Centripetal nuclear shape fluctuations associate with chromatin condensation towards mitosis

The cell nucleus plays a central role in several key cellular processes, including chromosome organisation, replication and transcription. Recent work intriguingly suggests an association between nuclear mechanics and cell-cycle progression, but many aspects of this connection remain unexplored. Here, by monitoring nuclear shape fluctuations at different cell cycle stages, we uncover increasing inward fluctuations in late G2 and early mitosis, which are initially transient, but develop into instabilities that culminate into nuclear-envelope breakdown in mitosis. Perturbation experiments and correlation analysis reveal an association of these processes with chromatin condensation. We propose that the contrasting forces between an extensile stress and centripetal pulling from chromatin condensation could link mechanically chromosome condensation and nuclear-envelope breakdown, the two main nuclear processes during mitosis.

Revealing RCOR2 as a regulatory component of nuclear speckles

Background Nuclear processes such as transcription and RNA maturation can be impacted by subnuclear compartmentalization in condensates and nuclear bodies. Here, we characterize the nature of nuclear granules formed by REST corepressor 2 (RCOR2), a nuclear protein essential for pluripotency maintenance and central nervous system development. Results Using biochemical approaches and high-resolution microscopy, we reveal that RCOR2 is localized in nuclear speckles across multiple cell types, including neurons in the brain. RCOR2 forms complexes with nuclear speckle components such as SON, SRSF7, and SRRM2. When cells are exposed to chemical stress, RCOR2 behaves as a core component of the nuclear speckle and is stabilized by RNA. In turn, nuclear speckle morphology appears to depend on RCOR2. Specifically, RCOR2 knockdown results larger nuclear speckles, whereas overexpressing RCOR2 leads to smaller and rounder nuclear speckles. Conclusion Our study suggests that RCOR2 is a regulatory component of the nuclear speckle bodies, setting this co-repressor protein as a factor that controls nuclear speckles behavior.

Pluripotency transcription factors at the focus: the phase separation paradigm in stem cells

The transcription factors (TFs) OCT4, SOX2 and NANOG are key players of the gene regulatory network of pluripotent stem cells. Evidence accumulated in recent years shows that even small imbalances in the expression levels or relative concentrations of these TFs affect both, the maintenance of pluripotency and cell fate decisions. In addition, many components of the transcriptional machinery including RNA polymerases, cofactors and TFs such as those required for pluripotency, do not distribute homogeneously in the nucleus but concentrate in multiple foci influencing the delivery of these molecules to their DNA-targets. How cells control strict levels of available pluripotency TFs in this heterogeneous space and the biological role of these foci remain elusive. In recent years, a wealth of evidence led to propose that many of the nuclear compartments are formed through a liquid–liquid phase separation process. This new paradigm early penetrated the stem cells field since many key players of the pluripotency circuitry seem to phase-separate. Overall, the formation of liquid compartments may modulate the kinetics of biochemical reactions and consequently regulate many nuclear processes. Here, we review the state-of-the-art knowledge of compartmentalization in the cell nucleus and the relevance of this process for transcriptional regulation, particularly in pluripotent stem cells. We also highlight the recent advances and new ideas in the field showing how compartmentalization may affect pluripotency preservation and cell fate decisions.

Revealing RCOR2 as a regulatory component of nuclear speckles

Background Nuclear processes such as transcription and RNA maturation can be impacted by subnuclear compartmentalization in condensates and nuclear bodies. Here we characterize the nature of nuclear granules formed by REST corepressor 2 (RCOR2), a nuclear protein essential for pluripotency maintenance and central nervous system development. Results Using biochemical approaches and high-resolution microscopy, we reveal that RCOR2 is localized in nuclear speckles across multiple cell types, including neurons in the brain. RCOR2 forms complexes with nuclear speckle components such as SON, SRSF7, and SRRM2. When cells are exposed to chemical stress, RCOR2 behaves as a core component of the nuclear speckle and is stabilized by RNA. In turn, nuclear speckle morphology appears to depend on RCOR2. Specifically, RCOR2 knockdown results larger nuclear speckles, whereas overexpressing RCOR2 leads to smaller and rounder nuclear speckles. Conclusion Our study suggests that RCOR2 is a regulatory component of the nuclear speckle bodies, setting this co-repressor protein as a factor that controls nuclear speckles behavior.

Precise measurements of chromatin diffusion dynamics by modeling using Gaussian processes

The spatiotemporal organization of chromatin influences many nuclear processes: from chromosome segregation to transcriptional regulation. To get a deeper understanding of these processes, it is essential to go beyond static viewpoints of chromosome structures, to accurately characterize chromatin’s diffusion properties. We present GP-FBM: a computational framework based on Gaussian processes and fractional Brownian motion to extract diffusion properties from stochastic trajectories of labeled chromatin loci. GP-FBM uses higher-order temporal correlations present in the data, therefore, outperforming existing methods. Furthermore, GP-FBM allows to interpolate incomplete trajectories and account for substrate movement when two or more particles are present. Using our method, we show that average chromatin diffusion properties are surprisingly similar in interphase and mitosis in mouse embryonic stem cells. We observe surprising heterogeneity in local chromatin dynamics, correlating with potential regulatory activity. We also present GP-Tool, a user-friendly graphical interface to facilitate usage of GP-FBM by the research community.

Public Acceptance of ITER-Tokamak Fusion Power

One of the U.S. Electric Power Research Institute’s criteria for practical fusion power is public acceptance. In this analysis we consider the potential public acceptance of ITER-tokamak fusion power. Because ITER-like reactors are not likely to be commercially ready before mid-century, a forecast of public acceptance is very difficult. We break “the public” down into four entities: 1) Rank and file consumers, 2) Governments [local, state, & federal including regulators], 3) NGOs including environmental groups, and 4) Electric utilities. We assert that ITER-tokamaks will be evaluated in the context of fission power because both are nuclear processes. We observe that ITER-tokamak fusion will present radioactive hazards and be extremely expensive. Three possible futures for fission nuclear mid-century are: 1) full acceptance, 2) middling acceptance, and 3) rejection. If fission power is accepted mid-century, then ITER-tokamak fusion stands the best chance of being publicly acceptable, its largest drawback being very high cost. If fission power is of middling acceptance, then ITER-tokamak fusion might be marginally more acceptable because of its much shorter life radioactive waste. If fission power is unacceptable, then ITER-tokamak fusion acceptance will be very difficult.

Nuclear Processes in Dark Interstellar Matter of H(0) Decrease the Hope of Migrating to Exoplanets

It is still generally assumed that interstellar travel will be possible after purely technical development and thus that mankind can move to some suitable exoplanet when needed. However, recent research indicates this not to be the case, since interstellar space is filled with enough ultradense hydrogen H(0) as stable condensed dark matter (Holmlid, Astrophysical Journal 2018) to make interstellar space travel at the required and technically feasible relativistic velocities (Holmlid et al, Acta Astronautica 2020) almost impossible. H(0) can be observed to exist in space from the so-called extended red emission (ERE) features observed in space. A recent review (Holmlid et al., Physica Scripta 2019) describes the properties of H(0). H(0) gives nuclear processes emitting kaons and other particles, with kinetic energies even above 100 MeV after induction for example by fast particle (spaceship) impact. These high particle energies give radiative temperatures of 12000 K in collisions against a solid surface and will rapidly destroy any spaceship structure moving into the H(0) clouds at relativistic velocity. The importance of preserving our ecosystem is pointed out, since travel to suitable exoplanets may be impossible. The possibilities of instead clearing interstellar space from H(0) are discussed, eventually providing tunnels suitable for relativistic interstellar transport. Finding regions with low intensity of ERE could even be a way to identify space-cleaning activities and thus to locate earlier space-travelling civilizations.

Predicting Chromosome Flexibility from the Genomic Sequence Based on Deep Learning Neural Networks

Background: The open and accessible regions of the chromosome are more likely to be bound by transcription factors which are important for nuclear processes and biological functions. Studying the change of chromosome flexibility can help to discover and analyze disease markers and improve the efficiency of clinical diagnosis. Current methods for predicting chromosome flexibility based on Hi-C data include the flexibility-rigidity index (FRI) and the Gaussian network model (GNM), which have been proposed to characterize chromosome flexibility. However, these methods require the chromosome structure data based on 3D biological experiments, which is time-consuming and expensive. Objective: Generally, the folding and curling of the double helix sequence of DNA have a great impact on chromosome flexibility and function. Motivated by the success of genomic sequence analysis in biomolecular function analysis, we hope to propose a method to predict chromosome flexibility only based on genomic sequence data. Method: We propose a new method (named "DeepCFP") using deep learning models to predict chromosome flexibility based on only genomic sequence features. The model has been tested in the GM12878 cell line. Results: The maximum accuracy of our model has reached 91%. The performance of DeepCFP is close to FRI and GNM. Conclusion: The DeepCFP can achieve high performance only based on genomic sequence.

Meson bunches formed by pulsed laser-induced processes in ultra-dense hydrogen H(0)

Ultra-dense hydrogen H(0) (reviewed in Holmlid and Zeiner-Gundersen, Physica Scripta 2019 ) consists of small strongly bound molecules with interatomic distance of 0.56 pm in spin state s = 1. It is a useful nuclear fuel for energy generation, giving heat above break-even (Holmlid, AIP Advances 2015) in laser-induced processes (Holmlid, Int. J. Hydr. Energy 2021). Nuclear processes in H(0) emit particles in typical meson decay chains with kinetic energy up to 100 MeV. These mesons decay and generate fast muons at up to 500 MeV energy at current densities of several mA cm-2 at 1–2 m distances, which corresponds to 1013 -1014 muons formed per laser pulse. It is shown that the mesons decay in chain processes with well-defined meson time constants in the range 10–60 ns. The time varying signals from H(0) agree well with mesons M in decay chains as A ◊ M ◊ N where N is a signal muon. M may be a charged kaon K± (decay time constant at rest 12.4 ns) or a charged pion π± (decay time constant at rest 26 ns) or a long-lived neutral kaon \({\text{K}}_{L}^{0}\) (decay time constant at rest 51 ns). Ultra-dense protium p(0) gives the same time constants as D(0) but slightly different decay-chains. The meson bunches observed are similar to the meson bunches from nucleon + antinucleon annihilation. The energy gain in the nuclear process is at least 8000, strongly indicating baryon annihilation for which process further evidence is given in other recent publications.

Gradual evolution of allopolyploidy in Arabidopsis suecica

Most diploid organisms have polyploid ancestors. The evolutionary process of polyploidization is poorly understood but has frequently been conjectured to involve some form of ‘genome shock’, such as genome reorganization and subgenome expression dominance. Here we study polyploidization in Arabidopsis suecica, a post-glacial allopolyploid species formed via hybridization of Arabidopsis thaliana and Arabidopsis arenosa. We generated a chromosome-level genome assembly of A. suecica and complemented it with polymorphism and transcriptome data from all species. Despite a divergence around 6 million years ago (Ma) between the ancestral species and differences in their genome composition, we see no evidence of a genome shock: the A. suecica genome is colinear with the ancestral genomes; there is no subgenome dominance in expression; and transposon dynamics appear stable. However, we find changes suggesting gradual adaptation to polyploidy. In particular, the A. thaliana subgenome shows upregulation of meiosis-related genes, possibly to prevent aneuploidy and undesirable homeologous exchanges that are observed in synthetic A. suecica, and the A. arenosa subgenome shows upregulation of cyto-nuclear processes, possibly in response to the new cytoplasmic environment of A. suecica, with plastids maternally inherited from A. thaliana. These changes are not seen in synthetic hybrids, and thus are likely to represent subsequent evolution.