Bone is a complex tissue that fulfills the role of a resistance structure. This quality is most commonly assessed by bone densitometry, but bone strength may not only be related to bone mineral density but also to the preservation of bone cytoarchitectonics. The study included two groups of rats, ovariectomized and non-ovariectomized. Each group was divided into three batches: control, simvastatin-treated, and fenofibrate-treated. In the ovariectomized group, hypolipidemic treatment was instituted at 12 weeks post ovariectomy. One rat from each of the 6 batches was sacrificed 8 weeks after the start of treatment in the group. The experimental study was performed using a Bruker Minispec mq 20 spectrometer operating at a frequency of 20 MHz, subsequently also performed by H T-T molecular exchange maps. The results were represented by T-T molecular exchange maps that showed, comparatively, both pore size and their interconnectivity at the level of the femoral epiphysis, being able to evaluate both the effect of estrogen on bone tissue biology and the effect of the lipid-lowering medication, simvastatin, and fenofibrate, in both the presence and absence of estrogen. T-T molecular exchange maps showed that the absence of estrogen results in an increase in bone tissue pore size and interconnectivity. In the presence of estrogen, lipid-lowering medication, both simvastatin and fenofibrate alter bone tissue cytoarchitectonics by reducing pore interconnectivity. In the absence of estrogen, fenofibrate improves bone tissue cytoarchitectonics, the T-T molecular exchange map being similar to that of non-osteoporotic bone tissue.

Collective cell invasion underlies several biological processes such as wound healing, embryonic development, and cancerous invasion. Here, we investigate the impact of cell motility on invasion in epithelial monolayers and its coupling to cellular mechanical properties, such as cell-cell adhesion and cortex contractility. We develop a two-dimensional computational model for cells with active motility based on the cellular Potts model, which predicts that the cellular invasion speed is mainly determined by active cell motility and is independent of the biological and mechanical properties of the cells. We also find that, in general, motile cells out-compete and invade non-motile cells, however, this can be reversed by differential cell proliferation. Stable coexistence of motile and static cell types is also possible for certain parameter regimes.

External electric and mechanical stimuli can induce shape deformation in excitable media because of its intrinsic flexible property. When the signals propagation in the media is described by a neural network, creation of heterogeneity or defect is considered as the effect of shape deformation due to accumulation or release of energy in the media. In this paper, a temperature-light sensitive neuron model is developed from a nonlinear circuit composed of a phototube and a thermistor, and the physical energy is kept in capacitive and inductive terms. Furthermore, the Hamilton energy for this function neuron is obtained in theoretical way. A regular neural network is built on a square array by activating electric synapse between adjacent neurons, and a few of neurons in local area is excited by noisy disturbance, which induces local energy diversity, and continuous coupling enables energy propagation and diffusion. Initially, the Hamilton energy function for a temperature-light sensitive neuron can be obtained. Then, the finite neurons are applied noise to obtain energy diversity to explore the energy spread between neurons in the network. For keeping local energy balance, one intrinsic parameter is regulated adaptively until energy diversity in this local area is decreased greatly. Regular pattern formation indicates that local energy balance creates heterogeneity or defects and a few of neurons show continuous parameter shift for keeping energy balance in a local area, which supports gradient energy distribution for propagating waves in the network.

The evolutionary origin of the inverted retina in the vertebrate eye is unknown. This paper explores a hypothetical evolutionary scenario that explains the unique orientation of the photoreceptors in the vertebrate retina. The proposed scenario follows the scientific accepted scenario for eye evolution and gradually builds up towards an eye prototype by considering light direction detection and increase in achievable spatial resolution as the driving forces. It suggests that eye retinas developed along two different morphological processes, an evagination process that results in the inverted retina in vertebrate eyes and an invagination process that results in a verted retina in cephalopod eyes. The development of the inverted vertebrate retina and eye prototype morphology is strongly substantiated by physics of vision. The proposed evolutionary sequence for vertebrate eye development is simple and has the full potential to explain the origin of the inverted retina and leads to an eye prototype enabling visual detection and orientation. It allows the emergence of eye structures like, extraocular muscles, tapetum lucidum, biconvex lens, cornea, and pupil. This study supports the suggestion that a primitive inverted retina in the predecessor of vertebrates is of ectodermal origin and available before neurulation occurred.

During the asymmetric loop extrusion of DNA by a condensin complex, one domain of the complex stably anchors to the DNA molecule, and another domain reels in the DNA strand into a loop. The DNA strand in the loop is fully relaxed, or there is no tension in the loop. Just outside of the loop, there is a tension that resists the extrusion of DNA. To maintain the extrusion of the DNA loop, the condensin complex must have a domain capable of generating a force to overcome the tension outside of the loop. This study proposes that the groove-shaped HEAT repeat domain Ycg1 plays the role of a molecular motor. A DNA molecule may bind to the groove electrostatically, and the weak binding force facilitates the random thermal motion of DNA molecules. A mechanical model that random collisions between DNA and the nonparallel inner surfaces of the groove may generate a directional force which is required for the loop extrusion to sustain. The hinge domain binds to the DNA molecule and acts as an anchor during asymmetric DNA loop extrusion. When the effects of ATP hydrolysis and the viscous drag of the fluid environment are considered, the motor-anchor model for the condensin complex and the mechanical model might explain the asymmetric loop extrusion, the formation of steps, the step size distribution in the loop extrusion, the tension-dependent extrusion speed, the interaction between coexisting loops on the DNA strand, and untying the knots during extrusion. This model can also explain the observed formation of the Z-loop.

The exploration of microgravity has garnered substantial scholarly attention due to its potential to offer unique insights into the behavior of biological systems. This study presents a preliminary investigation into the effects of simulated microgravity on esophageal cancer cells, examining various aspects such as morphology, growth behavior, adhesion, inhibition rate, and DNA damage. To achieve this, a novel microgravity simulator named "Gravity Challenge" was utilized for its effectiveness in minimizing external influences that could compromise microgravity conditions. The international cell line SK-GT-4 was utilized as the focal point of this investigation. Results revealed noticeable alterations in the growth behavior of cancer cells following exposure to simulated microgravity for 24 h, characterized by a loss of adhesion properties compared to control cells. Concurrently, cell viability exhibited a decline, as evidenced by cytotoxicity testing. Furthermore, the comet assay test demonstrated that cells subjected to microgravity simulation experienced a higher incidence of DNA damage compared to their control counterparts. In conclusion, this comprehensive examination of the impact of simulated microgravity on esophageal cancer cells extends beyond morphological changes, delving into genetic implications through observed DNA damage. The diminished vitality of cells under microgravity conditions underscores the multifaceted effects on cellular behavior in response to environmental variations. These findings represent a significant step towards understanding the dynamics of cancer cells, laying the groundwork for future research aimed at identifying potential therapeutic strategies for this disease.

Bioconvective flows over a thin needle hold significant importance in various fields, particularly in biomedical engineering, microfluidics, and environmental science. This paper examines the bioconvective flow properties of a copper and blood-based Casson nanofluid over a thin needle, accounting for gyrotactic microorganisms in the presence of a magnetic field. The two-phase nanofluid model is applied to formulate the flow problem. The system of non-dimensional ordinary differential equations is obtained by reducing the governing partial differential equations with the help of similarity variables. Further, the ODEs are numerically solved using the 4th-order Runge-Kutta method based Shooting technique. The similar solutions of the non-dimensional ODEs are represented graphically and the blood-based nanofluid's velocity, temperature, concentration, and presence of microorganisms are examined with reference to the accompanying diagrams. A detailed analysis is provided for skin friction, Nusselt number, and microorganism density number. The primary outcomes reveal that the augmentation of the mixed convection parameter and buoyancy ratio parameter enhance the rate of heat transfer.

This study presents a stochastic model of seed dispersal based on a branching random walk (BRW) framework, incorporating both homogeneous and non-homogeneous Poisson point processes (PPP). Building on the model introduced by Coletti et al. (2023), we examine the effects of habitat reduction on seed dispersal dynamics. We analyze the phase transition behavior of the BRW model under varying conditions of habitat fragmentation, focusing on how these conditions influence the critical dispersal rate. Specifically, we study a BRW on the real line with a non-homogeneous PPP driven by a log-normal density, constrained between spatial barriers. Our simulations localize the critical dispersal rate with respect to barrier positions and compare this dependence between homogeneous and non-homogeneous models.

Cell fate decision is crucial in biological development and plays fundamental roles in normal development and functional maintenance of organisms. By identifying key regulatory interactions and molecules involved in these fate decisions, we can shed light on the intricate mechanisms underlying the cell fates. This understanding ultimately reveals the fundamental principles driving biological development and the origins of various diseases. In this study, we present an overarching framework which integrates pseudo-trajectory inference and differential analysis to determine critical regulatory interactions and molecules during cell fate transitions. To demonstrate feasibility and reliability of the approach, we employ the differentiation networks of hepatobiliary system and embryonic stem cells as representative model systems. By applying pseudo-trajectory inference to biological data, we aim to identify critical regulatory interactions and molecules during the cell fate transition processes. Consistent with experimental observations, the approach can allow us to infer dynamical cell fate decision processes and gain insights into the underlying mechanisms which govern cell state decisions.

In this paper, the dynamic behaviors of tuberculosis in the context of indirect environmental transmission are discussed by establishing the SEIRB epidemic model. The basic reproduction number is computed by employing the next-generation matrix approach. The global stability of disease-free equilibrium and endemic equilibrium is proved by constructing the Lyapunov function and the application of LaSalle's invariance principle. It shows that when the basic reproduction number is greater than 1, tuberculosis will spread among the population. When the basic reproduction number is less than 1, tuberculosis will disappear. Finally, an optimal control problem is constructed by using the extended model, which reveals the spread of tuberculosis can be effectively controlled by eliminating Mycobacterium tuberculosis in the environment and controlling tuberculosis patients at the same time. Numerical example results show the effectiveness of the optimization strategies.

Epilepsy is a type of brain disorder triggered by an abrupt electrical imbalance of neuronal networks. An electroencephalogram (EEG) is a diagnostic tool to capture the underlying brain mechanisms and detect seizure onset in epileptic patients. To detect seizures, neurologists need to manually monitor EEG recordings for long periods, which is challenging and susceptible to errors depending on expertise and experience. Therefore, automatic identification of seizure and seizure-free EEG signals becomes essential. This study introduces a method based on the features extracted from the phase space reconstruction for classifying seizure and seizure-free EEG signals. The computed features are derived from the elliptical area and interquartile range of the Euclidean distance by varying percentage values of data points ranging from 50 to 100%. We consider two public datasets and evaluate these features in each EEG epoch that includes the healthy, interictal, preictal, and ictal stages of epileptic subjects, utilizing the K-nearest neighbor classifier for classification. Results show that the features have higher values during the seizure than the seizure-free EEG signals and healthy subjects. Furthermore, the proposed features can effectively discriminate seizure EEG signals from the seizure-free and normal subjects with 100% accuracy, sensitivity, and specificity in both datasets. Likewise, the classification between the preictal stage and seizure EEG signals attains 98% accuracy. Overall, the reconstructed phase space features significantly enhance the accuracy of detecting epileptic EEG signals compared with existing methods. This advancement holds great potential in assisting neurologists in swiftly and accurately diagnosing epileptic seizures from EEG signals.

Time of day affects how well the immune system responds to viral or bacterial infections. While it is well known that the immune system is regulated by the circadian clock, the dynamic origin of time-of-day-dependent immunity remains unclear. In this paper, we studied the circadian control of immune response upon infection of influenza A virus through mathematical modeling. Dynamic simulation analyses revealed that the time-of-day-dependent immunity was rooted in the relative phase between the circadian clock and the pulse of viral infection. The relative phase, which depends on the time the infection occurs, plays a crucial role in the immune response. It can drive the immune system to one of two distinct bistable states, a high inflammatory state with a higher mortality rate or a safe state characterized by low inflammation. The mechanism we found here also explained why the same species infected by different viruses has different time-of-day-dependent immunities. Further, the time-of-day-dependent immunity was found to be abolished when the immune system was regulated by an impaired circadian clock with decreased oscillation amplitude or without oscillations.

The detection of magnetic fields by animals is known as magnetoreception. The ferromagnetic hypothesis explains magnetoreception assuming that magnetic nanoparticles are used as magnetic field transducers. Magnetite nanoparticles in the abdomen of Apis mellifera honeybees have been proposed in the literature as the magnetic field transducer. However, studies with ants and stingless bees have shown that the whole body of the insect contain magnetic material, and that the largest magnetization is in the antennae. The aim of the present study is to investigate the magnetization of all the body parts of honeybees as has been done with ants and stingless bees. To do that, the head without antennae, antennae, thorax, and abdomen obtained from Apis mellifera honeybees were analyzed using magnetometry and Ferromagnetic Resonance (FMR) techniques. The magnetometry and FMR measurements show the presence of magnetic material in all honeybee body parts. Our results present evidence of the presence of biomineralized magnetite nanoparticles in the honeybee abdomen and, for the first time, magnetite in the antennae. FMR measurements permit to identify the magnetite in the abdomen as biomineralized. As behavioral experiments reported in the literature have shown that the abdomen is involved in magnetoreception, new experimental approaches must be done to confirm or discard the involvement of the antennae in magnetoreception.

Studying the calcium dynamics within a fibroblast cell individually has provided only a restricted understanding of its functions. However, research efforts focusing on systems biology approaches for such investigations have been largely neglected by researchers until now. Fibroblast cells rely on signaling from calcium and nitric oxide (NO) to maintain their physiological functions and structural stability. Various studies have demonstrated the correlation between NO and the control of dynamics in cells. However, there is currently no existing model to assess the disruptions caused by various factors in regulatory dynamics, potentially resulting in diverse fibrotic disorders. A mathematical model has been developed to investigate the effects of changes in parameters such as buffer, receptor, sarcoplasmic endoplasmic reticulum -ATPase (SERCA) pump, and source influx on the regulation and dysregulation of spatiotemporal calcium and NO dynamics in fibroblast cells. This model is based on a system of reaction-diffusion equations, and numerical simulations are conducted using the finite element method. Disturbances in key processes related to calcium and nitric oxide, including source influx, buffer mechanism, SERCA pump, and inositol trisphosphate receptor, may contribute to deregulation in the calcium and NO dynamics within fibroblasts. The findings also provide new insights into the extent and severity of disorders resulting from alterations in various parameters, potentially leading to deregulation and the development of fibrotic disease.

We present a mathematical model that explores the progression of Alzheimer's disease, with a particular focus on the involvement of disease-related proteins and astrocytes. Our model consists of a coupled system of differential equations that delineates the dynamics of amyloid beta plaques, amyloid beta protein, tau protein, and astrocytes. Amyloid beta plaques can be considered fibrils that depend on both the plaque size and time. We change our mathematical model to a temporal system by applying an integration operation with respect to the plaque size. Theoretical analysis including existence, uniqueness, positivity, and boundedness is performed in our model. We extend our mathematical model by adding two populations, namely prion protein and amyloid beta-prion complex. We characterize the system dynamics by locating biologically feasible steady states and their local stability analysis for both models. The characterization of the proposed model can help inform in advancing our understanding of the development of Alzheimer's disease as well as its complicated dynamics. We investigate the global stability analysis around the interior equilibrium point by constructing a suitable Lyapunov function. We validate our theoretical analysis with the aid of extensive numerical illustrations.

Acyl-CoA dehydrogenase deficiency (ACAD) is an inherited and potentially fatal disorder with variable clinical symptoms. The relationship between pathogenicity and deleterious point mutations is investigated here in ACAD structures of short (SCAD) and medium-chain (MCAD) types. Structures and dynamic features of native and mutant forms of enzymes models were compared. A total of 2.88 µs molecular dynamics simulations were performed at four different temperatures. Total energy, RMSD, protein ligand interactions and affinity, RMSF measures, secondary structure changes, and important interactions were studied. Mutations in the three main domains of ACADs are pathogenic, while those located at linker turns are not. Mutations affect mostly tetramer formations, secondary structures, and many contacts and interactions. In R206H (MCAD mutant) which is experimentally known to cause a huge turnover decrease, the lack of a single H-bond between substrate and FAD was observed. Secondary structures showed temperature-dependent changes, and SCAD activity was found to be highly correlated to the enzyme helix 3-10 content. Finally, RMSF patterns pointed to one important loop that maintains the substrate close to the active site and is a cause of substrate wobbling upon mutation. Despite similar structure, function, and cellular location, SCAD and MCAD may have different optimum temperatures that are related to the structure taken at that specific temperature. In conclusion, new insight has been provided on the effect of various SCAD and MCAD pathogenic mutations on the structure and dynamical features of the enzymes.

Weakly reversible chemical reaction networks with zero deficiency associated with mass-action kinetics admit, within each positive stoichiometric compatibility class, one positive steady state which is locally asymptotically stable and this irrespective of the values of the kinetics constants. Networks which do not enjoy these structural properties potentially exhibit more diverse dynamical behaviors. In this article, we consider a chemical reaction network associated with mass-action kinetics which is not weakly reversible and has a deficiency larger than one. The chemical reactions are at most bimolecular, but inflow and outflow reactions are present. Our results are as follows. We establish the existence of positive steady-state solutions and obtain their analytic expressions in the concentration space and in convex coordinates. We show that the system fulfills necessary conditions for a saddle-node and for a bifurcation into a saddle and a node. We apply a constructive approach to obtain a set of numerical values for the state variables and kinetic parameters, not reported previously, such that the reduced Jacobian is characterized by a zero eigenvalue with all other eigenvalues having negative real parts. The bifurcation diagram confirms the presence of the switch-like behavior.

Methyl damage to DNA bases is common in the cell nucleus. O6-alkylguanine-DNA alkyl transferase (AGT) may be a promising candidate for direct damage reversal in methylated DNA (mDNA) at the O6 point of the guanine. Indeed, atomic-level investigations in the contact region of AGT-DNA complex can provide an in-depth understanding of their binding mechanism, allowing to evaluate the silico-drug nature of AGT and its utility in removing methyl damage in DNA. In this study, molecular dynamics (MD) simulation was utilized to examine the flipping of methylated nucleotide, the binding mechanism between mDNA and AGT, and the comparison of binding strength prior and post methyl transfer to AGT. The study reveals that methylation at the O6 atom of guanine weakens the hydrogen bond (H-bond) between guanine and cytosine, permitting for the flipping of such nucleotide. The formation of a H-bond between the base pair of methylated nucleotide (i.e., cytosine) and the intercalated arginine of AGT also forces the nucleotide to rotate. Following that, electrostatics and van der Waals contacts as well as hydrogen bonding contribute to form the complex of DNA and protein. The stronger binding of AGT with DNA before methyl transfer creates the suitable condition to transfer methyl adduct from DNA to AGT.

Melanoma is one of the most severe cancers due to its great potential to form metastasis. Recent studies showed the importance of mechanical property assessment in metastasis formation which depends on the cytoskeleton dynamics and cell migration. Although cells are considered purely elastic, they are viscoelastic entities. Microrheology atomic force microscopy (AFM) enables the assessment of elasticity and viscous properties, which are relevant to cell behavior regulation. The current work compares the mechanical properties of human neonatal primary melanocytes (HNPMs) with two melanoma cell lines (WM793B and 1205LU cells), using microrheology AFM. Immunocytochemistry of F-actin filaments and phosphorylated focal adhesion kinase (p-FAK) and cell migration assays were performed to understand the differences found in microrheology AFM regarding the tumor cell lines tested. AFM revealed that HNPMs and tumor cell lines had distinct mechanical properties. HNPMs were softer, less viscous, presenting a higher power-law than melanoma cells. Immunostaining showed that metastatic 1205LU cells expressed more p-FAK than WM793B cells. Melanoma cell migration assays showed that WM73B did not close the gap, in contrast to 1205LU cells, which closed the gap at the end of 23 h. These data seem to corroborate the high migratory behavior of 1205LU cells. Microrheology AFM applied to HNPMs and melanoma cells allowed the quantification of elasticity, viscous properties, glassy phase, and power-law properties, which have an impact in cell migration and metastasis formation. AFM study is important since it can be used as a biomarker of the different stages of the disease in melanoma.

Motile bacteria in hybrid nanofluids cause bioconvection. Bacillus cereus, Pseudomonas viscosa, Bacillus brevis, Salmonella typhimurium, and Pseudomonas fluorescens were used to evaluate their effect and dispersion in the hybrid nanofluid. Using similarity analysis, a two-phase model for mixed bioconvection magnetohydrodynamic flow was developed using hybrid nanoparticles of AlO and Cu (Cu-AlO/water). The parametric investigation, covering the magnetic parameter, permeability coefficient, nanoparticle shape factor, temperature ratio, radiation parameter, nanoparticle fraction ratio, Brownian parameter, thermophoresis parameter, motile bacteria diffusivity, chemotaxis parameter, and Nusselt, Reynold, Prandtl, Sherwood numbers, as well as the number of motile microorganisms', showed significant outcomes. Velocity and shear stresses are sensitive to M, Pr, and [Formula: see text]. Magnetic, radiation, and chemotaxis factors impact bacterial density. The hybrid nanofluid velocity decreases when the magnetic parameter, M, Prandtl number Pr increases, while it increases with the increasing of porosity coefficient, [Formula: see text], and the hybrid nanoparticle ratio N. The temperature distribution decreases with the increasing of Prandtl number and N. Increasing temperature differential and bacterium diffusivity increases bacterial aggregation.