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Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.

A targeted nano-drug delivery system has provided great potential and benefits to the diagnosis and therapy of cancers. Cell entry is a critical step for taking effect of the targeted nano-drug. In this report, the dynamics of delivering a single aptamer targeted polyamindoamine-camptothecin-AS1411 (PAMAM-CPT-AS1411) nano-drug into cells was investigated using a force tracing technique based on atomic force microscopy. The results show that the specific interaction of AS1411 and nucleolin, which is overexpressed on cancer cells, enhances the efficiency of the PAMAM-CPT-AS1411 cell entry. Moreover, the specific interaction induced receptor-mediated endocytosis prolongs the duration and decreases the speed of a single PAMAM-CPT-AS1411 cell entry, which is helpful to understand the targeted nano-drugs prolonging the therapeutic drug level. However, the required force for PAMAM-CPT-AS1411 cell entry is not changed. This report will provide a novel and potential method for achieving the precise dynamics of targeted nano-drug delivery.

Radial [4]catenane isomers in which the dynamics of the interlocked macrocycles are encoded by the covalent structure of the central macrocyclic backbone are described. Shuttling motion of the interlocked β-cyclodextrin was found to be dependent on both the position and interaction strength of the interlocked cucurbit[6]urils on the central macrocycle. This work demonstrates that the dynamics of different mechanically bonded macrocycles in a hetero[n]catenane can be coordinated complementarily, suggesting the possible exploitation of higher-order [n]catenanes as the next level molecular machines in which more complex tasks can be performed with sophisticated intramolecular motions.

Dynamics are intricately linked with activity and selectivity when it comes to catalysis, as noted for instance in the enzymatic principles of induced fit and allostery, and yet the range of motions heterogeneous catalytic sites are able to undergo is poorly understood. Solid-state nuclear magnetic resonance (NMR) spectroscopy is perhaps the only tool capable of probing the rapid conformational dynamics found in heterogeneous catalysts but has historically been restricted by its low sensitivity, limiting the detail with which structures can be resolved. Here, we apply solid-state NMR and dynamic nuclear polarization, in combination with density functional theory modeling, to reveal the high-resolution structure and motional freedom of a scandium supported complex in three dimensions. The results are contrasted with the study of the analogous homoleptic complex in the crystalline state, highlighting the impacts that surface structure may have on the dynamics of supported complexes.

To the best of our knowledge, this is the first molecular dynamics simulation study on the dimeric form of the LuxS enzyme from Vibrio cholerae to evaluate its structural and dynamical properties including the dynamics of the interface formed by the two monomeric chains of the enzyme. The dynamics of the interfacial region were investigated in terms of inter-residual contacts and the associated interface area of the enzyme in its ligand-free and ligand–bound states which produced characteristics contrast in the interfacial dynamics. Moreover, the binding patterns of the two inhibitors (RHC and KRI) to the enzyme forming two different enzyme–ligand complexes were analyzed which pointed towards a varying inhibition potential of the inhibitors as also revealed by the free energies of ligand binding. It is shown that KRI is a more potent inhibitor than RHC – a substrate analogue, showing correlation with experimental data. Moreover, the role of a loop in chain B of the enzyme was found to facilitate the binding of RHC similar to that of the substrate, while KRI demonstrates a differing binding pattern. The computation of the free energy of binding for the two ligands was also carried out via thermodynamic integration which ultimately served to correlate the dynamical properties with the inhibition potential of two different ligands against the enzyme. Furthermore, this successful study provides a rational to suggest novel LuxS inhibitors which could become promising candidates to treat the diseases caused by a broad variety of bacterial species.

The dynamics and stability of premixed hydrogen-air flames in square microchannels with heated walls were investigated through three-dimensional direct numerical simulations. The inlet velocity and equivalence ratio were 1.5 m/s and 0.5. The effect of the wall temperature gradient characteristics on the flame dynamics and stability was examined varying the width and location of the wall temperature gradient for a channel height of 1.5 mm. Five distinct flame modes were observed at different wall temperature profiles: flame with repetitive extinction-ignition (FREI), pulsating flame, laterally oscillating flame, spinning flame, and steady flame modes. Furthermore, transitions between these flame modes were observed for specific inflow and boundary conditions. The effect of the channel height on the flame stability was investigated by varying the channel height from 1.0 mm to 1.677 mm for a fixed wall temperature gradient. As the channel height was increased, four of the flame modes, namely, FREI, laterally oscillating flame, spinning flame, and steady flame modes appeared sequentially. To determine whether this sequential appearance was associated with the variation of the wall heat loss, the maximum wall temperature was changed by small amounts. For a lower wall temperature, the laterally oscillating flame mode transitioned to the FREI mode, and for a higher wall temperature, unstable flame modes such as the FREI and laterally oscillating flame modes disappeared, resulting in stable flame.

The glass transition and dynamics of densely grafted semiflexible polymer brushes are studied by molecular dynamics simulation. The glass transition temperature (Tg) increases with the polymer rigidity. The local glass transition temperature (Tg,local) is estimated from the temperature-dependent dynamics of individual segments including the lateral position fluctuation and lateral mean square displacement. Different from the flexible polymer brush, Tg,local of semiflexible polymer brushes is roughly independent of the segment height. Our simulation reveals that the glass transition is in synchronism with an abrupt change of the chain conformation in semiflexible polymer brushes. When the temperature drops to near Tg, the semiflexible polymer chains elongate, tilt, and become more ordered. Moreover, enhanced segmental dynamics is observed at temperatures just above Tg for the semiflexible polymer brushes.

An H-shaped [2]rotaxane comprising a bis(benzimidazole) axle and a 24-membered crown ether wheel appended with four trityl groups forms a highly crystalline material with enough free volume to allow large amplitude motion of the interlocked macrocycle. Variable-temperature (VT) 2H solid-state nuclear magnetic resonance (SSNMR) was used to characterize the dynamics of the [2]rotaxane wheel in this material.

In this publication, we generalize the proposed model of two interacting oscillators in the case of a strong difference in their periods (when the pacemaker pulses do not alternate) and propose a General model describing a network of oscillators coupled globally. Our goal is to make the model as simple as possible and enter the minimum number of parameters. Therefore, we will fully characterize the pacemaker of their internal lengths of the cycle and re-present them as pulse oscillators. Interaction of pacemakers is described by PRC

This work reports the first quantum-state-resolved collisional energy-transfer studies of supersonically cooled NO colliding with the surface of hot, molten Ga and detected by laser-induced fluores...

Customarily, the studies of dynamics of hydrated proteins are focused on the fast hydration water ν-relaxation, the slow structural α-relaxation responsible for a single glass transition, and the protein dynamic transition (PDT). Guided by the analogy with the dynamics of highly asymmetric mixtures of molecular glass-formers, we explore the possibility that the dynamics of hydrated proteins are richer than presently known. By providing neutron scattering, dielectric relaxation, calorimetry, and deuteron NMR data in two hydrated globular proteins, myoglobin and BSA, and the fibrous elastin, we show the presence of two structural α-relaxations, α1 and α2, and the hydration water ν-relaxation, all coupled together with interconnecting properties. There are two glass transition temperatures Tgα1and Tgα2 corresponding to vitrification of the α1 and α2 processes. Relaxation time τα2(T) of the α2-relaxation changes its Arrhenius temperature dependence to super-Arrhenius on crossing Tgα1 from below. The ν-relaxation responds to the two vitrifications by changing the T-dependence of its relaxation time τν(T) on crossing consecutively Tgα2 and Tgα1. It generates the PDT at Td where τν(Td) matches about five times the experimental instrument timescale τexp, provided that Td > Tgα1. This condition is satisfied by the hydrated globular proteins considered in this paper, and the ν-relaxation is in the liquid state with τν(T) having the super-Arrhenius temperature dependence. However, if Td < Tgα1, the ν-relaxation fails to generate the PDT because it is in the glassy state and τν(T) has Arrhenius T-dependence, as in the case of hydrated elastin. Overall, the dynamics of hydrated proteins are the same as the dynamics of highly asymmetric mixtures of glass-formers. The results from this study have expanded the knowledge of the dynamic processes and their properties in hydrated proteins, and impact on research in this area is expected.

Dendronized polymers (denpols) are thick polymers comprising a linear backbone with grafted treelike structures (dendrons). The latter give rise to a molecular thickness that is a function of dendr...

Well-dispersed polymer-tethered silica nanoparticles exhibit soft glassy rheology and caging behaviors due to chain interpenetration driven by entropic attraction and geometric confinement. In this...

Twisted internal charge transfer (TICT) states are of fundamental importance during the photo-physical processes of dyes and sensors. In this contribution, excited-state dynamics of an Al3+ fluorescence sensor 1-{[(2-hydroxyphenyl)-imino]methyl}naphthalen-2-ol based on the turn-on signal is clarified. Two different dark TICT states are observed by exploring the excited-state potential energy surface. With the twist of the C2-N bond, the two dark states can be reached facilely, which induce the experimentally observed weak fluorescence of the sensor. The sensing mechanism is then uncovered by investigating the electronic coupling between the sensor and analyte. Al3+ is proved to form strong coordination bonds with the sensor, which restricts the motion of the C2-N bond. Consequently, the TICT states are eliminated, which generate the turn-on signal. This sensing mechanism is trustworthy and intrinsically different from the previously proposed one, which would shed some light on the design of turn-on sensors.

Article presents data on the dynamics of blood pressure under the influence of the social environment and changes in diet, as well as the impact of various diseases.

Recently we have presented a theory of unification of gravitational and electromagnetic fields based on the generalization of Newton’s law to include a dynamic term similar to the Lorentz force of electrodynamics[1]. The unification is convincing. The generalization based on similarity of Newton’s law and Coulomb’s law, however, is speculative although reasonable and compelling. In this article, we have presented a derivation of the dynamic term of gravitation based on our newly proposed ether dynamics, which removes the speculative nature of dynamic term and perfects the unification theory. It turns out that the gravitational interaction is transmitted through the space medium ether. An object in ether is in direct contact with the ether, causing it to move like a highly viscous and incompressible fluid. The movement of ether propagates thorough space like a continuous medium, exerting a force on any object in ether.

YtvA from Bacillus subtilis is a sensor protein that responds to blue light stress and regulates the activity of transcription factor σB. It is composed of the N-terminal LOV (light-oxygen-voltage) domain, the C-terminal STAS (sulfate transporter and anti-sigma factor antagonist) domain, and a linker region connecting them. In this study, the photoreaction and kinetics of full-length YtvA and the intermolecular interaction with a downstream protein, RsbRA, were revealed by the transient grating method. Although N-YLOV-linker, which is composed of the LOV domain of YtvA with helices A'α and Jα, exhibits a diffusion change due to the rotational motion of the helices, the YtvA dimer does not show the diffusion change. This result suggests that the STAS domain inhibits the rotational movement of helices A'α and Jα. We found that the YtvA dimer formed a heterotetramer with the RsbRA dimer probably via the interaction between the STAS domains, and we showed the diffusion change upon blue light illumination with a time constant faster than 70 μs. This result suggests a conformational change of the STAS domains; i.e., the interface between the STAS domains of the proteins changes to enhance the friction with water by the rotation structural change of helices A'α and Jα of YtvA.

We have used non-extensive entropy to study the influence of the non-immunogenic tumor microenvironmental effects on dynamics of tumor growth. For this purpose, we have first employed the Tsallis and Abe entropies with different parameters. Then, we have applied the phenomenological model equation to determine the steady-state distribution for investigating tumor growth. Numerical results show that the steady-state distribution can change with some factors. We also plot this quantity versus the tumor population for studying the properties of steady state of tumor growth.

The millisecond timescale dynamics of activated Ras transiently sample a low-populated conformational state that has distinct surface property from the major state and represents a promising target for binding of small-molecule compounds. To avoid the complications of hydrolysis, dynamics and other properties of active Ras have so far been routinely investigated by using non-hydrolyzable GTP analogues, which, however, were previously reported to alter both the kinetics and distribution of the conformational exchange. In this study, we quantitatively measured and validated the internal dynamics of Ras complexed with a slowly hydrolyzable GTP analogue, GTPγS, which increases the lifetime of active Ras by 23 times relative to that of native GTP. It was found that GTPγS, in addition to its better mimicking of the exchange kinetics than the commonly used non-hydrolyzable analogues GppNHp and GppCH2 p, can rigorously reproduce the natural dynamics network in active Ras, thus indicating its fitness for use in the development of allosteric inhibitors.

Mitochondrial dynamics (fission and fusion) plays an important role in cell functions. Disruption in mitochondrial dynamics has been associated with diseases such as neurobiological disorders and cardiovascular diseases. Analysis of mitochondrial fission/fusion has been mostly achieved through direct visualization of the fission/fusion events in live-cell imaging of fluorescently labeled mitochondria. In this study, we demonstrated a label-free, non-invasive Electrical Impedance Spectroscopy (EIS) approach to analyze mitochondrial dynamics in a genetically modified human neuroblastoma SH-SY5Y cell line with no huntingtin protein expression. Huntingtin protein has been shown to regulate mitochondria dynamics. We performed EIS studies on normal SH-SY5Y cells and two independent clones of huntingtin-null cells. The impedance data was used to determine the suspension conductivity and further cytoplasmic conductivity and relate to the abnormal mitochondrial dynamics. For instance, the cytoplasm conductivity value was increased by 11% from huntingtin-null cells to normal cells. Results of this study demonstrated that EIS is sensitive to characterize the abnormal mitochondrial dynamics that can be difficult to quantify by the conventional microscopic method.

Drug discovery, in particular optimization of candidates using medicinal chemistry, is generally guided by structural biology. However, for optimizing binding kinetics, relevant for efficacy and off‐target effects, information on protein motion is important. Herein, we demonstrate for the prototypical textbook example of an allegedly “rigid protein” that substantial active‐site dynamics have generally remained unrecognized, despite thousands of medicinal‐chemistry studies on this model over decades. Comparing cryogenic X‐ray structures, solid‐state NMR on micro‐crystalline protein at room temperature, and solution NMR structure and dynamics, supported by MD simulations, we show that under physiologically relevant conditions the pocket is in fact shaped by pronounced open/close conformational‐exchange dynamics. The study, which is of general significance for pharmacological research, evinces a generic pitfall in drug discovery routines., Human carbonic anhydrase II (hCAII) plays an important role as a rigid model protein in medicinal chemistry. Under physiological conditions in solution, NMR spectroscopy combined with molecular dynamics simulations demonstrates that the active site shows pronounced open/close conformational exchange, undetected in crystallography‐based work.

The fluorescence blob model (FBM) was applied to analyze the fluorescence decays of a series of pyrene-labeled polypeptides to better understand how the amino acid (aa) composition of a polypeptide...

Recently, Hor et al. [Hor, J. L., Wang, H., Fakhraai, Z., & Lee, D. (2018). Macromolecules 51 (14), 5069–5078] reported a set of interesting results for the viscosity of unentangled polystyrene of ...

Residual dipolar couplings (RDCs) are commonly used in NMR for protein structure and dynamics studies, but it is challenging to generate five independent RDC data sets (required for simultaneous structure and dynamics determination) for most protein molecules in the magnetic field. In this work, a reporter protein with a lanthanide tag is introduced to create five independent alignments. This reporter protein is then attached to target proteins where five independent sets of RDCs are also obtained for the target proteins. The fitting of RDCs provides important information about the structure and dynamics of the target proteins. The method is simple and effective and, in principle, can be used to generate complete sets of RDCs for different protein molecules.

Experimental observations of two-stage autoignition dynamics of fiber-supported normal dodecane droplets in air under normal gravity are presented for a range of pressures and temperatures. High-sp...

Retrieving information about the molecular motion of polymer chain in melt from the FID is based on the theoretical assumptions in which the heterogeneity of segmental dynamics and its anisotropy along chain are ignored. This article—the second and conclusive in the series—demonstrates, in detail, the FID calculation for various length chains considering these peculiarities revealed in the previous article. The experimentally observed FID components are assigned to the corresponding fragments of the entangled chain, and reasons for the deviation from theoretical values defined by the chain structure are proposed.

In this study, we investigated the structural dynamic features of the [NH3(CH2)2NH3]ZnCl4 crystal as a function of temperature through magic angle spinning (MAS) 1H nuclear magnetic resonance (NMR), MAS 13C NMR, and static 14N NMR. From the chemical shifts, changes in the structural environments of 13C and 14N were evident. The 1H spin–lattice relaxation time (T1ρ) values at high temperatures undergo molecular motion according to the Bloembergen–Purcell–Pound theory, and the 13C T1ρ value also varied abruptly with increasing temperature. Although the phase-transition temperature was not detected from the differential scanning calorimetry result, the chemical shifts and T1ρ results showed discontinuities around 300 K. Herein, the activation energies of molecular motion for 1H and 13C obtained from T1ρ are discussed. In addition, we compare the structural dynamics of diammonium-type [NH3(CH2)2NH3]ZnCl4 obtained in this study and monoammonium-type [CH3NH3]2ZnCl4 previously reported. The findings reported herein can provide important insights for potential applications of [NH3(CH2)2NH3]ZnCl4 crystals.

The dynamic models of spherical and cylindrical pocket cages are established based on the dynamic wear simulation model of angular contact ball bearings, and the predicted results are in reasonable agreement with the experimental observations. In this paper, the effects of cage pocket shapes on dynamics of angular contact ball bearings in different pocket clearance are studied based on the established model. It is found that the whirl range of the cylindrical pocket cage is limited by guiding ring, and for spherical pocket cage is limited by balls. And the cage motion of spherical pocket is more stable than that of cylindrical pocket. The stability of the cage is positively related to the stability of the ball's distribution. Meanwhile, the axial swing range of the cage is related to the angle of the ball/cage pocket collision point. In addition, due to the sliding between the balls and the raceways, the bearing friction moment of the spherical pocket cage is larger, and the bearing friction moment of the cylindrical pocket cage is highly transient due to the unstable movement of the cage.

The dynamic heterogeneity of polymer chains is characterized by the lower correlation times of its end Kuhn segments with respect to those of the middle segments. In this study, the heterogeneity was investigated using molecular dynamics simulation of freely jointed chains of various lengths in the melt. Our characterization of the segmental dynamics along the chain additionally revealed the heterogeneity of rotational anisotropy, which was also lower for chain-end segments compared to those for chain-middle ones. This heterogeneity can be quantitatively characterized by intra-segmental residual dipolar coupling, which influences the transverse magnetic relaxation rate of the various chain segments and, ultimately, defines the free induction decay shape for chains of any length. Further, in the second part of this report, the origin of this relationship is discussed in detail.

Adefovir is regarded as a potential antiviral agent. However, it cannot be considered as a valuable drug candidate due to its high polarity that limits its permeability across the human intestinal mucosa. When the ribose phosphate group of adefovir is replaced by the isopolar phosphonomethyl ether functionality, it neutralizes the negative charge of the drug. This makes the drug lipid-soluble and potent to diffuse across the cell membrane. The prodrug adefovir dipivoxil is regarded as a potent antiviral drug against hepatitis B virus (HBV), human immunodeficiency virus (HIV), Rauscher murine leukemia virus (R-MuLV), murine cytomegalovirus (MCMV), herpes simplex virus (HSV), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). The correlation between the structure and the dynamics of adefovir dipivoxil is determined by measuring the principal components of chemical shift anisotropy (CSA) tensor, site-specific spin–lattice relaxation time, and molecular correlation time at crystallographically different carbon nuclei sites. The CSA parameters, spin–lattice relaxation time, and molecular correlation time of phosphorous nucleus of the organophosphate group of adefovir dipivoxil molecule are also determined. The spin–lattice relaxation time of carbon nuclei varies from 1 to 107 s. The range of molecular correlation time also varies from 10–4 to 10–8 s. These remarkable diversities of motional dynamics of the molecules imply that there exist various motional degrees of freedom within this valuable drug and these motional degrees of freedom are independent of each other, which may be the reason for the biological activities exhibited by the drug. The correlation between structure and dynamics of such an important antiviral drug adefovir dipivoxil can be visualized by these types of extensive spectroscopic measurements, which will enlighten the path of inventing advanced medicine in the pharmaceutical industry, and it will also illuminate the understanding of the structure–activity relationships of antiviral drug.

The modeling of low-temperature plasma synthesis of low-dimensional carbon coatings remains a challenge, since the long-time spans must be simulated for structural relaxation. A proper theoretical method should be chosen to address possible charge-transfer processes. Considering the possibility of linear-chained carbon (LCC) synthesis simulation, a numerical study of the C-C bond breaking under slow argon-ion irradiation is performed for the model molecules of 2,2,3,3-tetramethylbutane (sp3 hybridization), 1,2,3-butatriene (sp2), and 2-butyne (sp). Threshold energies of bond breaking are calculated for the carbon atoms in all three hybridizations. Three levels of theory are applied, and the results are compared with experiment. Based on the accuracy of the values obtained, an approach is proposed for modeling the ion-assisted plasma synthesis.

The dynamics of the HBr+ + CO2 → HOCO+ + Br reaction was recently investigated with guided ion beam experiments under various excitations (collision energy of the reactants, rotational and spin-orbital states of HBr+, etc.), and their impacts were probed through the change of the cross section of the reaction. The potential energy profile of this reaction has also been accurately characterized by high-level ab initio methods such as CCSD(T)/CBS, and the UMP2/cc-pVDZ/lanl08d has been identified as an ideal method to study its dynamics. This manuscript reports the first ab initio molecular dynamics simulations of this reaction at two different collision energies, 8.1 kcal/mol and 19.6 kcal/mol. The cross sections measured from the simulations agree very well with the experiments measured with HBr+ in the 2∏1/2 state. The simulations reveal three distinct mechanisms at both collision energies: direct rebound (DR), direct stripping (DS), and indirect (Ind) mechanisms. DS and Ind make up 97% of the total reaction. The dynamics of this reaction is also compared with nucleophilic substitution (SN2) reactions of X- + CH3Y → CH3X + Y- type. In summary, this research has revealed interesting dynamics of the HBr+ + CO2 → HOCO+ + Br reaction at different collision energies and has laid a solid foundation for using this reaction to probe the impact of rotational excitation of ion-molecule reactions in general.

Inflammatory diseases of periodontal tissues remain one of the most complex and unresolved problems of modern dentistry. The most important internal stimulus for triggering apoptosis is DNA damage in response to various factors (including reactive oxygen species). Mitochondrial transmembrane potential (Δψm) is generated by the electrochemical gradient of protons on both sides of the membrane and is closely related to the functioning of mitochondria, its support is provided by the processes of electron transfer in the respiratory chain. The purpose of our study was to elucidate the pathogenetic role of changes in mitochondrial transmebranic potential in the dynamics of the inflammatory response in experimental bacterial-immune periodontitis and the effects of quercetin (Korvityn) on it. Material and methods. The study was performed on white clinically healthy rats. Experimental bacterial-immune periodontitis in experimental animals was induced by injection of a mixture of microorganisms diluted with egg protein into the tissues of the periodontal complex. Quercetin was administered by intramuscular injection for correction. Evaluation of changes in mitochondrial transmembrane potential of leukocytes was performed by flow cytofluorimetry. Results and discussion. In experimental bacterial-immune periodontitis, the percentage of cells with reduced mitochondrial transmembrane potential among blood monocytes significantly increased. In animals on the 7th day of the study, the number of cells with reduced mitochondrial transmembrane potential among blood monocytes increased significantly compared with the control group. For the next study period (14th day), the number of cells with reduced ∆ψm decreased compared to the 7th day of the experiment. Having analyzed the data of mitochondrial transmembrane potential of blood monocytes on the 30th day of the experiment, we noted that they decreased relative to those obtained on the 14th day of the study, indicating profound oxidative imbalance in cells and destabilization of the mitochondrial membrane. The use of quercetin led to a decrease in the values compared to the data of animals with our simulated pathology on the 14th day, the experiment without the introduction of flavonol, but they remained significantly higher than the control group of animals. Conclusion. Flavonol (Korvityn) quercetin reduced mitochondrial transmembrane potential in experimental bacterial-immune periodontitis, which was evidence by stabilization and attenuation of the inflammatory process

Virus-like particles composed of the cowpea chlorotic mottle virus (CCMV) capsid protein (CP) have been extensively studied as carrier systems in nanoscience. One well-established method to improve their stability under physiological conditions is to fuse a stimulus-responsive elastin-like polypeptide (ELP) to the N-terminus of the CPs. Even though the N-terminus should in principle be localized in the inner cavity of the protein cage, studies on the native CCMV revealed its accessibility on the particle surface. We verified that such phenomenon also applies to ELP-CCMVs, by exploiting the covalent functionalization of the CP N-terminal domain via a sortase A-mediated reaction. Western-blot analysis and Forster resonance energy transfer (FRET) experiments furthermore revealed this to be caused by both the external display of the N-termini and the interchange of CPs among preformed capsids. Our findings demonstrate the tunability of ELP-CCMV stability and dynamics and their potential effect on the exploitation of such protein cages as a drug delivery system. This journal is

Ring polymers are a unique class of macromolecules that lack free ends and show qualitatively different dynamics compared to linear chains. Despite recent progress, the nonequilibrium flow behavior...

Molecular motions are fundamental to the existence of life, and NMR spectroscopy remains one of the most useful and powerful methods to measure their rates and molecular characteristics. Multiple experimental methods are available for measuring the NMR relaxation properties and these can require different methods for extracting model parameters. We present here a new software application, RING NMR Dynamics, that is designed to support analysis of multiple relaxation types. The initial release of RING NMR Dynamics supports the analysis of exponential decay experiments such as T1 and T2, as well as CEST and R2 and R1ρ relaxation dispersion. The software runs on multiple operating systems in both a command line mode and a user-friendly GUI that allows visualizing and simulating relaxation data. Interaction with another program, NMRFx Analyst, allows drilling down from the derived relaxation parameters to the raw spectral data.

Protein-tyrosine phosphatase 1B (PTP1B) is the canonical enzyme for investigating how distinct structural elements influence enzyme catalytic activity. Although it is recognized that dynamics are essential for PTP1B function, the data collected thus far have not resolved whether distinct elements are dynamically coordinated or, alternatively, whether they fulfill their respective functions independently. To answer this question, we performed a comprehensive (13)C-methyl relaxation study of Ile, Leu, and Val (ILV) residues of PTP1B, which, because of its substantially increased sensitivity, provides a comprehensive understanding of the influence of protein motions on different time scales for enzyme function. We discovered that PTP1B exhibits dynamics at three distinct time scales. First, it undergoes a distinctive slow motion that allows for the dynamic binding and release of its two most N-terminal helices from the catalytic core. Second, we showed that PTP1B (13)C-methyl group side chain fast time-scale dynamics and (15)N backbone fast time-scale dynamics are fully consistent, demonstrating that fast fluctuations are essential for the allosteric control of PTP1B activity. Third, and most importantly, using (13)C ILV constant-time Carr–Purcell–Meiboom–Gill relaxation measurements experiments, we demonstrated that all four catalytically important loops—the WPD, Q, E, and substrate-binding loops—work in dynamic unity throughout the catalytic cycle of PTP1B. Thus, these data show that PTP1B activity is not controlled by a single functional element, but instead all key elements are dynamically coordinated. Together, these data provide the first fully comprehensive picture on how the validated drug target PTP1B functions.

The paper presents results of an experimental study of the effect of pin microstructures on the wetting front propagation and its structure under adiabatic conditions and on strongly pre-heated surfaces, as well as the heat transfer and critical heat fluxes under steady-state heat release with liquid nitrogen film flowing. The surface structuring was created by the deformational cutting method (DCM). Comparison with data obtained on a smooth heater is presented. It is shown that the microstructures created by the DCM may have a significant effect on the nature of the temperature curves, reducing the total time of plate cooling at rewetting up to 2 times, and significantly change the structure and dynamics of the wetting front under adiabatic conditions. At the same time, such microstructuring with preset parameters of microfinning has weak influence on the heat transfer under steady-state heat release. High-speed video data of the processes are presented.

Nucleosomal histone H2A is exchanged for its variant H2A.Z by the SWR1 chromatin remodeler, but the mechanism and timing of histone exchange remain unclear. Here, we quantify DNA and histone dynamics during histone exchange in real-time using a three-color single-molecule FRET assay. We show that SWR1 operates with timed precision to unwrap DNA with large displacement from one face of the nucleosome, remove H2A-H2B from the same face, and rewrap DNA, all within 2.3 seconds. Such productive DNA unwrapping requires full SWR1 activation and differs from unproductive, smaller-scale DNA unwrapping caused by SWR1 binding alone. On an asymmetrically positioned nucleosome, SWR1 intrinsically senses long-linker DNA to preferentially exchange H2A.Z on the distal face as observed in vivo. The displaced H2A-H2B dimer remains briefly associated with the SWR1-nucleosome complex and is dissociated by histone chaperones. These findings reveal how SWR1 coordinates DNA unwrapping with histone dynamics to rapidly and accurately place H2A.Z at physiological sites on chromatin.One-Sentence SummaryMulticolor single-molecule FRET reveals how SWR1 unwraps DNA to exchange nucleosomal H2A-H2B for H2A.Z-H2B.

BackgroundThe crotonylation of histones is discovered of late as one of the post-translational modifications (PTMs) that can regulate gene expression. However, the function of crotonylation on nonhistone proteins in vascular smooth muscle cells (VSMCs) is unclear. Here, we aim to find the cellular characteristics of crotonylated nonhistone proteins and the cross talk with ubiquitinated proteins in VSMC phenotypic remodeling using the modified omics and proteomic analysis.MethodsWe performed the modified omics and proteomic analysis of VSMCs before and after the stimulation with platelet-derived growth factor-BB (PDGF-BB). The crotonylated and ubiquitinated pan-antibody was used to enrich proteins and then subjected to a high-throughput mass spectrometry analysis. The enrichment analysis was performed within differentially modified proteins in regard to GO terms, KEGG, and protein domains.ResultsAs a result, there were 2,138 crotonylation sites in 534 proteins and 1,359 ubiquitination sites corresponding to 657 proteins. These crotonylated proteins detected after PDGF-BB stimulation might be involved in various vital cellular pathways and carry out important functions in VSMCs. Some of them closely took part in significant physiological processes of VSMC phenotypic remodeling, including glycolysis/gluconeogenesis, vascular smooth muscle contraction, and the PI3K-Akt signaling pathway. Furthermore, the KEGG pathway enrichment analysis showed the involvement of ubiquitinated proteins in the physiological processes of VSMC phenotypic remodeling, including glycolysis/gluconeogenesis, vascular smooth muscle contraction, RAS signaling pathway, or the PI3K-Akt signaling pathway. A cross talk analysis showed that there were 199 sites within the 177 proteins modified by crotonylation and ubiquitination simultaneously. Protein–protein interaction (PPI) network analysis indicated that crotonylated and ubiquitinated proteins play an important role in cellular bioprocess commonly and possibly have a synergistic effect.ConclusionIn summary, our bioinformatics analysis shows that the crotonylation and ubiquitination of nonhistone proteins play an essential role in VSMC phenotypic transformation induced by PDGF-BB stimulation. The cross talk between crotonylation and ubiquitination in glycolysis is possibly a novel mechanism during VSMC phenotypic remodeling.

In this paper, two integrating strategies namely [-φ (χ)] and G′G2-expansion methods together with the attributes of local-M derivatives have been acknowledged on the electrical microtubule (MT) model to retrieve soliton solutions. The said model performs a significant role in illustrating the waves propagation in nonlinear systems. MTs are also highly productive in signaling, cell motility, and intracellular transport. The proposed algorithms yielded solutions of bright, dark, singular, and combo fractional soliton type. The significance of the fractional parameters of the fetched results is explained and presented vividly.

Although closely related genetically, bacterial strains belonging to the same species show significant variability in their growth and death dynamics. However, our understanding of the underlying processes that lead to this variability is still lacking. Here, we measured the growth and death dynamics of 11 strains of E. coli originating from different hosts and developed a mathematical model that captures their growth and death dynamics. Our model considers two environmental factors that determine growth dynamics: resource utilization efficiency and density-dependent growth inhibition. Here we show that both factors are required to capture the measured dynamics. Interestingly, our model results indicate that the main process that determines the major differences between the strains is the critical density at which they slow down their growth, rather than maximal growth rate or death rate. Finally, we found that bacterial growth and death dynamics can be reduced to only two dimensions and described by death rates and density-dependent growth inhibition alone.ImportanceUnderstanding the dynamics of bacterial growth has been an area of intense study. However, these dynamics have often been characterized through the narrow prism of describing growth rates, without considering parameters that may modulate these rates. Here, we generate a model that describes bacterial growth and death dynamics, incorporating two essential, growth-modulating factors: density-dependent reductions in growth rates and resource utilization efficiency. This model allows us to demonstrate that variation in the growth curves of closely related bacterial strains can be reduced to two dimensions and explained almost entirely by variation in the cellular density at which bacteria slow down their growth, combined with their death rates.