Journal of Biological Physics最新文献

Abstract

The occurrence and development of tumors depend on a complex regulation by not only biochemical cues, but also biomechanical factors in tumor microenvironment. With the development of epigenetic theory, the regulation of biomechanical stimulation on tumor progress genetically is not enough to fully illustrate the mechanism of tumorigenesis. However, biomechanical regulation on tumor progress epigenetically is still in its infancy. Therefore, it is particularly important to integrate the existing relevant researches and develop the potential exploration. This work sorted out the existing researches on the regulation of tumor by biomechanical factors through epigenetic means, which contains summarizing the tumor epigenetic regulatory mode by biomechanical factors, exhibiting the influence of epigenetic regulation under mechanical stimulation, illustrating its existing applications, and prospecting the potential. This review aims to display the relevant knowledge through integrating the existing studies on epigenetic regulation in tumorigenesis under mechanical stimulation so as to provide theoretical basis and new ideas for potential follow-up research and clinical applications.

Graphical Abstract

Mechanical factors under physiological conditions stimulate the tumor progress through epigenetic ways, and new strategies are expected to be found with the development of epidrugs and related delivery systems.

Growth curve models play an instrumental role in quantifying the growth of biological processes and have immense practical applications across all disciplines. The most popular growth metric to capture the species fitness is the “Relative Growth Rate” in this domain. The different growth laws, such as exponential, logistic, Gompertz, power, and generalized Gompertz or generalized logistic, can be characterized based on the monotonic behavior of the relative growth rate (RGR) to size or time. Thus, in this case, species fitness can be determined truly through RGR. However, in nature, RGR is often non-monotonic and specifically bell-shaped, especially in the situation when a species is adapting to a new environment [1]. In this case, species may experience with the same fitness (RGR) for two different time points. The species precise growth and maturity status cannot be determined from this RGR function. The instantaneous maturity rate (IMR), as proposed by [2], helps to determine the correct maturity status of the species. Nevertheless, the metric IMR suffers from severe drawbacks; (i) IMR is intractable for all non-integer values of a specific parameter. (ii) The measure depends on a model parameter. The mathematical expression of IMR possesses the term “carrying capacity” which is unknown to the experimenter. (iii) Note that for identifying the precise growth status of a species, it is also necessary to understand its response when the populations are deflected from their equilibrium position at carrying capacity. This is an established concept in population biology, popularly known as the return rate. However, IMR does not provide information on the species deflection rate at the steady state. Hence, we propose a new growth measure connected with the species return rate, termed the “reverse of relative of relative growth rate” (henceforth, RRRGR), which is treated as a proxy for the IMR, having similar mathematical properties. Finally, we introduce a stochastic RRRGR model for specifying precise species growth and status of maturity. We illustrate the model through numerical simulations and real fish data. We believe that this study would be helpful for fishery biologists in regulating the favorable conditions of growth so that the species can reach a steady state with optimum effort.

Abstract

Alpha-2-macroglobulin (α₂M) is an essential antiproteinase that is widely distributed in human plasma. The present study was aimed at investigating the binding of a potential therapeutic dietary flavonol, morin, with human α₂M using a multi-spectroscopic and molecular docking approach. Recently, flavonoid-protein interaction has gained significant attention, because a majority of dietary bioactive components interact with proteins, thereby altering their structure and function. The results of the activity assay exhibited a 48% reduction in the antiproteolytic potential of α₂M upon interaction with morin. Fluorescence quenching tests unequivocally confirmed quenching in the fluorescence of α₂M in the presence of morin, conforming complex formation and demonstrating that the binding mechanism involves a dynamic mode of interaction. Synchronous fluorescence spectra of α₂M with morin showed perturbation in the microenvironment around tryptophan residues. Furthermore, structural changes were observed through CD and FT-IR, showing alterations in the secondary structure of α₂M induced by morin. FRET further supports the results of the dynamic mode of quenching. Moderate interaction is shown by binding constant values using Stern–Volmer’s fluorescence spectroscopy. Morin binds to α₂M at 298 K with a binding constant of 2.7 × 10⁴ M⁻¹, indicating the strength of the association. The α₂M-morin system was found to have negative ΔG values, which suggests that the binding process was spontaneous. Molecular docking also reveals the different amino acid residues involved in this binding process, revealing that the binding energy is -8.1 kcal/mol.

We show that recognizable neural waveforms are reproduced in the model described in previous work. In so doing, we reproduce close matches to certain observed, though filtered, EEG-like measurements in closed mathematical form, to good approximations. Such neural waves represent the responses of individual networks to external and endogenous inputs and are presumably the carriers of the information used to perform computations in actual brains, which are complexes of interconnected networks. Then, we apply these findings to a question arising in short-term memory processing in humans. Namely, we show how the anomalously small number of reliable retrievals from short-term memory found in certain trials of the Sternberg task is related to the relative frequencies of the neural waves involved. This finding justifies the hypothesis of phase-coding, which has been posited as an explanation of this effect.

Calcium ((Ca^{2+})), inositol trisphosphate ((IP_3)), and nitric oxide (NO) signaling are essential to maintain the structural integrity and physiological activity of fibroblast cells. The accumulation of excess quantity of NO for longer periods can lead to a variety of fibrotic disorders, including heart disease, penile fibrosis in Peyronie’s disease (PD), and cystic fibrosis. The dynamics of these three signaling processes and their interdependence in fibroblast cells are not clearly known to date. A systems biology model is proposed using reaction-diffusion equations for calcium, (IP_3), and calcium-dependent NO synthesis in fibroblast cells. The finite element method (FEM) is used to examine (Ca^{2+}), (IP_3), and NO regulation and dysregulation in cells. The results throw light on the conditions that disturb the coupled (Ca^{2+}) and (IP_3) dynamics and the influence of these factors on the levels of NO concentration in the fibroblast cell. The findings suggest that changes in source inflow, buffers, and diffusion coefficient might induce an increase or reduction in nitric oxide and (IP_3) synthesis, resulting in fibroblast cell diseases. Furthermore, the findings provide new information regarding the size and intensity of diseases in response to changes in several factors of their dynamics, which has been linked to the development of cystic fibrosis and cancer. This knowledge could be valuable for developing novel approaches to the diagnosis of diseases and therapies for various disorders of fibroblast cells.

Friction is ubiquitous but an essential force for insects during locomotion. Insects use dedicated bio-mechanical systems such as adhesive pads to modulate the intensity of friction, providing a stable grip with touching substrates for locomotion. However, how to uncover behavioral adaptation and regulatory neural circuits of friction modification is still largely understood. In this study, we devised a novel behavior paradigm to investigate adaptive behavioral alternation of Drosophila larvae under low-friction surfaces. We found a tail looseness phenotype similar to slipping behavior in humans, as a primary indicator to assess the degree of slipping. We found a gradual reduction on slipping level in wild-type larvae after successive larval crawling, coupled with incremental tail contraction, displacement, and speed acceleration. Meanwhile, we also found a strong correlation between tail looseness index and length of contraction, suggesting that lengthening tail contraction may contribute to enlarging the contact area with the tube. Moreover, we found a delayed adaptation in rut mutant larvae, inferring that neural plasticity may participate in slipping adaptation. In conclusion, our paradigm can be easily and reliably replicated, providing a feasible pathway to uncover the behavioral principle and neural mechanism of acclimation of Drosophila larvae to low-friction conditions.

A subgroup of T cells called T-regulatory cells (Tregs) regulates the body’s immune responses to maintain homeostasis and self-tolerance. Tregs are crucial for preventing illnesses like cancer and autoimmunity. However, contrasting patterns of Treg frequency are observed in different autoimmune diseases. The commonality of tumour necrosis factor receptor 2 (TNFR2) defects and decrease in Treg frequency on the onset of autoimmunity demands an in-depth study of the TNFR2 pathway. To unravel this mystery, we need to study the mechanism of cell survival and death in Tregs. Here, we construct an ordinary differential equation (ODE)-based model to capture the mechanism of cell survival and apoptosis in Treg cells via TNFR2 signalling. The sensitivity analysis reveals that the input stimulus, the concentration of tumour necrosis factor (TNF), is the most sensitive parameter for the model system. The model shows that the cell goes into survival or apoptosis via bistable switching. Through hysteretic switching, the system tries to cope with the changing stimuli. In order to understand how stimulus strength and feedback strength influence cell survival and death, we compute bifurcation diagrams and obtain cell fate maps. Our results indicate that the elevated TNF concentration and increased c-Jun N-terminal kinase (JNK) phosphorylation are the major contributors to the death of T-regulatory cells. Biological evidence cements our hypothesis and can be controlled by reducing the TNF concentration. Finally, the system was studied under stochastic perturbation to see the effect of noise on the system’s dynamics. We observed that introducing random perturbations disrupts the bistability, reducing the system’s bistable region, which can affect the system’s normal functioning.

Myricetin (MYR) is a bioactive secondary metabolite found in plants that is recognized for its nutraceutical value and is an essential constituent of various foods and beverages. It is reported to exhibit a plethora of activities, including antioxidant, antimicrobial, antidiabetic, anticancer, and anti-inflammatory. Alpha-2-macroglobulin (α2M) is a major plasma anti-proteinase that can inhibit proteinases of both human and non-human origin, regardless of their specificity and catalytic mechanism. Here, we explored the interaction of MYR-α2M using various biochemical and biophysical techniques. It was found that the interaction of MYR brings subtle change in its anti-proteolytic potential and thereby alters its structure and function, as can be seen from absorbance and fluorescence spectroscopy. UV spectroscopy of α2M in presence of MYR indicated the occurrence of hyperchromism, suggesting complex formation. Fluorescence spectroscopy reveals that MYR reduces the fluorescence intensity of native α2M with a shift in the wavelength maxima. At 318.15 K, MYR binds to α2M with a binding constant of 2.4 × 10³ M⁻¹, which indicates significant binding. The ΔG value was found to be − 7.56 kcal mol⁻¹ at 298.15 K, suggesting the interaction to be spontaneous and thermodynamically favorable. The secondary structure of α2M does not involve any major change as was confirmed by CD analysis. The molecular docking indicates that Asp-146, Ser-172, Glu-174, and Tyr-180 were the key residues involved in α2M-MYR complex formation. This study contributes to our understanding of the function and mechanism of protein and flavonoid binding by providing a molecular basis of the interaction between MYR and α2M.