Nuclear Dynamics Research Articles

A Yeast Mitotic Tale for the Nucleus and the Vacuoles to Embrace.

The morphology of the nucleus is roughly spherical in most eukaryotic cells. However, this organelle shape needs to change as the cell travels through narrow intercellular spaces during cell migration and during cell division in organisms that undergo closed mitosis, i.e., without dismantling the nuclear envelope, such as yeast. In addition, the nuclear morphology is often modified under stress and in pathological conditions, being a hallmark of cancer and senescent cells. Thus, understanding nuclear morphological dynamics is of uttermost importance, as pathways and proteins involved in nuclear shaping can be targeted in anticancer, antiaging, and antifungal therapies. Here, we review how and why the nuclear shape changes during mitotic blocks in yeast, introducing novel data that associate these changes with both the nucleolus and the vacuole. Altogether, these findings suggest a close relationship between the nucleolar domain of the nucleus and the autophagic organelle, which we also discuss here. Encouragingly, recent evidence in tumor cell lines has linked aberrant nuclear morphology to defects in lysosomal function.

Insights into solvent effect on selective production of furfural and 5-hydroxymethylfurfural from fructose

Selective transformation of biomass-based feedstocks into value-added energy chemical is one of the most critical steps in biorefinery process. Herein, we gave insight into solvent effect on selective production of furfural or 5-hydroxymethylfurfural (HMF) from fructose with the combination of experiments, nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulation. It was found that the selective formation of furfural and HMF was mainly dominated by solvent polarity and basicity, and solvent properties could change the reaction pathway of fructose. High polarity-high basicity solvent promoted HMF formation, while high polarity-low basicity solvent was conductive to furfural formation. The preferential arrangement of solvents around fructose tautomers, especially on different C-OH, consequently led to the different products. High yields of furfural (76.2%) and HMF (90.5%) were obtained in the solvents of γ-butyrolactone (GBL)–H2O and dimethyl sulfoxide (DMSO)–H2O.

General exponential basis set parametrization: Application to time-dependent bivariational wave functions.

We present equations of motion (EOMs) for general time-dependent wave functions with exponentially parameterized biorthogonal basis sets. The equations are fully bivariational in the sense of the time-dependent bivariational principle and offer an alternative, constraint-free formulation of adaptive basis sets for bivariational wave functions. We simplify the highly non-linear basis set equations using Lie algebraic techniques and show that the computationally intensive parts of the theory are, in fact, identical to those that arise with linearly parameterized basis sets. Thus, our approach offers easy implementation on top of existing code in the context of both nuclear dynamics and time-dependent electronic structure. Computationally tractable working equations are provided for single and double exponential parametrizations of the basis set evolution. The EOMs are generally applicable for any value of the basis set parameters, unlike the approach of transforming the parameters to zero at each evaluation of the EOMs. We show that the basis set equations contain a well-defined set of singularities, which are identified and removed by a simple scheme. The exponential basis set equations are implemented in conjunction with the time-dependent modals vibrational coupled cluster (TDMVCC) method, and we investigate the propagation properties in terms of the average integrator step size. For the systems we test, the exponentially parameterized basis sets yield slightly larger step sizes compared to the linearly parameterized basis set.

Young and Senescent Cells: Distinct Nuclear F-actin Patterns Upon Latrunculin B Induction

Both cellular senescence and cytoskeleton are involved in the formation of many diseases and cell signaling pathways. Although recent studies have shown that F-actin is involved in DNA damage repair, chromatin decompression, gene transcription regulation, and cell fate determination. But studies on F-actin and aging are still absence. It is unclear whether nuclear F-actin is present during cellular senescence. Here, by confocal optical sectioning and time-lapse imaging, we found acitn chrommobody-TagGFP2-NLS shows the beneficial on investigating senescent human fibroblast IMR-90 cells. To induce the nuclear F-actin assembly in single cell, we uesd Latrunculin B (latB) which a cytoplasmic F-actin polymerization inhibitor. It is currently unknown whether the nuclear F-actin cytoskeleton in young and senescent cells responds differently to latB treatment. Here, latB application induces distinct nuclear F-actin patterns and dynamics in young and senescent cells. Thus, after analyzing the results of actin dynamic we demonstrate a diverse effect of latB on the nuclear F-actin cytoskeleton in young and senescent cells.

Weak Neutrino (Antineutrino) Charged-Current Responses and Scaling for Nuclear Matter in the Relativistic Mean Field

A systematic analysis of the weak responses for charged-current quasielastic neutrino-nucleus reactions is presented within the scheme of a fully relativistic microscopic model considering momentum-dependent scalar and vector mean field potentials in both the initial and final nucleon states. The responses obtained are compared with the ones corresponding to simpler approaches: energy-independent potentials and the relativistic plane wave limit in the final state, i.e., no potentials applied to the outgoing particle. The analysis is also extended to the scaling phenomenon, which provides additional information regarding nuclear dynamics. Results for the scaling function are shown for various nuclei and different values of the transferred momentum in order to analyze the behavior of the relativistic scalar and vector mean field potentials.

Enhanced transverse nuclear magnetization of an atomic co-magnetometer at the optimal oscillating magnetic field

The nuclear magnetization produced by hyperpolarized noble-gas molecules of co-magnetometers presents excellent potential in ultrahigh accuracy measurement. Here we demonstrate an optimization method of the oscillating magnetic field to enhance the transverse nuclear magnetization for atomic co-magnetometers operated in the nuclear magnetic resonance (NMR) regime. Under normal operating conditions, the absolute magnetic field produced by transverse nuclear magnetization is studied based on the nuclear spin dynamics and measured by the in-situ magnetometer experimentally. The different oscillating magnetic fields are applied to obtain the maximum transverse nuclear magnetization in various operating temperatures. Combined with the measurements, we reveal the relationship between the transverse nuclear magnetization and the relaxation time, which is consistent with our method. The optimization method makes selecting the optimal operating point for each atomic co-magnetometer quick and accurate to enhance transverse nuclear magnetization. In addition, operating at the optimal oscillating magnetic field can effectively reduce the bias instability of the atomic co-magnetometer.

Nuclear envelope dynamics in connection to chromatin remodeling.

The nucleus is a central organelle of eukaryotic cells undergoing dynamic structural changes during cellular fundamental processes such as proliferation and differentiation. These changes rely on the integration of developmental and stress signals at the nuclear envelope (NE), orchestrating responses at the nucleo-cytoplasmic interface for efficient genomic functions such as DNA transcription, replication and repair. While in animals, correlation has already been established between NE dynamics and chromatin remodeling using last-generation tools and cutting-edge technologies, this topic is just emerging in plants, especially in response to mechanical cues. This review summarizes recent data obtained in this field with more emphasis on the mechanical stress response. It also highlights similarities/differences between animal and plant cells at multiples scales, from the structural organization of the nucleo-cytoplasmic continuum to the functional impacts of NE dynamics.

A theoretical study of the time-resolved x-ray absorption spectrum of the photoionized BT-1T cation.

The time-resolved x-ray absorption spectrum of the BT-1T cation (BT-1T+) is theoretically simulated in order to investigate the charge transfer reaction of the system. We employ both trajectory surface hopping and quantum dynamics to simulate the structural evolution over time and the changes in the state populations. To compute the static x-ray absorption spectra (XAS) of the ground and excited states, we apply both the time-dependent density functional theory and the coupled cluster singles and doubles method. The results obtained are in good agreement between the methods. It is, furthermore, found that the small structural changes that occur during the reaction have little effect on the static XAS. Hence, the tr-XAS can be computed based on the state populations determined from a nuclear dynamics simulation and one set of static XAS calculations, utilizing the ground state optimized geometry. This approach can save considerable computational resources, as the static spectra need not to be calculated for all geometries. As BT-1T is a relatively rigid molecule, the outlined approach should only be considered when investigating non-radiative decay processes in the vicinity of the Franck-Condon point.

13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase.

Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures.

Comparing semiclassical mean-field and 1-exciton approximations in evaluating optical response under strong light-matter coupling conditions.

The rigorous quantum mechanical description of the collective interaction of many molecules with the radiation field is usually considered numerically intractable, and approximation schemes must be employed. Standard spectroscopy usually contains some levels of perturbation theory, but under strong coupling conditions, other approximations are used. A common approximation is the 1-exciton model in which processes involving weak excitations are described using a basis comprising the ground state and singly excited states of the molecule cavity-mode system. In another frequently used approximation in numerical investigations, the electromagnetic field is described classically, and the quantum molecular subsystem is treated in the mean-field Hartree approximation with its wavefunction assumed to be a product of single molecules' wavefunctions. The former disregards states that take long time to populate and is, therefore, essentially a short time approximation. The latter is not limited in this way, but by its nature, disregards some intermolecular and molecule-field correlations. In this work, we directly compare results obtained from these approximations when applied to several prototype problems involving the optical response of molecules-in-optical cavities systems. In particular, we show that our recent model investigation [J. Chem. Phys. 157, 114108 (2022)] of the interplay between the electronic strong coupling and molecular nuclear dynamics using the truncated 1-exciton approximation agrees very well with the semiclassical mean-field calculation.

Macroevolutionary patterns in intragenomic rDNA variability among planktonic foraminifera.

Ribosomal intragenomic variability in prokaryotes and eukaryotes is a genomic feature commonly studied for its inflationary impact on molecular diversity assessments. However, the evolutionary mechanisms and distribution of this phenomenon within a microbial group are rarely explored. Here, we investigate the intragenomic variability in 33 species of planktonic foraminifera, calcifying marine protists, by inspecting 2,403 partial SSU sequences obtained from single-cell clone libraries. Our analyses show that polymorphisms are common among planktonic foraminifera species, but the number of polymorphic sites significantly differs among clades. With our molecular simulations, we could assess that most of these mutations are located in paired regions that do not affect the secondary structure of the SSU fragment. Finally, by mapping the number of polymorphic sites on the phylogeny of the clades, we were able to discuss the evolution and potential sources of intragenomic variability in planktonic foraminifera, linking this trait to the distinctive nuclear and genomic dynamics of this microbial group.

Label-Free Cytometric Evaluation of Mitosis via Stimulated Raman Scattering Microscopy and Spectral Phasor Analysis.

Hyperspectral stimulated Raman scattering (SRS) microscopy is a robust imaging tool for the analysis of biological systems. Here, we present a unique perspective, a label-free spatiotemporal map of mitosis, by integrating hyperspectral SRS microscopy with advanced chemometrics to assess the intrinsic biomolecular properties of an essential process of mammalian life. The application of spectral phasor analysis to multiwavelength SRS images in the high-wavenumber (HWN) region of the Raman spectrum enabled the segmentation of subcellular organelles based on innate SRS spectra. Traditional imaging of DNA is primarily reliant on using fluorescent probes or stains which can affect the biophysical properties of the cell. Here, we demonstrate the label-free visualization of nuclear dynamics during mitosis coupled with an evaluation of its spectral profile in a rapid and reproducible manner. These results provide a snapshot of the cell division cycle and chemical variability between intracellular compartments in single-cell models, which is central to understanding the molecular foundations of these fundamental biological processes. The evaluation of HWN images by phasor analysis also facilitated the differentiation between cells in separate phases of the cell cycle based solely on their nuclear SRS spectral signal, which offers an interesting label-free approach in combination with flow cytometry. Therefore, this study demonstrates that SRS microscopy combined with spectral phasor analysis is a valuable method for detailed optical fingerprinting at the subcellular level.

Investigating the function and design of molecular materials through terahertz vibrational spectroscopy.

Terahertz spectroscopy has proved to be an essential tool for the study of condensed phase materials. Terahertz spectroscopy probes the low-frequency vibrational dynamics of atoms and molecules, usually in the condensed phase. These nuclear dynamics, which typically involve displacements of entire molecules, have been linked to bulk phenomena ranging from phase transformations to semiconducting efficiency. The terahertz region of the electromagnetic spectrum has historically been referred to as the 'terahertz gap', but this is a misnomer, as there exist a multitude of methods for accessing terahertz frequencies, and now there are cost-effective instruments that have made terahertz studies much more user-friendly. This Review highlights some of the most exciting applications of terahertz vibrational spectroscopy so far, and provides an in-depth overview of the methods of this technique and its utility to the study of the chemical sciences.

Transcription factor localization dynamics and DNA binding drive distinct promoter interpretations

Environmental information may be encoded in the temporal dynamics of transcription factor (TF) activation and subsequently decoded by gene promoters to enact stimulus-specific gene expression programs. Previous studies of this behavior focused on the encoding and decoding of information in TF nuclear localization dynamics, yet cells control the activity of TFs in myriad ways, including by regulating their ability to bind DNA. Here, we use light-controlled mutants of the yeast TF Msn2 as a model system to investigate how promoter decoding of TF localization dynamics is affected by changes in the ability of the TF to bind DNA. We find that yeast promoters directly decode the light-controlled localization dynamics of Msn2 and that the effects of changing Msn2 affinity on that decoding behavior are highly promoter dependent, illustrating how cells could regulate TF localization dynamics and DNA binding in concert for improved control of gene expression.

Including vibrational effects in magnetic circular dichroism spectrum calculations in the framework of excited state dynamics.

In this work, we present a computational approach that is able to incorporate vibrational effects in the computations of magnetic circular dichroism (MCD) spectra. The method combines our previous implementations to model absorption as well as fluorescence and phosphorescence spectra in the framework of excited state dynamics with a new technique to calculate MCD intensities, where molecular orientational averages are treated via semi-numerical quadrature. The implementation relies on a path integral approach that is employed to compute nuclear dynamics under the harmonic oscillator approximation (accounting for the nuclear potential energy surface) together with quasi-degenerate perturbative theory (to include the perturbation of an external magnetic field). We evaluate our implementation with a selected molecular set consisting of five aromatic organic molecules, namely, 1,4-benzoquinone, naphthalene, 2-naphthylamine, 2-naphthaldehyde, and benzene; we also included the MnO4- and the [Co(NH3)6]3+ transition metal complexes. This set is used to validate the ability of the approach to compute MCD A- and B-terms in conjunction with time-dependent density functional theory. The computed intensities are discussed in terms of the overall quality of the electronic structure treatments, vibrational modes, and the quality of the nuclear Hessians. It is shown that in the cases in which the potential energy surface is accurately represented, electric dipole-forbidden transitions are vibrationally activated, producing intensities relative to the dipole-allowed transitions in the same order of magnitude as the experimental measurements.

Dynamical Simulations of Carotenoid Photoexcited States Using Density Matrix Renormalization Group Techniques.

We present a dynamical simulation scheme to model the highly correlated excited state dynamics of linear polyenes. We apply it to investigate the internal conversion processes of carotenoids following their photoexcitation. We use the extended Hubbard-Peierls model, , to describe the π-electronic system coupled to nuclear degrees of freedom. This is supplemented by a Hamiltonian, , that explicitly breaks both the particle-hole and two-fold rotation symmetries of idealized carotenoid structures. The electronic degrees of freedom are treated quantum mechanically by solving the time-dependent Schrödinger equation using the adaptive time-dependent DMRG (tDMRG) method, while nuclear dynamics are treated via the Ehrenfest equations of motion. By defining adiabatic excited states as the eigenstates of the full Hamiltonian, , and diabatic excited states as eigenstates of , we present a computational framework to monitor the internal conversion process from the initial photoexcited 11Bu+ state to the singlet triplet-pair states of carotenoids. We further incorporate Lanczos-DMRG to the tDMRG-Ehrenfest method to calculate transient absorption spectra from the evolving photoexcited state. We describe in detail the accuracy and convergence criteria for DMRG, and show that this method accurately describes the dynamical processes of carotenoid excited states. We also discuss the effect of the symmetry-breaking term, , on the internal conversion process, and show that its effect on the extent of internal conversion can be described by a Landau-Zener-type transition. This methodological paper is a companion to our more explanatory discussion of carotenoid excited state dynamics in Manawadu, D.; Georges, T. N.; Barford, W. Photoexcited State Dynamics and Singlet Fission in Carotenoids. J. Phys. Chem. A 2023, 127, 1342.

Real-Space and Real-Time Propagation for Correlated Electron-Nuclear Dynamics Based on Exact Factorization.

We present coupled equations of motion for correlated electron-nuclear dynamics for real-space and real-time propagation with a proper electron-nuclear correlation (ENC) from the exact factorization. Since the original ENC term from the exact factorization is non-Hermitian, the numerical instability arises as we propagate an electronic wave function. In this paper, we propose a Hermitian-type ENC term which depends on the electron density matrix and the nuclear quantum momentum. Moreover, we show that the Hermitian property of the electron-nuclear correlation term can capture quantum (de)coherence with a stable numerical real-space and real-time propagation. As an application, we demonstrate a real-space and real-time propagation of an electronic wave function coupled to trajectory-based nuclear motion for a one-dimensional model Hamiltonian. Our approach can capture nonadiabatic phenomena as well as quantum decoherence in excited state molecular dynamics. In addition, we propose a scheme to extend the current approach to many-body electronic states based on real-time time-dependent density functional theory, testing the nonadiabatic dynamics of a simple molecular system.

Assessing the theory-data tension in neutrino-induced charged pion production: The effect of final-state nucleon distortion

Pion production on nuclei constitutes a significant part of the total cross section in experiments involving few-GeV neutrinos. Combined analyses of data on deuterium and heavier nuclei points to tensions between the bubble-chamber data and the data of the $\mathrm{MINER}\ensuremath{\nu}\mathrm{A}$ experiment, which are often ascribed to unspecified nuclear effects. In experimental analysis use is made of approximate treatments of nuclear dynamics, usually in a Fermi gas approach with classical treatments of the reaction mechanism, and fits are often performed by simply rescaling cross sections. To understand the origin of these tensions, check the validity of approximations, and to further advance the description of neutrino pion production on nuclei, a microscopic quantum mechanical framework is needed to compute nuclear matrix elements. We use the local approximation to the relativistic distorted wave impulse approximation to calculate the nuclear matrix elements. We include the distortion of wave functions of the final-state nucleon in a real energy-dependent potential. We compare results with and without distortion. To perform this comparison under conditions relevant to neutrino experiments, we compute cross sections for the $\mathrm{MINER}\ensuremath{\nu}\mathrm{A}$ and T2K charged-pion production datasets. The inclusion of nucleon distortion leads to a reduction of the cross section up to 10%, but to no significant change in shape of the flux-averaged cross sections. Results with and without distortion compare favorably to experimental data, with the exception of the low-${Q}^{2}$ $\mathrm{MINER}\ensuremath{\nu}\mathrm{A}$ ${\ensuremath{\pi}}^{+}$ data. We point out that hydrogen target data from BEBC is also overpredicted at low ${Q}^{2}$, and the data-model discrepancy is similar in shape and magnitude as what is found in comparison to $\mathrm{MINER}\ensuremath{\nu}\mathrm{A}$ data. Including nucleon distortion alone cannot explain the overprediction of low-${Q}^{2}$ cross sections measured by $\mathrm{MINER}\ensuremath{\nu}\mathrm{A}$. The similar overprediction of BEBC data on hydrogen means that it is impossible to ascribe this discrepancy solely to a nuclear effect. Axial form factors might not be constrained in a satisfactory way by the Argonne and Brookhaven National Laboratories (ANL/BNL) data alone. Axial couplings and their ${Q}^{2}$ dependence should ideally be derived from more precise data on hydrogen and deuterium. Nuclear matrix elements should be tested with e.g., electron scattering data for which nucleon level physics is better constrained.

Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases

Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Streptococcus pyogenes serotypes secrete two multi-modular endo-β-N-acetylglucosaminidases, EndoS and EndoS2, that specifically deglycosylate the conserved N-glycan at Asn297 on IgG Fc, disabling antibody-mediated effector functions. Amongst thousands of known carbohydrate-active enzymes, EndoS and EndoS2 represent just a handful of enzymes that are specific to the protein portion of the glycoprotein substrate, not just the glycan component. Here, we present the cryoEM structure of EndoS in complex with the IgG1 Fc fragment. In combination with small-angle X-ray scattering, alanine scanning mutagenesis, hydrolytic activity measurements, enzyme kinetics, nuclear magnetic resonance and molecular dynamics analyses, we establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by EndoS and EndoS2. Our results provide a rational basis from which to engineer novel enzymes with antibody and glycan selectivity for clinical and biotechnological applications.

Ultrafast laser induced charge migration with de- and re-coherences in polyatomic molecules: A general method with application to pyrene.

We develop a general method to study ultrafast laser induced charge migration in molecules, which includes both electronic and nuclear dynamics. The method can be applied to relatively large systems. A detailed analysis of charge migration in pyrene is performed. Decoherences and recoherences of charge migration in pyrene are found and explained in terms of nuclear motions.