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Conformational dynamics play a crucial role in protein functions. A molecular-level understanding of the conformational transition dynamics of proteins is fundamental for studying protein functions. Here, we report a study of real-time conformational dynamic interaction between calcium-activated calmodulin (CaM) and C28W peptide using single-molecule fluorescence resonance energy transfer (FRET) spectroscopy and imaging. Plasma membrane Ca-ATPase protein interacts with CaM by its peptide segment that contains 28 amino acids (C28W). The interaction between CaM and the Ca-ATPase is essential for cell signaling. However, details about its dynamic interaction are still not clear. In our current study, we used Cyanine3 labeled CaM (N-domain) and Dylight 649 labeled C28W peptide (N-domain) to study the conformational dynamics during their interaction. In this study, the FRET can be measured when the CaM-C28W complex is formed and only be observed when such a complex is formed. By using single-molecule FRET efficiency trajectory and unique statistical approaches, we were able to observe multiple binding steps with detailed dynamic features of loosely bound and tightly bound state fluctuations. The C-domain of CaM tends to bind with C28W first with a higher affinity, followed by the binding of the CaM N-domain. Due to the comparatively high flexibility and low affinity of the N-domain and the presence of multiple anchor hydrophobic residues on the peptide, the N-domain binding may switch between selective and non-selective binding states, while the C-domain remains strongly bound with C28W. The results provide a mechanistic understanding of the CaM signaling interaction and activation of the Ca-ATPase through multiple-state binding to the C28W. The new single-molecule spectroscopic analyses demonstrated in this work can be applied for broad studies of protein functional conformation fluctuation and protein-protein interaction dynamics.

Multiple endocytic pathways operate on the plasma membrane of cells at any moment with diverse but specific cellular functions. Knowledge of uptake of synthetic nanoparticles and ligands with respect to endocytic pathways is crucial to device the appropriate ligands for therapeutic delivery into differentiated neurons for targeting neuronal diseases. We herein explore the mechanisms of cellular uptake of 3D tetrahedral DNA nanocages at different stages of differentiating neurons. We monitored the uptake, kinetics, and dynamics of DNA cages of different geometries, and interestingly we find a specific pattern and adaptability of the uptake of DNA devices with respect to the geometry of the ligand and specific endocytic pathways. We find that tetrahedral DNA nanocages get endocytosed mostly via clathrin-mediated endocytosis in fully mature neurons. This endocytic uptake and intracellular choreography of DNA nanodevices will help us design the smartly targeted biotherapeutics for targeting neuronal disorders.

Understanding under which conditions conjugative plasmids encoding antibiotic resistance can invade bacterial communities in the gut is of particular interest to combat the spread of antibiotic resistance within and between animals and humans. We extended a one-compartment model of conjugation to a two-compartment model, to analyse how differences in plasmid dynamics in the gut lumen and at the gut wall affect the invasion of plasmids. We compared scenarios with one and two compartments, different migration rates between the lumen and wall compartments, and different population dynamics. We focused on the effect of attachment and detachment rates on plasmid dynamics, explicitly describing pair formation followed by plasmid transfer in the pairs. The parameter space allowing plasmid invasion in the one-compartment model is affected by plasmid costs and intrinsic conjugation rates of the transconjugant, but not by these characteristics of the donor. The parameter space allowing plasmid invasion in the two-compartment model is affected by attachment and detachment rates in the lumen and wall compartment, and by the bacterial density at the wall. The one- and two-compartment models predict the same parameter space for plasmid invasion if the conditions in both compartments are equal to the conditions in the one-compartment model. In contrast, the addition of the wall compartment widens the parameter space allowing invasion compared with the one-compartment model, if the density at the wall is higher than in the lumen, or if the attachment rate at the wall is high and the detachment rate at the wall is low. We also compared the pair-formation models with bulk-conjugation models that describe conjugation by instantaneous transfer of the plasmid at contact between cells, without explicitly describing pair formation. Our results show that pair-formation and bulk-conjugation models predict the same parameter space for plasmid invasion. From our simulations, we conclude that conditions at the gut wall should be taken into account to describe plasmid dynamics in the gut and that transconjugant characteristics rather than donor characteristics should be used to parameterize the models.

Protein machines undergo conformational motions to interact with and manipulate polymeric substrates. The Sec translocase promiscuously recognizes, becomes activated, and secretes >500 non-folded preprotein clients across bacterial cytoplasmic membranes. Here, we reveal that the intrinsic dynamics of the translocase ATPase, SecA, and of preproteins combine to achieve translocation. SecA possesses an intrinsically dynamic preprotein clamp attached to an equally dynamic ATPase motor. Alternating motor conformations are finely controlled by the γ-phosphate of ATP, while ADP causes motor stalling, independently of clamp motions. Functional preproteins physically bridge these independent dynamics. Their signal peptides promote clamp closing; their mature domain overcomes the rate-limiting ADP release. While repeated ATP cycles shift the motor between unique states, multiple conformationally frustrated prongs in the clamp repeatedly "catch and release" trapped preprotein segments until translocation completion. This universal mechanism allows any preprotein to promiscuously recognize the translocase, usurp its intrinsic dynamics, and become secreted. ispartof: CELL REPORTS vol:38 issue:6 ispartof: location:United States status: published

This article presents data on the effect of processing avocado fruit on the dynamics of physiological and biochemical processes during low-temperature storage. The aim was to explore the effect of processing Fuerte avocado fruit with ‘Agrokhit’, ‘KHAN-8’ and ‘Extrasol-90’ preparations on the dynamics of physiological and biochemical processes during storage. The effectiveness of the preparations on the change in physiological and biochemical processes during storage of avocado fruit was evaluated by the release of carbon dioxide during their respiration, by the activity of terminal oxidases and the hydrolysis of pectin substances. The respiration rate, the activity of terminal oxidases – catalase, peroxidase, phenol oxidase, tyrosinase – and the kinetics of the hydrolysis of protopectin and pectin depended on the type of preparation and the duration of storage. Processing avocado fruit with the examined preparations did not violate metabolism, which was regulated by change in the activity of terminal oxidases of the plant cells, a reduced respiration rate and the rate of hydrolysis of protopectin and pectin. As a result, there was an increase in the storage period and fruit ripening. To slow down the physiological and biochemical processes – to increase the duration of ripening and storage of avocado fruit – it is recommended that they be treated with chitin derivatives Agrokhit and KHAN-8.

We present an atomistic simulation scheme for the determination of the hydration number (h) of aqueous electrolyte solutions based on the calculation of the water dipole reorientation dynamics. In this methodology, the time evolution of an aqueous electrolyte solution generated from ab initio molecular dynamics simulations is used to compute the reorientation time of different water subpopulations. The value of h is determined by considering whether the reorientation time of the water subpopulations is retarded with respect to bulk‐like behavior. The application of this computational protocol to magnesium chloride (MgCl2) solutions at different concentrations (0.6–2.8 mol kg−1) gives h values in excellent agreement with experimental hydration numbers obtained using GHz‐to‐THz dielectric relaxation spectroscopy. This methodology is attractive because it is based on a well‐defined criterion for the definition of hydration number and provides a link with the molecular‐level processes responsible for affecting bulk solution behavior. Analysis of the ab initio molecular dynamics trajectories using radial distribution functions, hydrogen bonding statistics, vibrational density of states, water‐water hydrogen bonding lifetimes, and water dipole reorientation reveals that MgCl2 has a considerable influence on the hydrogen bond network compared with bulk water. These effects have been assigned to the specific strong Mg‐water interaction rather than the Cl‐water interaction., Ab initio molecular dynamics simulations are used to characterize the structural, vibrational, and dynamical properties of water in aqueous magnesium chloride (MgCl2) solutions, and to develop a methodology to compute the hydration number (h) of aqueous electrolytes from water reorientation dynamics. The application of this protocol gives h values of MgCl2 solutions in excellent agreement with experimental hydration numbers obtained using GHz‐to‐THz dielectric relaxation spectroscopy.

Perovskites are widely utilized either as a primary component or as a substrate in which the dynamics of charged oxygen vacancy defects play an important role. Current knowledge regarding the dynamics of vacancy mobility in perovskites is solely based upon volume- and/or time-averaged measurements. This impedes our understanding of the basic physical principles governing defect migration in inorganic materials. Here, we measure the ergodic and nonergodic dynamics of vacancy migration at the relevant spatial and temporal scales using time-resolved atomic force microscopy techniques. Our findings demonstrate that the time constant associated with oxygen vacancy migration is a local property and can change drastically on short length and time scales, such that nonergodic states lead to a dramatic increase in the migration barrier. This correlated spatial and temporal variation in oxygen vacancy dynamics can extend hundreds of nanometers across the surface in inorganic perovskites.

The acceleration of structural relaxation or physical aging by deformation, known as overaging, has been reported in experiments and simulations of polymer and colloid glasses, and correct accounti...

Continuation computations were performed to generate the S-curve as well as the flammability limit. Transient simulations using detailed fuel chemistry and transport models were conducted to reprod...

The propagation of premix methane/air flames in long half-open ducts with different inclination angles θ between the sidewall and the horizon was numerically investigated using the laminar model. The numerical result was compared with the experimental and theoretical ones to validate the numerical model. The results show that the numerical results are in good agreement with them. The investigation provides the basic understanding of the effects on changing the shape of the ducts to promote the premixed flame combustion. For methane/air, the position where the flame front begins to concave is pushed back with the increase in angle θ. The so-called "tulip" flame even disappeared, if the angle θ is bigger than one certain value. Moreover, the flame propagation speed and pressure are enhanced as the angle θ increases. In addition, the numerical simulation indicates that the burning gas creates an eddy near the tip of the flame, altering the flow field and causing the tulip flame to appear. However, with the angle θ increased, the flame propagation is restrained by the change in sidewalls, resulting in the different flow patterns to suppress the formation of tulip flames and promote flame combustion.

Changes in the glass transition dynamics caused by nanoconfinement reveal pronounced out-of-equilibrium features. Therefore, the confinement effects weaken with time. Using dielectric spectroscopy, we have investigated the impact of molecular weight on the equilibration kinetics of the studied polymer embedded within anodic aluminum oxide nanoporous templates. For our research, we have used poly(phenylmethyl siloxane) (PMPS) with low (Mw = 2530 g/mol) and high (Mw = 27,800 g/mol) molecular weight. We have found that the observed faster dynamics of the nanopore-confined systems weakens with time, and ultimately it is possible to regain the bulk-like mobility. The equilibration time increases by reducing the pore size and lowering the annealing temperature much below the glass transition temperature of the interfacial layer, Tg_interface. The experimental data analysis has also revealed that the molecular weight of the nanopore-confined polymer influences the recovery of the bulk segmental relaxation time, τα. Low-molecular-weight PMPS rearrange and reach denser packing of the polymer chains with greater ease than the high-molecular-weight one. Finally, we have also demonstrated that the molecular weight affects the relationship between the time constant characterizing the equilibration kinetics and the characteristic time of viscous flow in cylindrical channels of nanometer size.

The effect of droplet dynamics on electric output of a PVDF (Polyvinylidene fluoride) cantilever is investigated through conducting in-laboratory experiments towards the raindrop energy harvesting ...

The noncovalent intercalation of amphiphilic molecules in the lipid membrane can be exploited to modulate efficiently the physical status of the membrane. Such effects are largely employed in a range of applications, spanning from drug-delivery to therapeutics. In this context, we have very recently developed an intramembrane photo-actuator consisting of an amphiphilic azobenzene molecule, namely ZIAPIN2. The selective photo-isomerization occurring in the lipid bilayer induces a photo-triggered change in the membrane thickness and capacitance, eventually permitting to evoke light-induced neuronal firing both in vitro and in vivo. Here, we present a study on the dynamical perturbation in the lipid membrane caused by ZIAPIN2 and its vehicle solvent, dimethyl sulfoxide. Effects on the dynamics occurring in the picosecond time range and at the molecular level are probed using quasi-elastic neutron scattering. By coupling experiments carried out both on model membranes and intact cells, we found that DMSO leads to a general retardation of the dynamics within a more dynamically ordered landscape, a result that we attribute to the dehydration at the interface. On the other hand, ZIAPIN2 partitioning produces a general softening of the bilayer owing to its interaction with the lipids. These data are in agreement with our recent studies, which indicate that the efficacy of ZIAPIN2 in triggering cellular signalling stems from its ability to mechanically perturb the bilayer as a whole, by forming light-sensitive membrane spanning dimers.

Relaxation dynamics of unentangled polymer melts (with a chain length below N = 100 for polyethylene) can be studied by performing either Rouse mode or relaxation mode analysis, such as proper orth...

Structural organization of the microcirculatory bed and mast cells in the uterus of mature female Wistar rats (n=60) were examined every 2 h over 24 h. During night hours, many vessels characterized by intensive reaction to NADPH-diaphorase and endothelial NO synthase were detected in the endometrium, and the density of these vessels and mast cells was quite high. During the day and evening hours, the capillaries with high levels of enzymes involved in NO synthesis and mast cells were less numerous. NO directly regulating the diameter of arteries and the intensity of transcapillary exchange can act as a signal molecule in the temporal dynamics of the vasoceptive action of estrogens and their receptors in the uterus.

The coupling between electrons and protons and the long-range transport of protons play important roles throughout biology. Biomimetic systems derived from benzimidazole-phenol (BIP) constructs have been designed to undergo proton-coupled electron transfer (PCET) upon electrochemical or photochemical oxidation. Moreover, these systems can transport protons along hydrogen-bonded networks or proton wires through multiproton PCET. Herein, the nonequilibrium dynamics of both single and double proton transfer in BIP molecules initiated by oxidation are investigated with first-principles molecular dynamics simulations. Although these processes are concerted in that no thermodynamically stable intermediate is observed, the simulations predict that they are predominantly asynchronous on the ultrafast time scale. For both systems, the first proton transfer typically occurs ∼100 fs after electron transfer. For the double proton transfer system, typically the second proton transfer occurs hundreds of femtoseconds after the initial proton transfer. A machine learning algorithm was used to identify the key molecular vibrational modes essential for proton transfer: a slow, in-plane bending mode that dominates the overall inner-sphere reorganization, the proton donor–acceptor motion that leads to vibrational coherence, and the faster donor–hydrogen stretching mode. The asynchronous double proton transfer mechanism can be understood in terms of a significant mode corresponding to the two anticorrelated proton donor–acceptor motions, typically decreasing only one donor–acceptor distance at a time. Although these PCET processes appear concerted on the time scale of typical electrochemical experiments, attaching these BIP constructs to photosensitizers may enable the detection of the asynchronicity of the electron and multiple proton transfers with ultrafast two-dimensional spectroscopy. Understanding the fundamental PCET mechanisms at this level will guide the design of PCET systems for catalysis and energy conversion processes., Neural networks help predict important motions in bioinspired molecules when they undergo proton-coupled electron transfer comprising one or two proton transfers along a proton wire.

It is known that the level of calcium in the body is under the control of the thyroid gland, and the metabolism of collagen – the organic matrix of bone – depends on the concentration of hydroxyproline in blood plasma. Therefore, we considered it appropriate to study the effect of osteotropic agents used to correct bone defects in experimental animals on changes in calcitonin and hydroxyproline levels. To elucidate the biochemical mechanisms osteotropic influence of drugs on bone tissues studied changes in markers of bone metabolism and Са hormone levels dynamics in experimental research. The aim of the study: to investigate the effectiveness of osteoinductive materials for the reconstruction of bone defects. Object and methods of research. Osteoplastic properties of the materials were studied in a model of a bone defect of the femur of the diaphyseal zone in Wistar rats, four months old. Were formed 4 experimental groups: control group (intact animals) – 12 individuals; Group I – 14 animals, osteoplastic material «mp3 OsteoBiol» was used to heal the bone defect; Group II – 13 animals, filling the bone defect with platelet-rich plasma (PRP); Group III – 15 animals, in the augmentation of the bone defect used the composition «mp3 OsteoBiol + PRP». Alkaline phosphatase activity was determined by photometric unified method. Total acid phosphatase was determined by photometric optimized kinetic method. The mineralization index was calculated as the ratio of the activity of Alkaline Phosphatase / Acid Phosphatase enzymes. Determination of the concentration of hydroxyproline was performed photometrically and the content of calcitonin in the blood of animals was studied by enzyme-linked immunosorbent assay. Statistical processing of the obtained results was performed on a personal computer using the licensed programs «Microsoft Excel» and «Statistica». Research results and their discussion. As a result of the study, it was found that the lowest values of the concentration of calcitonin and hydroxyproline were studied in experimental animals of group III, where the bone defect was restored by our proposed composition. On day 60 of the study in animals of group III, where the healing of the bone defect occurred under the action of our proposed composition, the activity of alkaline phosphatase was equal to that of intact rats, p> 0.05, p1 , p2

Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl-amine class of inhibitors bind to M2 and disrupt and interact with the channel’s water network, providing insight into the critical properties that enable their effective inhibition in wildtype M2. In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel’s natural ability to stabilize an excess protonic charge and is thus acting as a hydronium-mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts.TOC Graphic

The aim of the present study was to evaluate the effect of 5 species of chymosin with different concentrations on the dynamics of the traits measured by mechanical lactodynamograph, characterizing the coagulation ability of buffalo milk. The coagulation properties of buffalo milk were evaluated on 420 milk samples taken during morning milking from whole milk. Five enzymes (MAXIREN 600, FROMASE 750, MAHIREN XDS, MAXIREN 180 and MAXIREN PREM P) were tested with 4 concentrations each and one control group with a standard, recommended by the manufacturer of the biosensor – mechanical lactodynamometer chymosin (Polo Trade – Computerized Renneting Meter, Italy). The effect of the concentration of each enzyme was determined by examining 20 milk samples. The use of enzymes at various concentrations resulted in substantial variation in the magnitude and direction of changes. Different chymosins with different concentrations actively affect the curd firmness. The shorter coagulation time will provide sufficient time for the curd firming time and its curd firmness. Over 50% of milk samples coagulate by 6 minutes. The effects of enzymes and their different concentrations on measurement were in different groups, which in our opinion was a good prerequisite for using the obtained data for modelling of the measurement process.

Significance Despite decades of intense studies on homeostasis, network properties undergoing homeostatic regulation remain elusive. Furthermore, whether diverse forms of homeostatic plasticity are simply redundant or serve distinct functions is unclear. Here, our data show that functional correlations are subject to homeostatic regulation, both in terms of average amplitude and their structure. A computational model demonstrates that synaptic scaling is essential for the restoration of correlations and network structure, whereas intrinsic plasticity is crucial for the recovery of firing rates after perturbations, suggesting that synaptic scaling and intrinsic plasticity distinctly contribute to homeostatic regulation., Homeostasis is indispensable to counteract the destabilizing effects of Hebbian plasticity. Although it is commonly assumed that homeostasis modulates synaptic strength, membrane excitability, and firing rates, its role at the neural circuit and network level is unknown. Here, we identify changes in higher-order network properties of freely behaving rodents during prolonged visual deprivation. Strikingly, our data reveal that functional pairwise correlations and their structure are subject to homeostatic regulation. Using a computational model, we demonstrate that the interplay of different plasticity and homeostatic mechanisms can capture the initial drop and delayed recovery of firing rates and correlations observed experimentally. Moreover, our model indicates that synaptic scaling is crucial for the recovery of correlations and network structure, while intrinsic plasticity is essential for the rebound of firing rates, suggesting that synaptic scaling and intrinsic plasticity can serve distinct functions in homeostatically regulating network dynamics.

The reactor dynamics of suspension polymerization of styrene has been studied in a specially designed unit controlled by a computer. It is found that the changes under control actions (measure of heating power and measure of stirrer shaft power) consistently describe the changes in the physical (relaxation) state of polymer–monomer particles. This phenomenon is proposed to be used to control the process.

We have used magnetization transfer NMR experiments to measure the exchange rate constant (kex) of the imino protons in the unbound, cocaine-bound, and quinine-bound forms of the cocaine-binding DNA aptamer. Both long-stem 1 (MN4) and short-stem 1 (MN19) variants were analyzed, corresponding to structures with a prefolded secondary structure and ligand-induced-folding versions of this aptamer, respectively. The kex values were measured as a function of temperature from 5 to 45°C to determine the thermodynamics of the base pair opening for MN4. We find that the base pairs close to the ligand-binding site become stronger upon ligand binding, whereas those located away from the binding site do not strengthen. With the buffer conditions used in this study, we observe imino 1H signals in MN19 not previously seen, which leads us to conclude that in the free form, both stem 2 and parts of stem 3 are formed and that the base pairs in stem 1 become structured or more rigid upon binding. This is consistent with the kex values for MN19 decreasing in both stem 1 and at the ligand-binding site. Based on the temperature dependence of the kex values, we find that MN19 is more dynamic than MN4 in the free and both ligand-bound forms. For MN4, ligand-binding results in the reduction of dynamics that are localized to the binding site. These results demonstrate that an aptamer in which the base pairs are preformed also experiences a reduction in dynamics with ligand binding.

We investigate the photodissociation of CH3Cl at 193.3 nm using the velocity map imaging technique in (CH3Cl)n clusters in comparison with isolated molecules. Our results for the isolated molecules...

To date, dynamics monitoring oxidative stress on time resolution in vivo has not been achieved due to the limitation of probes, causing the difficulty to comprehensively understand its biological b...

Establishing the dynamics of wetting film thinning and rupture during the bubbles attached on the coal surface is extremely important for flotation. However, studying the dynamics of bubble attachment from the molecular level using molecular dynamics simulation (MDS) has rarely been reported. In this work, the dynamics of bubble attachment at three different coal [low-rank coal (LRC), bituminous coal (BC), and anthracite coal (AC)] surfaces with varying degrees of coalification were studied using MDS. In the bubble attachment process, the wetting film between the bubble and coal surface gradually become thinner until it ruptures. By comparing the bubble attachment dynamics on three different coal surfaces, the results indicate that the bubble attachment rate on the surface with strong hydrophobicity is faster than that on the surface with weak hydrophobicity. Besides, the number of hydrogen bonds between the molecules of the wetting film is decreased with the attachment of bubbles; however, it is sharply decreased on the BC surface and slowly reduces on the LRC surface before the film rupture. At the same time, the radial distribution functions (RDFs) of hydrogen bonds in the wetting film at the moment of bubble attachment on the coal surface are analyzed, indicating that the peak intensity of the RDF decreases at the time of bubble attachment. The findings in this study may help to better comprehend the dynamics of bubble attachment, which is valuable for future design in practical applications.

Analysis of the X-ray beam-induced dynamics in oxide glasses probed by X-ray photon correlation spectroscopy is presented. The results offer the possibility to estimate true sample relaxation time by performing two measurements with different X-ray fluxes., Probing the microscopic slow structural relaxation in oxide glasses by X-ray photon correlation spectroscopy (XPCS) revealed faster than expected dynamics induced by the X-ray illumination. The fast beam-induced dynamics mask true slow structural relaxation in glasses and challenges application of XPCS to probe the atomic dynamics in oxide glasses. Here an approach that allows estimation of the true relaxation time of the sample in the presence of beam-induced dynamics is presented. The method requires two measurements either with different X-ray beam intensities or at different temperatures. Using numerical simulations it is shown that the slowest estimated true relaxation time is limited by the accuracy of the measured relaxation times of the sample. By analyzing the reported microscopic dynamics in SiO2, GeO2 and B2O3 glasses, it is concluded that the beam-induced dynamics show rich behavior depending on the sample.

Stress tolerance is one of the most prominent and interesting topics in biology since many macro- and micro-adaptations have evolved in resistant organisms that are worth studying. When it comes to...

Emerging biomedical evidences suggest that tumor has capacity not only to secrete immunesuppression but also attack effector cells. In this work, we present a delay model to study the dynamics of tumor, effector cells and TGF-β interaction with incorporation of tumor-derived macrophages for counterattack. The existence of stationary solutions of the model and their long time behaviors are obtained analytically. The analytical results reveal that tumor-free stationary solution is stable if the body cells do not proliferate excessively, and tumor-present stationary solution is asymptotically stable if the proliferation rate of effector cells is greater than its suppression by TGF-β otherwise is unstable. For an unstable scenario, we examine the sensitivity of model parameters to ascertain their role in tumor-immune escape. This effort indicates the reducing function for effector cells suppression and increasing functions for tumors elimination. The numerical results validate all the analytical results and reveal the optimum tumor elimination strategies with amplifying effect on effector cells performance.

Revealing the mechanisms underlying the intracellular calcium responses in vascular endothelial cells (VECs) induced by mechanical stimuli contributes to a better understanding for vascular diseases, including hypertension, atherosclerosis, and aneurysm. Combining with experimental measurement and Computational Fluid Dynamics simulation, we developed a mechanobiological model to investigate the intracellular [Ca2+] response in a single VEC being squeezed through narrow microfluidic channel. The time-dependent cellular surface tension dynamics was quantified throughout the squeezing process. In our model, the various Ca2+ signaling pathways activated by mechanical stimulation is fully considered. The simulation results of our model exhibited well agreement with our experimental results. By using the model, we theoretically explored the mechanism of the two-peak intracellular [Ca2+] response in single VEC being squeezed through narrow channel and made some testable predictions for guiding experiment in the future.

Conformationally flexible protein complexes represent a major challenge for structural and dynamical studies. We present herein a method based on a hybrid NMR/MD approach to characterize the complex formed between the disordered p53TAD1-60 and the metastasis-associated S100A4. Disorder-to-order transitions of both TAD1 and TAD2 subdomains upon interaction is detected. Still, p53TAD1-60 remains highly flexible in the bound form, with residues L26, M40, and W53 being anchored to identical hydrophobic pockets of the S100A4 monomer chains. In the resulting "fuzzy" complex, the clamp-like binding of p53TAD1-60 relies on specific hydrophobic anchors and on the existence of extended flexible segments. Our results demonstrate that structural and dynamical NMR parameters (cumulative Δδ, SSP, temperature coefficients, relaxation time, hetNOE) combined with MD simulations can be used to build a structural model even if, due to high flexibility, the classical solution structure calculation is not possible.

We investigate the mobility of polystyrene particles ranging from 100 to 790 nm in diameter in dilute and semidilute sodium polystyrene sulfonate (NaPSS) solutions using fluorescence microscopy. We tune the polymer conformations by varying the ionic strength of the solution. The nanoparticle mean-squared displacements evolve linearly with time at all time scales, indicating Fickian diffusive dynamics. In solutions of high ionic strength, chains adopt a random walk conformation and particle dynamics couple to the bulk zero-shear rate viscosity, according to the Stokes-Einstein picture. In solutions of low ionic strength, however, particle dynamics nonmonotonically deviate from bulk predictions as polymer concentration increases and are not accurately predicted by the available models. These nonmonotonic dynamics directly correlate with the non-Gaussianity in distributions of particle displacements, suggesting the emergence of a local confining length scale as polyelectrolyte concentration increases.

Purpose To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. Results Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. Conclusions The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to nonstandard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work.

Complexes formed among diverse proteins carry out versatile functions in nearly all physiological processes. Association rates which measure how fast proteins form various complexes are of fundamental importance to characterize their functions. The association rates are not only determined by the energetic features at binding interfaces of a protein complex but also influenced by the intrinsic conformational dynamics of each protein in the complex. Unfortunately, how this conformational effect regulates protein association has never been calibrated on a systematic level. To tackle this problem, we developed a multiscale strategy to incorporate the information on protein conformational variations from Langevin dynamic simulations into a kinetic Monte Carlo algorithm of protein-protein association. By systematically testing this approach against a large-scale benchmark set, we found the association of a protein complex with a relatively rigid structure tends to be reduced by its conformational fluctuations. With specific examples, we further show that higher degrees of structural flexibility in various protein complexes can facilitate the searching and formation of intermolecular interactions and thereby accelerate their associations. In general, the integration of conformational dynamics can improve the correlation between experimentally measured association rates and computationally derived association probabilities. Finally, we analyzed the statistical distributions of different secondary structural types on protein-protein binding interfaces and their preference to the change of association rates. Our study, to the best of our knowledge, is the first computational method that systematically estimates the impacts of protein conformational dynamics on protein-protein association. It throws lights on the molecular mechanisms of how protein-protein recognition is kinetically modulated.

The correlations present in the ionic liquids (ILs) are essential to interpret the ion association and dynamics processes. The correlated and uncorrelated ionic conductivities reported from two different types of experiments were calculated employing molecular dynamics methods by exercising appropriate care to obtain the diffusive regions. The ionic conductivity is found to be correlated with lifetimes of the ion-pair and ion-cage formation. In this study, the structure and dynamic properties of five cyclic ammonium-based ILs were investigated by comparing the experimental results with the calculated transport properties: (1) 1-allyl-1-methylpyrrolidinium, (2) 1-propyl-1-methylpyrrolidinum, (3) 1-methyl-1-allylpiperidinium, (4) 4-allyl-4-methylmorpholin-4-ium, and (5) 4-allyl-4-ethylmorpholin-4-ium with bis(trifluoromethanesulfonyl)imide anion as the common anion. We observed the linear relationship between the inverse of ion-pair lifetimes and ionic conductivities. The diffusion coefficients obtained from velocity autocorrelation functions follow a trend similar to that of the experiment as compared to mean square displacements (MSDs). The ionic conductivities from correlated MSD and current autocorrelation functions are compared to the ionic conductivities from the conductometer experiment. The time correlation functions of the ion-pair and ion-cage dynamics were calculated. The correlation functions were used to obtain the lifetimes. Pyrrolidinium-based ILs show lower lifetimes than other ILs, which correlates with the conductivity. Morpholinium-based ILs show higher interaction between ions than other ILs. This result supports the slower dynamics present in morpholinium-based ILs than in other ILs. In this work, our objective is to give atomic insight into the dynamics of IL, which could not be extracted from the experiment, and relate microscopic properties with macroscopic properties.

A dynamic model of a polymer chain is presented, in which the effects of viscoelasticity in the framework of the standard model of the linear body is taken into account. The general solution for the motion equation of the Fourier–Laplace components of the coordinates of the monomers of the polymer chain is obtained. The diffusion behavior of the center of mass of the polymer chain is analyzed for the relaxation dynamics of the system.

The paper presents the results of studying the possibility of controlling the links of hormonal regulation of the reproductive cycle of cattle using silicon dioxide in an ultra-dispersed form to increase fertilization during frontal insemination. The aim of the study was to analyze the effect of silicon dioxide UDPs when used in the scheme for synchronizing the sexual cycle of heifers on the dynamics of progesterone, FSH and LH and the fertilization of animals from frontal insemination. The studies were carried out on breeding age heifers of the red steppe breed. We formed two groups by 10 heifers – the control and the experimental one. In both groups, the synchronization of estrus was carried out by double application of estrophan. In the experimental group, the animals were simultaneously injected with estrophan with a solution of silicon dioxide ultra-dispersed particles in isotonic sodium chloride solution (dose of silicon dioxide 10 μg/kg). Blood for the determination of hormones was taken from heifers on the 1st, the 11th and 14th days of the experiment. All animals were inseminated frontally with deep-frozen semen by the rectocervical method. It was found that in the experimental and control groups, the dynamics of gonadotropins during the induced sexual cycle was similar; however, the LH level before insemination in heifers of the experimental group exceeded that in the control by 0.81 ng/ml (34.4%). Fertility of heifers in the experimental group was 70.0%, in the control – 50.0%. The effect of silicon dioxide in the UDP form on the dynamics of sex hormones and the fertility of heifers from frontal insemination during estrus synchronization was studied for the first time.

Three series of pyrene-labeled polypeptides, namely, poly(l-lysine) (Py-PLL), poly(l-glutamic acid) (Py-PLGA), and poly(d,l-glutamic acid) (Py-PDLGA), were studied in dimethyl sulfoxide (DMSO) by m...

We present the first-principles molecular dynamics simulations of water molecules using two different levels of density functional theory within the Kohn-Sham scheme, namely, Becke-Lee-Yang-Parr (BLYP) and Perdew-Burke-Ernzerhof (PBE) with dispersion corrections such as D2 as well as D3 versions of Grimme dispersion correction and dispersion-corrected atom-centered potential. Our aim is to provide a comparative study of these functionals in explaining the thermophysical and structural properties along with nondiffusive jump dynamics of water molecules concerning the experimental data. The hydrogen bonding phenomenon is dependent on polarity, bonding, as well as nonbonding interactions, which requires thorough parametrization. Since hydrogen bonding is responsible for several properties in the water, we investigate the effect of dispersion corrections on the hydrogen bond jump dynamics. BLYP and PBE functionals are well-known for overestimating the spatial structure and underestimating the density and diffusivity. Thus, dispersion corrections are introduced to generate a well-structured and adequately dense equilibrated liquid water system. Here, we have reported the density values of water obtained from different density functionals and also verified the trend with other thermophysical phenomena such as compressibility and cohesive energy. The behavior of simulated water systems is further explained by analyzing various structural properties and hydrogen bond jump dynamics.

In this paper, we report a transient absorption microscopy study of photocarrier dynamics in CuS crystals at room temperature. The photocarriers are injected into the sample by interband absorption...

A variant of the Peyrard-Bishop-Dauxois model is proposed, which takes account of the partially delocalized nature of DNA stacking interactions. It is shown that the nonlocal nature of the inter-site potential can lead to an increase in the local cooperativity of the base pairs' opening an increasing in the number of simultaneously opening adjacent nucleotide pairs during the denaturation bubble's nucleation. The process of the formation and propagation of mobile breathers excited by the initial displacements of a number of nucleotide pairs has been studied. It is revealed that taking account of the non-local coupling in the Peyrard-Bishop-Dauxois model, while maintaining the remaining parameters of the model, leads to a decrease in the speed of the mobile breather and an increase in the probability of nucleation of the denaturation bubble.

The determination of thermal and vibrational relaxation rates of triatomic systems suitable for application in hypersonic model calculations is discussed. For this, potential energy surfaces for ground and electronically excited state species need to be computed and represented with high accuracy and quasiclassical or quantum nuclear dynamics simulations provide the basis for determining the relevant rates. These include thermal reaction rates, state-to-state cross-sections, or vibrational relaxation rates. For exemplary systems - [NNO], [NOO], and [CNO] - all individual steps are described and a literature overview for them is provided. Finally, as some of these quantities involve considerable computational expense, for the example of state-to-state cross sections the construction of an efficient model based on neural networks is discussed. All such data is required and being used in more coarse-grained computational fluid dynamics simulations., Review article, 46 pages, 8 figures

The effects of interphase topology, entanglements, and chain dynamics on the mechanical response of semicrystalline polyethylene have been examined using atomistic simulations. In particular, the prevalence of the cavitation and melting/recrystallization mechanisms for yield and plastic flow were found to depend on both topological and dynamical properties of the molecular segments in the semicrystalline interphase. First, two different protocols were used during preparation of the interphase ensemble to modulate the distribution of (i) loops, bridges, and tails and (ii) entanglements within the noncrystalline domain. A protocol denoted “step-wise cooling” produced structures having a large fraction of long, entangled segments that yielded by the melting/recrystallization mechanism about 50% of the time. By contrast, the protocol denoted “instantaneous quench” produced structures that yielded by melting/recrystallization about 73% of the time. Second, two different united atom force fields, PYS and TraPPE-UA, that exhibit nearly identical topological characteristics of the noncrystalline domain but different mobilities were used to study the effect of chain dynamics on yield mechanisms. At the slower strain rate used in this work, yield and plastic flow proceeded exclusively via cavitation for the model using the TraPPE-UA force field, whereas both cavitation and melting/recrystallization were observed for the model using the PYS force field. The greater prevalence of melting/recrystallization in the latter case is attributed to faster chain-sliding dynamics in the crystalline domain. The dependences of the yield mechanism on topology and dynamics are found to be related. ISSN:1520-5835 ISSN:0024-9297