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Upregulation of nuclear factor κB (NFκB) signaling is a hallmark of aging and a major cause of age‐related chronic inflammation. However, its effect on cellular senescence remains unclear. Here, we show that alteration of NFκB nuclear dynamics from oscillatory to sustained by depleting a negative feedback regulator of NFκB pathway, NFκB inhibitor alpha (IκBα), in the presence of tumor necrosis factor α (TNFα) promotes cellular senescence. Sustained NFκB activity enhanced inflammatory gene expression through increased NFκB‐DNA binding and slowed the cell cycle. IκBα protein was decreased under replicative or oxidative stress in vitro. Furthermore, a decrease in IκBα protein and an increase in DNA‐NFκB binding at the transcription start sites of age‐associated genes in aged mouse hearts suggested that nuclear NFκB dynamics may play a critical role in the progression of aging. Our study suggests that nuclear NFκB dynamics‐dependent epigenetic changes regulated over time in a living system, possibly through a decrease in IκBα, enhance the expression of inflammatory genes to advance the cells to a senescent state. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal fungi (AMF) are obligate mutualists that can enhance nutrition and growth of their plant hosts while providing protection against pathogens. AMF produce spores and hyphal networks that can carry thousands of nuclei in a continuous cytoplasm, with no evidence of sexual reproduction. This review examines the impact of genomic technologies on our view of AMF genetics and evolution. We highlight how the genetics, nuclear dynamics, and epigenetics of these prominent symbionts follow trends preserved in distant multinucleate fungal relatives. We also propose new avenues of research to improve our understanding of their nuclear biology and their intricate genetic interactions with plant hosts. [ABSTRACT FROM AUTHOR]

The DNA replication process needs to be coordinated with other DNA metabolism transactions and must eventually extend to the full genome, regardless of chromatin status, gene expression, secondary structures and DNA lesions. Completeness and accuracy of DNA replication are crucial to maintain genome integrity, limiting transformation in normal cells and offering targeting opportunities for proliferating cancer cells. DNA replication is thus tightly coordinated with chromatin dynamics and 3D genome architecture, and we are only beginning to understand the underlying molecular mechanisms. While much has recently been discovered on how DNA replication initiation is organised and modulated in different genomic regions and nuclear territories—the so-called "DNA replication program"—we know much less on how the elongation of ongoing replication forks and particularly the response to replication obstacles is affected by the local nuclear organisation. Also, it is still elusive how specific components of nuclear architecture participate in the replication stress response. Here, we review known mechanisms and factors orchestrating replication initiation, and replication fork progression upon stress, focusing on recent evidence linking genome organisation and nuclear architecture with the cellular responses to replication interference, and highlighting open questions and future challenges to explore this exciting new avenue of research. [ABSTRACT FROM AUTHOR]

We describe nuclear effects in structure functions of nuclei in DIS by means of a multiplicative factor β A (x) which differentiates the structure function of the bound nucleons from that of the free nucleons. Our analysis determines that β A (x) establishes a relation between the quark-gluon dynamics expressed by the bound nucleon structure functions and the nuclear dynamics as described by the well-known semi-empirical Bethe-Weizsäcker mass formula. This relation corroborates a connection between the underlying quark-gluon dynamics and the phenomenological nuclear dynamics. [ABSTRACT FROM AUTHOR]

The hyperbolic matrix method for the treatment of atomic and molecular nuclear dynamics is derived by means of the wave packet technique within the Born–Oppenheimer approach formalism. This method allows one to calculate the evolution of a wave packet by means of the product of usual matrices instead of the time propagation of matrix exponentials. We provide a detailed description of this method, considering Tully’s model as an example. We also show good agreement with the Landau–Zener model application.

Non alloyed carbon deoxidation can fundamentally solve the technical difficulty of fatigue failure of high‐quality bearing steel caused by inclusions. Herein, nonalloyed carbon deoxidation is presented with CO as a product, which can avoid the problem of residual inclusions. The thermodynamic and kinetic nucleation models of [C] deoxidation are constructed. The results suggest that a decrease in pCO strengthens the deoxidation ability of [C], and the [%O] balanced with [%C] shows multiple decreases. When pCO = 0.1 atm and [%C] = 0.5%, [%O] can be reduced to less than 10 ppm. However, from the results of the nucleation kinetic model, as pCO decreases, the critical radius r* increases, and the resistance of CO nucleation also increases. This results in difficulty of nucleation. Based on the nucleation kinetic model, the following C–O reaction mechanism is proposed: 1) [C] and [O] move to the reaction interface, 2) [C] + [O] = CO, forming a critical bubble nucleus, and 3) the newly formed CO diffuses continuously into the critical bubble, causing the bubble to grow and float away. Alternatively, the CO separates from the gas–liquid interface and enters the bubble, which floats away. [ABSTRACT FROM AUTHOR]

The nuclear playground in Southern Asia is marked by an exceptional level of complexity. A number of players; their disparate thinking on how to establish deterrence; nuclear dyads that elongate into strategic chains; inter-twining of nuclear issues with conventional, space, cyber realms; disparities in military capabilities; historical animosities accentuated by unresolved territorial conflicts; divides that spawn ideologies, religions and civilizational issues; all make for an immensely complex situation. The consequent regional nuclear dynamics has fair potential for crisis and arms race instability. As a way to address the regional nuclear challenges, the paper explores the character of Pakistan–India and China–India nuclear dyads along three specific axes: drivers of conflict; points of commonalities, similarities and differences; and implications of these for their nuclear stockpiles. Armed with this understanding, it then offers some policy recommendations to address the concomitant dangers.

Strong-field induced valence electron excitation is a common process in strong field interaction with atoms and molecules. In the case of polyatomic molecules, the effects of ionization from low-lying molecular orbitals and nuclear dynamics during the interaction can play critical roles for electron excitation. In this work, we investigate the involved molecular orbitals in the electron excitation of singly ionized acetylene in a strong laser field using alignment dependence and laser intensity dependence. Additionally, the involved nuclear dynamics during the electron excitation are identified from the difference in the kinetic energy release and the angular distribution of laser-induced dissociation with different pulse durations and intensities. The laser intensity dependence clearly shows the relative strength change of two excitation pathways in the measured momentum and angle-resolved distributions.

We report a measurement of electron momentum distributions of valence orbitals of cyclopentene employing symmetric noncoplanar (e,2e) kinematics at impact energies of 1200 and 1600 eV plus the binding energy. Experimental momentum profiles for individual ionization bands are obtained and compared with theoretical calculations considering nuclear dynamics by harmonic analytical quantum mechanical and thermal sampling molecular dynamics approaches. The results demonstrate that molecular vibrational motions including ring-puckering of this flexible cyclic molecule have obvious influences on the electron momentum profiles for the outer valence orbitals, especially in the low momentum region. For π∗-like molecular orbitals 3a′′, 2a′′, and 3a′, the impact-energy dependence of the experimental momentum profiles indicates a distorted wave effect. [ABSTRACT FROM AUTHOR]

Pericentromeric heterochromatin is mostly composed of repetitive DNA sequences prone to aberrant recombination. Cells have developed highly specialized mechanisms to enable 'safe' homologous recombination (HR) repair while preventing aberrant recombination in this domain. Understanding heterochromatin repair responses is essential to understanding the critical mechanisms responsible for genome integrity and tumor suppression. Here, we review the tools, approaches, and methods currently available to investigate double-strand break (DSB) repair in pericentromeric regions, and also suggest how technologies recently developed for euchromatin repair studies can be adapted to characterize responses in heterochromatin. With this ever-growing toolkit, we are witnessing exciting progress in our understanding of how the 'dark matter' of the genome is repaired, greatly improving our understanding of genome stability mechanisms. [ABSTRACT FROM AUTHOR]

We analytically study quantum dissipative dynamics described by the Caldirola-Kanai model with inter-particle interactions. We have found that the dissipative quantum dynamics of the Caldirola-Kanai model can be exactly mapped to a dissipationless quantum dynamics under a negative external harmonic potential, even when the particles are strongly interacting. In particular, we show that the mapping is valid for the unitary Fermi gas, which is relevant for cold atoms and nuclear matters.

The eukaryotic nucleus shows organized structures of chromosomes, transcriptional components and their associated proteins. It has been believed that such a dense nuclear environment prevents the formation of a cytoskeleton-like network of protein filaments. However, accumulating evidence suggests that the cell nucleus also possesses structural filamentous components to support nuclear organization and compartments, which are referred to as nucleoskeleton proteins. Nucleoskeleton proteins including lamins and actin influence nuclear dynamics including transcriptional regulation, chromatin organization and DNA damage responses. Furthermore, these nucleoskeleton proteins play a pivotal role in cellular differentiation and animal development. In this commentary, we discuss how nucleoskeleton-based regulatory mechanisms orchestrate nuclear dynamics. [ABSTRACT FROM AUTHOR]

In this paper, we briefly review the studies on nuclear structure and nuclear dynamics using the Canonical-basis time-dependent Hartree-Fock-Bogoliubov (Cb-TDHFB) theory which is one of the time-dependent mean-field models which deal with nuclear pairing correlation. At first, after a brief introduction of the time-dependent mean-field models, we explain the derivation and the properties of Cb-TDHFB equations. Next, we introduce the methods to study the nuclear linear responses and to simulate the nuclear collision in terms of the time-dependent mean-field models. Then, we display parts of the results obtained by using the time-dependent methods; Strength functions of electric dipole (E1) excitation mode of 172Yb, Systematic study of low-energy E1 mode, and Comparison of the simulations of the fusion reactions using time-dependent mean-field models with and without pairing correlation. Finally, we summarize the Cb-TDHFB activities and discuss its perspectives.

Aging is a progressive functional decline in organs and tissues over time and typically represents the accumulation of psychological and social changes in a human being. Diverse diseases, such as cardiovascular, musculoskeletal, and neurodegenerative disorders, are now understood to be caused by aging. While biological assessment of aging mainly focuses on the gradual changes that occur either on the molecular scale, for example, alteration of gene expression and epigenetic modification, or on larger scales, for example, changes in muscle strength and cardiac function, the mechanics that regulates the behavior of individual cells and interactions between the internal elements of cells, are largely missing. In this study, we show that the dynamic features of migrating cells across different human ages could help to establish the underlying mechanism of biological age-dependent cellular functional decline. To determine the relationship between cellular dynamics and human age, we identify the characteristic relationship between cell migration and nuclear motion which is tightly regulated by nucleus-bound cytoskeletal organization. This analysis demonstrates that actomyosin contractility-dependent nuclear motion plays a key role in cell migration. We anticipate this study to provide noble biophysical insights on biological aging in order to precisely diagnose age-related chronic diseases.

Mechanical and physical stimuli including material stiffness and topography or applied mechanical strain have been demonstrated to modulate differentiation of glial progenitor and neural stem cells. Recent studies probing such mechanotransduction in oligodendrocytes have focused chiefly on the biomolecular components. However, the cell-level biophysical changes associated with such responses remain largely unknown. Here, we explored mechanotransduction in oligodendrocyte progenitor cells (OPCs) during the first 48 h of differentiation induction by quantifying the biophysical state in terms of nuclear dynamics, cytoskeleton organization, and cell migration. We compared these mechanophenotypic changes in OPCs exposed to both chemical cues (differentiation factors) and mechanical cues (static tensile strain of 10%) with those exposed to only those chemical cues. We observed that mechanical strain significantly hastened the dampening of nuclear fluctuations and decreased OPC migration, consistent with the progression of differentiation. Those biophysical changes were accompanied by increased production of the intracellular microtubule network. These observations provide insights into mechanisms by which mechanical strain of physiological magnitude could promote differentiation of progenitor cells to oligodendrocytes via inducing intracellular biophysical responses over hours to days post induction.

Mechanical and physical stimuli including material stiffness and topography or applied mechanical strain have been demonstrated to modulate differentiation of glial progenitor and neural stem cells. Recent studies probing such mechanotransduction in oligodendrocytes have focused chiefly on the biomolecular components. However, the cell-level biophysical changes associated with such responses remain largely unknown. Here, we explored mechanotransduction in oligodendrocyte progenitor cells (OPCs) during the first 48 h of differentiation induction by quantifying the biophysical state in terms of nuclear dynamics, cytoskeleton organization, and cell migration. We compared these mechanophenotypic changes in OPCs exposed to both chemical cues (differentiation factors) and mechanical cues (static tensile strain of 10%) with those exposed to only those chemical cues. We observed that mechanical strain significantly hastened the dampening of nuclear fluctuations and decreased OPC migration, consistent with the progression of differentiation. Those biophysical changes were accompanied by increased production of the intracellular microtubule network. These observations provide insights into mechanisms by which mechanical strain of physiological magnitude could promote differentiation of progenitor cells to oligodendrocytes via inducing intracellular biophysical responses over hours to days post induction. [ABSTRACT FROM AUTHOR]

[Display omitted] • Viruses can modulate intracellular microenvironments, including membraneless organelles (MLOs). • HIV-1 infection induces the formation of nuclear CPSF6 condensates. • HIV-1 capsid and CPSF6 coexist inside HIV-MLOs and probably trigger their formation. • HIV-1 induced MLOs play key functions in the early steps of the viral life cycle. Viruses are obligate parasites that rely on their host's cellular machinery for replication. To facilitate their replication cycle, many viruses have been shown to remodel the cellular architecture by inducing the formation of membraneless organelles (MLOs). Eukaryotic cells have evolved MLOs that are highly dynamic, self-organizing microenvironments that segregate biological processes and increase the efficiency of reactions by concentrating enzymes and substrates. In the context of viral infections, MLOs can be utilized by viruses to complete their replication cycle. This review focuses on the pathway used by the HIV-1 virus to remodel the nuclear landscape of its host, creating viral/host niches that enable efficient viral replication. Specifically, we discuss how the interaction between the HIV-1 capsid and the cellular factor CPSF6 triggers the formation of nuclear MLOs that support nuclear reverse transcription and viral integration in favored regions of the host chromatin. This review compiles current knowledge on the origin of nuclear HIV-MLOs and their role in early post-nuclear entry steps of the HIV-1 replication cycle. [ABSTRACT FROM AUTHOR]

To investigate the mitotic dynamics of an appressorium, we used live-cell confocal imaging of a fluorescence-based mitotic reporter strain of Magnaporthe oryzae . We present evidence that the M. oryzae appressorium remains viable and mitotically active well after host penetration. These results suggest the potential roles of the appressorium during post-penetration proliferation of invasive hyphae. Our studies also revealed that a mitotic appressorial nucleus undergoes extreme constriction and elongation as it migrates through the penetration peg in a manner analogous to mitosis during cell-to-cell movement of invasive hyphae. Understanding the mechanisms underlying these pathogen-specific nuclear dynamics may provide new targets for disease control. [ABSTRACT FROM AUTHOR]

The structural organization of the nucleus and its content has drawn increasing interest in recent years, as it is has become evident that the spatial and temporal arrangement of the genome and associated structures plays a crucial role in transcriptional regulation and numerous other functions. Shining light on the dynamic nature of this organization, along with the processes controlling it, were the topics of the Wenner-Gren Foundations international symposium "Nuclear Dynamics: Design (and) Principles." The meeting, organized by Piorgiogio Percipalle, Maria Vartiainen, Neus Visa, and Ann-Kristin Östlund-Farrants, brought over 60 participants, including 20 international speakers, to Stockholm, Sweden from August 19–22, 2015 to share the latest developments in the field. Given the unpublished nature of many of the talks, we have focused on covering the discussed topics and highlighting the latest trends in this exciting and rapidly evolving field. [ABSTRACT FROM PUBLISHER]

Cells sense physical cues at the level of focal adhesions and transduce them to the nucleus by biochemical and mechanical pathways. While the molecular intermediates in the mechanical links have been well studied, their dynamic coupling is poorly understood. In this study, fibroblast cells were adhered to micropillar arrays to probe correlations in the physical coupling between focal adhesions and nucleus. For this, we used novel imaging setup to simultaneously visualize micropillar deflections and EGFP labeled chromatin structure at high spatial and temporal resolution. We observed that micropillar deflections, depending on their relative positions, were positively or negatively correlated to nuclear and heterochromatin movements. Our results measuring the time scales between micropillar deflections and nucleus centroid displacement are suggestive of a strong elastic coupling that mediates differential force transmission to the nucleus. [ABSTRACT FROM AUTHOR]

Only a limited number of studies exist on the life cycles of nonmodel ciliates such as Chilodonella uncinata (Cl: Phyllopharyngea). The handful of papers on this taxon indicate the presence of a heteromeric macronucleus, marked by separate DNA-rich and DNA-poor regions. Here, we study the life cycle of C. uncinata using confocal laser scanning microscopy with 4′,6-diamidino-2-phenylindole staining, which allows us to differentiate nuclear dynamics of the micronucleus and the macronucleus during life-cycle stages. We photo-documented various stages and confirmed aspects of the development of the new macronucleus previously characterized by electron microscopy. We further reveal the heteromeric structure of the macronucleus with Z-stacks and three-dimensional (3D) reconstructions. We find no evidence for the presence of an endosome at the center of the macronucleus during vegetative growth. In addition to illustrating the life cycle of this ciliate, the approaches developed for this study will enable additional comparative analyses of nuclear dynamics using fluorescence microscopy. [ABSTRACT FROM AUTHOR]

DM1 (myotonic dystrophy type 1) is caused by elongation of a CTG repeat in the DMPK (dystrophia myotonica-protein kinase) gene. mRNA transcripts containing these CUGexp (CUG expansion) repeats form accumulations, or foci, in the nucleus of the cell. The pathogenesis of DM1 is proposed to result from inappropriate patterns of alternative splicing caused by sequestration of the developmentally regulated alternative splicing factor MBNL1 (muscleblind-like 1) by these foci. Since eye lens cataract is a common feature of DM1 we have examined the distribution and dynamics of MBNL1 in lens epithelial cell lines derived from patients with DM1. The results of the present study demonstrate that only a small proportion of nuclear MBNL1 accumulates in CUGexp pre-mRNA foci. MBNL1 is, however, highly mobile and changes localization in response to altered transcription and splicing activity. Moreover, immunolocalization studies in lens sections suggest that a change in MBNL1 distribution is important during lens growth and differentiation. Although these data suggest that the loss of MBNL1 function due to accumulation in foci is an unlikely explanation for DM1 symptoms in the lens, they do demonstrate a strong relationship between the subcellular MBNL1 localization and pathways of cellular differentiation, providing an insight into the sensitivity of the lens to changes in MBNL1 distribution. [ABSTRACT FROM AUTHOR]

Abstract: We summarize our development of instrumentation for the study of liquids, aqueous solutions, and liquid/solid interfaces using resonant inelastic soft X-ray scattering (RIXS) and illustrate the value of the experimental approach with a few instructional examples. Using a high-transmission, high-resolution soft X-ray spectrometer, we are able to measure complete RIXS maps, i.e., record the soft X-ray emission intensity as a function of emission and absorption energy. As a first example, we show that a comparison of RIXS maps of “normal” and deuterated liquid and gas-phase water allows us to identify dissociation processes on the time scale of the oxygen 1 s core-hole lifetime. Similar dissociation effects are found for aqueous solutions of ammonia and amino acids. For the latter, the pH value has a strong influence on the nitrogen K emission spectra, which can thus be used to identify protonation and deprotonation processes in the solution. Finally, we review the investigation of the interface between liquid water and a CuIn(S,Se)2 thin-film solar cell absorber, demonstrating the power of the technique to study liquid–solid interfaces in real-world systems. Under X-ray irradiation, the formation of sulfate on the absorber surface can be found. [Copyright &y& Elsevier]

Abstract: Ultrafast dissociation following core–shell excitation into an antibonding orbital led to the early observation in HBr of atomic Auger lines associated to the decay of dissociated excited atoms. The purpose of this article is to review the very large variety of systems where such a situation has been encountered, extending from simple diatomic molecules toward more complex systems like polyatomics, clusters, or adsorbed molecules. Interestingly, this phenomenon has revealed an extremely rich and powerful tool for probing nuclear dynamics and its subtle interplay with electron relaxation occurring on a comparable time scale. Consequently this review covers a surprisingly large period, starting in 1986 and still ongoing. [Copyright &y& Elsevier]

This study focuses on the two C1s-to-LUMO (lowest unoccupied molecular orbital) excitations of the iso-dichloroethylene (H2C=CCl2) and the subsequent Auger decay. We investigate the effect of the two different carbon core excitations on the population of the cation produced after electronic relaxation. The resonant Auger spectra are interpreted by comparison to the valence shells photoionization spectrum and with the help of theoretical calculations. Several consequences of the core-hole localization on the electronic decay are observed. In particular, the resonant excitation of the C1s(CH2) to the LUMO leads to a large intensity increase in the region of the first satellite state, whereas no dramatic changes are observed for the C1s(CCl2) excitation. [ABSTRACT FROM AUTHOR]

It is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of small nuclear ribonucleoproteins (snRNPs): essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intranuclear snRNP mobility, we employed a panel of inhibitors of different stages of pre-mRNA processing. This in vivo modelling demonstrates that snRNP mobility is altered directly as a result of impaired snRNP maturation. Current models of nuclear dynamics predict that subnuclear structures, including the spliceosome, form by self-organization mediated by stochastic interactions between their molecular components. Thus, alteration of the intranuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA. [ABSTRACT FROM AUTHOR]

Linker histone H1 is a fundamental chromosomal protein involved in the maintenance of higher-ordered chromatin organization. The exchange dynamics of histone H1 correlates well with chromatin plasticity. A variety of core histone chaperones involved in core histone dynamics has been identified, but the identity of the linker histone chaperone in the somatic cell nucleus has been a longstanding unanswered question. Here we show that Template Activating Factor-I (TAF-I, also known as protein SET) is involved in histone H1 dynamics as a linker histone chaperone. Among previously identified core histone chaperones and linker histone chaperone candidates, only TAF-I was found to be associated specifically with histone H1 in mammalian somatic cell nuclei. TAF-I showed linker histone chaperone activity in vitro. Fluorescence recovery after photobleaching analyses revealed that TAF-I is involved in the regulation of histone H1 dynamics in the nucleus. Therefore, we propose that TAF-I is a key molecule that regulates linker histone-mediated chromatin assembly and disassembly. [ABSTRACT FROM AUTHOR]

Abstract: Modern nucleon-nucleon interaction models can be probed quantitatively in the three-nucleon (3N) environment by comparing predictions based on rigorous solutions of the Faddeev equations with the measured observables. Proper description of the experimental data can be achieved only if the models are supplemented with additional dynamical ingredients: subtle traces of suppressed degrees of freedom, e_ectively introduced by means of genuine three-nucleon forces and e_ects of the Coulomb force. As an example of precision studies of 3N system dynamics, new generation measurements of the 1H(∼d,pp)n breakup reaction at 130 MeV are considered. Large sets of high accuracy, exclusive cross-section and analyzing power data acquired in these projects contribute significantly to constrain the physical assumptions underlying the theoretical interaction models. Comparisons of the cross-section data with the predictions using nuclear interactions generated in various ways, allowed to establish importance of including both, the 3N and the Coulomb forces to strongly improve description of the whole data set. Discrepancies observed in reproducing the analyzing power data hint at still persisting incompleteness of modeling the 3N system interaction dynamics. [Copyright &y& Elsevier]