected role in concentrating Mis18C near centromeres through the recruitment of Mis18 by direct binding to the major SPB linker of nucleoskeleton and cytoskeleton (LINC) component Sad1. Mis18C recruitment by Sad1 is important for CENP-ACnp1 chromatin establishment and acts in parallel with a CENP-C-mediated Mis18C recruitment pathway to maintain centromeric CENP-ACnp1 but operates independently of Sad1-mediated centromere clustering. SPBs therefore provide a non-chromosomal scaffold for both Mis18C recruitment and centromere clustering during G2. This centromere-independent Mis18-SPB recruitment provides a mechanism that governs de novo CENP-ACnp1 chromatin assembly by the proximity of appropriate sequences to SPBs and highlights how nuclear spatial organization influences centromere identity.

Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration.

Nuclear pore complexes (NPCs) play a critical role in maintaining the equilibrium between the nucleus and cytoplasm, enabling bidirectional transport across the nuclear envelope, and are essential for proper nuclear organization and gene regulation. Perturbations in the regulatory mechanisms governing NPCs and nuclear envelope homeostasis have been implicated in the pathogenesis of several neurodegenerative diseases. The ESCRT-III pathway emerges as a critical player in the surveillance and preservation of well-assembled, functional NPCs, as well as nuclear envelope sealing. Recent studies have provided insights into the involvement of nuclear ESCRT-III in the selective reduction of specific nucleoporins associated with neurodegenerative pathologies. Thus, maintaining quality control of the nuclear envelope and NPCs represents a pivotal element in the pathological cascade leading to neurodegenerative diseases. This review describes the constituents of the nuclear-cytoplasmic transport machinery, encompassing the nuclear envelope, NPC, and ESCRT proteins, and how their structural and functional alterations contribute to the development of neurodegenerative diseases.

You are who your friends are-nuclear pore proteins as components of chromatin-binding complexes.

Nuclear pore complexes are large multicomponent protein complexes that are embedded in the nuclear envelope, where they mediate nucleocytoplasmic transport. In addition to supporting transport, nuclear pore components, termed nucleoporins (Nups), can interact with chromatin and influence genome function. A subset of Nups can also localize to the nuclear interior and bind chromatin intranuclearly, providing an opportunity to investigate chromatin-associated functions of Nups outside of the transport context. This review focuses on the gene regulatory functions of such intranuclear Nups, with a particular emphasis on their identity as components of several chromatin regulatory complexes. Recent proteomic screens have identified Nups as interacting partners of active and repressive epigenetic machinery, architectural proteins, and DNA replication complexes, providing insight into molecular mechanisms via which Nups regulate gene expression programs. This review summarizes these interactions and discusses their potential functions in the broader framework of nuclear genome organization.

Performance assessment of a generic repository in salt host rock based on Task F of DECOVALEX-2023 – BASE's lessons learnt and future work

Abstract. The evaluation of coupled effects of mechanical deformation, fluid and gas flow, thermal loading, and chemical reactions is an important element of the performance and safety assessment of disposal systems for high-level radioactive waste and spent nuclear fuel in deep geological formations. Early investigations showed that to be able to conduct such an evaluation there was a need to enhance process understanding and to develop models capable of simulating coupled thermal–hydro–chemical–mechanical processes over relevant timescales and spatial scales. Recognising these challenges and needs, the DECOVALEX (DEvelopment of COupled models and their VALidation against Experiments) (https://decovalex.org, last access: 24 July 2023) was initiated in 1992 as an international cooperative project of nuclear waste organisations. BASE is one of the funding organisations for the current phase of DECOVALEX-2023 (running from 2020 to 2023) and actively contributes to Task F of the project (https://www.base.bund.de/DE/themen/fa/soa/projekte-aktuell/projekte-aktuell_node.html, last access: 24 July 2023, – “Beteiligung an der internationalen Forschungskooperation DECOVALEX”). Task F (https://www.decovalex.org/D-2023/task-f.html, last access: 24 July 2023) of DECOVALEX seeks to build confidence in the models, methods, and software used for performance assessment of deep geologic repositories and to highlight additional research and development needed to improve performance assessment methodologies. The task focuses on two illustrative disposal concepts for spent nuclear fuel: a generic repository in a fractured crystalline host rock and a generic repository in a salt formation. For each of the disposal concepts a reference case is defined that includes a set of conceptual models and parameters describing features, events, and processes that impact repository performance. Modelling teams work independently and are responsible for determining how best to implement and couple the models. Each team develops its own model(s), calculates agreed performance indicator values, and performs uncertainty and sensitivity analysis. The comparison of model results is conducted in stages, commencing with a comparison of key outputs of individual process models, followed by a comparison of a single deterministic simulation of the full reference case, and proceeding to uncertainty and sensitivity analysis. The present contribution describes recent BASE activities within Task F Salt of DECOVALEX-2023. Lessons learnt are discussed and possible future steps are presented.

Historical contextualization of the site selection process for the German high-level nuclear waste (HLW) repository as a tool for information and awareness preservation

Abstract. It is always the same old story – after a couple of years most people cannot remember how decisions in nuclear waste disposal were made because many important documents are not available to the public as they have not been officially archived or are not accessible. This is why site selection Act § 6 requires nuclear waste organizations not only to store, but also to publish those documents. So, the Bundesgesellschaft für Endlagerung (BGE) provides information about all the relevant documents on the BGE website (https://www.bge.de/de/endlagersuche/wesentliche-unterlagen/, last access: 25 July 2023) and gives them to the Federal Office for the Safety of Nuclear Waste Management (BASE), which publishes them on the following website: https://www.endlagersuche-infoplattform.de/webs/Endlagersuche/DE/_home/home_node.html (last access: 25 July 2023). For the siting process, the BGE knowledge management works on methods to keep the relevant information at least for the next generation – as a first step in the process of long-term preservation, which is the task of the BASE. When we set up the historical contextualization project, our idea was not only to create an archive platform of the relevant BGE-internal and BGE-external documents on the siting process such as papers, letters, minutes, files, logs, and geological data, but also to show how the documents relate to each other. In order to do this, we had to take the historical background into account. At first, we began exclusively with the files and the eyewitness accounts of our site selection department, but we became increasingly aware that we also have to consider the interactions between all stakeholders involved in the site selection procedure. The presentation will show techniques and examples of how all information from documents, eye witnesses, and other sources can be saved and related to each other in order to understand how and why decisions have developed in a certain direction. A set of cohesive storylines, central documents, and oral history methods taken from contemporary historical research forms the background for this historical contextualization. A storyline consists of chronological actions in a certain topic, e.g. the writing of the sub-areas' interim report. The most important actions that are part of the storylines are related to the most important documents. Oral history methods are used for interviews with eyewitnesses to elicit their tacit knowledge and to reflect on the historical background and their emotions. The aim is not to create documentation from the BGE's perspective only, but also to collect a variety of perspectives as reservoirs of information for future historians, who can create a broader historical image from them. Another goal is to keep an open mind with regard to the multidisciplinary and transdisciplinary approaches of future social scientists.

Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1-aging and epigenomics.

Much recent attention has been directed toward the spatial organization of the cell nucleus and the manner in which three-dimensional topologically associated domains and transcription factories are epigenetically coordinated to precisely bring enhancers into close proximity with promoters to control gene expression. Twenty lines of evidence robustly implicate cannabinoid exposure with accelerated organismal and cellular aging. Aging has recently been shown to be caused by increased DNA breaks. These breaks rearrange and maldistribute the epigenomic machinery to weaken and reverse cellular differentiation, cause genome-wide DNA demethylation, reduce gene transcription, and lead to the inhibition of developmental pathways, which contribute to the progressive loss of function and chronic immune stimulation that characterize cellular aging. Both cell lineage-defining superenhancers and the superanchors that control them are weakened. Cannabis exposure phenocopies the elements of this process and reproduces DNA and chromatin breakages, reduces the DNA, RNA protein and histone synthesis, interferes with the epigenomic machinery controlling both DNA and histone modifications, induces general DNA hypomethylation, and epigenomically disrupts both the critical boundary elements and the cohesin motors that create chromatin loops. This pattern of widespread interference with developmental programs and relative cellular dedifferentiation (which is pro-oncogenic) is reinforced by cannabinoid impairment of intermediate metabolism (which locks in the stem cell-like hyper-replicative state) and cannabinoid immune stimulation (which perpetuates and increases aging and senescence programs, DNA damage, DNA hypomethylation, genomic instability, and oncogenesis), which together account for the diverse pattern of teratologic and carcinogenic outcomes reported in recent large epidemiologic studies in Europe, the USA, and elsewhere. It also accounts for the prominent aging phenotype observed clinically in long-term cannabis use disorder and the 20 characteristics of aging that it manifests. Increasing daily cannabis use, increasing use in pregnancy, and exponential dose-response effects heighten the epidemiologic and clinical urgency of these findings. Together, these findings indicate that cannabinoid genotoxicity and epigenotoxicity are prominent features of cannabis dependence and strongly indicate coordinated multiomics investigations of cannabinoid genome-epigenome-transcriptome-metabolome, chromatin conformation, and 3D nuclear architecture. Considering the well-established exponential dose-response relationships, the diversity of cannabinoids, and the multigenerational nature of the implications, great caution is warranted in community cannabinoid penetration.

Understanding the regulator-regulatee relationship for developing safety culture.

Regulatory authorities in safety-critical industries typically seek to influence the safety culture of the organizations they oversee. However, we know little about how regulatory authorities achieve this influence (e.g., what roles are adopted, relationship characteristics) and, more generally, about how external actors shape an organization's safety culture. Using a qualitative design in the nuclear industry, we developed our conceptual and empirical understanding of the roles through which a regulator influences the safety culture of their regulated organizations and what characteristics within the regulator-regulatee relationship facilitate positive safety culture developments. Data were collected through interviews with inspectors from a nuclear regulator and employees of regulated nuclear organizations, and from an inspection of regulatory documents. The findings identified that the regulator was perceived to hold three complementary roles for safety culture development: being an enforcer, working as a partner (providing opportunities for licenseholders to improve beyond compliance), and acting as an advisor to regulated organizations. Analysis also showed that effective relationships in these roles, and which were central to influencing safety culture, were perceived to be characterized by professionalism, transparency, and balance between formal enforcement and informal exchange. Theoretical implications to advance conceptualizations of safety culture as well as practical implications for risk regulators are discussed.

Lamin B1 as a key modulator of the developing and aging brain.

Lamin B1 is an essential protein of the nuclear lamina that plays a crucial role in nuclear function and organization. It has been demonstrated that lamin B1 is essential for organogenesis and particularly brain development. The important role of lamin B1 in physiological brain development and aging has only recently been at the epicenter of attention and is yet to be fully elucidated. Regarding the development of brain, glial cells that have long been considered as supporting cells to neurons have overturned this representation and current findings have displayed their active roles in neurogenesis and cerebral development. Although lamin B1 has increased levels during the differentiation of the brain cells, during aging these levels drop leading to senescent phenotypes and inciting neurodegenerative disorders such as Alzheimer's and Parkinson's disease. On the other hand, overexpression of lamin B1 leads to the adult-onset neurodegenerative disease known as Autosomal Dominant Leukodystrophy. This review aims at highlighting the importance of balancing lamin B1 levels in glial cells and neurons from brain development to aging.

Exploring ‘Accommodation’ to Understand the Behaviour of Rising Powers in the Global Nuclear Order: The Cases of India and Brazil

ABSTRACT First put forth by Hedley Bull in the 1970s, the notion of ‘accommodation’ is an often-neglected approach to understanding the role, rights and responsibilities of emerging nuclear powers from the Global South in the nuclear order. The existing literature looks at the avenues and conditions through which the institutions of the nuclear order grant accommodation. However, analysis of the demands raised by rising powers at various stages of the nuclear order's development is severely lacking. The cases of India and Brazil, two rising powers with advanced nuclear capabilities, highlight some of the demands of accommodation raised by these states during the early development of the Nuclear Non-proliferation Treaty (NPT) – a cornerstone agreement in the global nuclear architecture. Two important demands – namely, regional security considerations in the global system and the adoption of the principle of mutual obligations and responsibilities – have shaped these states’ behaviour vis-à-vis the NPT.

Recruitment of the Histone Variant MacroH2A1 to the Pericentric Region Occurs upon Chromatin Relaxation and Is Responsible for Major Satellite Transcriptional Regulation.

Heterochromatin formation plays a pivotal role in regulating chromatin organization and influences nuclear architecture and genome stability and expression. Amongst the locations where heterochromatin is found, the pericentric regions have the capability to attract the histone variant macroH2A1. However, the factors and mechanisms behind macroH2A1 incorporation into these regions have not been explored. In this study, we probe different conditions that lead to the recruitment of macroH2A1 to pericentromeric regions and elucidate its underlying functions. Through experiments conducted on murine fibroblastic cells, we determine that partial chromatin relaxation resulting from DNA damage, senescence, or histone hyper-acetylation is necessary for the recruitment of macroH2A1 to pericentric regions. Furthermore, macroH2A1 is required for upregulation of noncoding pericentric RNA expression but not for pericentric chromatin organization. Our findings shed light on the functional rather than structural significance of macroH2A1 incorporation into pericentric chromatin.

Crosstalk between chromatin, chromosomes, and epigenetics.

The International Asilomar Chromatin, Chromosomes, and Epigenetics Conference was held online from 8 to 10 December 2022. Topics of this year's conference included chromosome dysregulation, genome integrity, nuclear organization, regulation of chromatin, epigenetics, transcription, and gene regulation in cell differentiation and disease. The meeting featured four keynote speakers, including Yamini Dalal (National Cancer Institute, USA), Meaghan Jones (University of Manitoba, Canada), Pedro Rocha (National Institute of Child Health and Human Development, USA), and Vincent Pasque (University of Leuven, Belgium). The meeting brought together scientists at all career stages to present and discuss their work in the fields of chromatin and epigenetics.

Nucleolar structure connects with global nuclear organization.

The nucleolus is a multifunctional nuclear body. To tease out the roles of nucleolar structure without resorting to the use of multi-action drugs, we knocked down the RNA polymerase I subunit RPA194 in HeLa cells by siRNA. Loss of RPA194 resulted in nucleolar-structural segregation and effects on both nucleolus-proximal and distal-nuclear components. The perinucleolar compartment was disrupted, centromere clustering around nucleoli was significantly reduced, and the intranuclear locations of specific genomic loci were altered. Moreover, Cajal bodies, distal from nucleoli, underwent morphological and some compositional changes. In comparison, when the preribosomal RNA-processing factor, UTP4, was knocked down, neither nucleolar segregation nor the intranuclear effects were observed, demonstrating that the changes of nucleolar proximal and distal nuclear domains in RPA194 knockdown cells unlikely arise from a cessation of ribosome synthesis, rather from the consequence of nucleolar-structure alteration. These findings point to a commutative system that links nucleolar structure to the maintenance and spatial organization of certain nuclear domains and genomic loci.

Arabidopsis thaliana Subclass I ACTIN DEPOLYMERIZING FACTORs Regulate Nuclear Organization andGene Expression.

ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein that regulates the organization and dynamics of actin microfilaments. Eleven ADFs in the Arabidopsis thaliana genome are grouped into four subclasses, and subclass I ADFs, ADF1-4, are all expressed throughout the plant. Previously, we showed that subclass I ADFs function in the regulation of the response against powdery mildew fungus as well as in the regulation of cell size and endoreplication. Here, we report a new role of subclass I ADFs in the regulation of nuclear organization and gene expression. Through microscopic observation of epidermal cells in mature leaves, we found that the size of chromocenters in both adf4 and transgenic lines where expression of subclass I ADFs is downregulated (ADF1-4Ri) was reduced compared with that of wild-type Col-0. Arabidopsis thaliana possesses eight ACTIN (ACT) genes, among which ACT2, -7 and -8 are expressed in vegetative organs. The chromocenter size in act7, but not in the act2/8 double mutant, was enlarged compared with that in Col-0. Microarray analysis revealed that 1,818 genes were differentially expressed in adf4 and ADF1-4Ri. In particular, expression of 22 nucleotide-binding leucine-rich repeat genes, which are involved in effector-triggered plant immunity, was reduced in adf4 and ADF1-4Ri. qRT-PCR confirmed the altered expressions shown with microarray analysis. Overall, these results suggest that ADF regulates various aspects of plant physiology through its role in regulation of nuclear organization and gene expression. The mechanism how ADF and ACT regulate nuclear organization and gene expression is discussed.

Nuclear damage in LMNA mutant iPSC-derived cardiomyocytes is associated with impaired lamin localization to the nuclear envelope.

The LMNA gene encodes the nuclear envelope proteins Lamins A and C, which comprise a major part of the nuclear lamina, provide mechanical support to the nucleus, and participate in diverse intracellular signaling. LMNA mutations give rise to a collection of diseases called laminopathies, including dilated cardiomyopathy (LMNA-DCM) and muscular dystrophies. Although nuclear deformities are a hallmark of LMNA-DCM, the role of nuclear abnormalities in the pathogenesis of LMNA-DCM remains incompletely understood. Using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LMNA mutant patients and healthy controls, we show that LMNA mutant iPSC-CM nuclei have altered shape or increased size compared to healthy control iPSC-CM nuclei. The LMNA mutation exhibiting the most severe nuclear deformities, R249Q, additionally caused reduced nuclear stiffness and increased nuclear fragility. Importantly, for all cell lines, the degree of nuclear abnormalities corresponded to the degree of Lamin A/C and Lamin B1 mislocalization from the nuclear envelope. The mislocalization was likely due to altered assembly of Lamin A/C. Collectively, these results point to the importance of correct lamin assembly at the nuclear envelope in providing mechanical stability to the nucleus and suggest that defects in nuclear lamina organization may contribute to the nuclear and cellular dysfunction in LMNA-DCM.

Mycorrhizal response of Solanum tuberosum to homokaryotic versus dikaryotic arbuscular mycorrhizal fungi.

Arbuscular mycorrhizal fungi (AMF) are obligate plant symbionts of most land plants. In these organisms, thousands of nuclei that are either genetically similar (homokaryotic) or derived from two distinct parents (dikaryotic) co-exist in a large syncytium. Here, we investigated the impact of these two nuclear organizations on the mycorrhizal response of potatoes (Solanum tuberosum) by inoculating four potato cultivars with eight Rhizophagus irregularis strains individually (four homokaryotic and four dikaryotic). By evaluating plant and fungal fitness-related traits four months post inoculation, we found that AMF genetic organization significantly affects the mycorrhizal response of host plants. Specifically, homokaryotic strains lead to higher total, shoot, and tuber biomass and a higher number of tubers, compared to dikaryotic strains. However, fungal fitness-related traits showed no clear differences between homokaryotic and dikaryotic strains. Nucleotype content analysis of single spores confirmed that the nucleotype ratio of AMF heterokaryon spores can shift depending on host identity. Together, these findings continue to highlight significant ecological differences derived from the two distinct genetic organizations in AMF.