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Scientific Reports Sep 2023Due to the unrestricted movement of humans over a wide area, it is important to understand how individuals move between non-adjacent locations in space. In this...
Due to the unrestricted movement of humans over a wide area, it is important to understand how individuals move between non-adjacent locations in space. In this research, we introduce a nonlocal diffusion introduce for dengue, which is driven by integral operators. First, we use the semigroup theory and continuously Fréchet differentiable to demonstrate the existence, uniqueness, positivity and boundedness of the solution. Next, the global stability and uniform persistence of the system are proved by analyzing the eigenvalue problem of the nonlocal diffusion term. To achieve this, the Lyapunov function is derived and the comparison principle is applied. Finally, numerical simulations are carried out to validate the results of the theorem, and it is revealed that controlling the disease's spread can be achieved by implementing measures to reduce the transmission of the virus through infected humans and mosquitoes.
Topics: Animals; Humans; Culicidae; Diffusion; Movement; Dengue
PubMed: 37709860
DOI: 10.1038/s41598-023-42440-3 -
The Journal of Physical Chemistry. B May 2024G protein-coupled receptors (GPCRs) are a major gateway to cellular signaling, which respond to ligands binding at extracellular sites through allosteric conformational...
G protein-coupled receptors (GPCRs) are a major gateway to cellular signaling, which respond to ligands binding at extracellular sites through allosteric conformational changes that modulate their interactions with G proteins and arrestins at intracellular sites. High-resolution structures in different ligand states, together with spectroscopic studies and molecular dynamics simulations, have revealed a rich conformational landscape of GPCRs. However, their supramolecular structure and spatiotemporal distribution is also thought to play a significant role in receptor activation and signaling bias within the native cell membrane environment. Here, we applied single-molecule fluorescence techniques, including single-particle tracking, single-molecule photobleaching, and fluorescence correlation spectroscopy, to characterize the diffusion and oligomerization behavior of the muscarinic M receptor (MR) in live cells. Control samples included the monomeric protein CD86 and fixed cells, and experiments performed in the presence of different orthosteric MR ligands and of several compounds known to change the fluidity and organization of the lipid bilayer. M receptors exhibit Brownian diffusion characterized by three diffusion constants: (∼0.01 μm/s), (∼0.04 μm/s), and (∼0.14 μm/s), whose populations were found to be modulated by both orthosteric ligands and membrane disruptors. The lipid raft disruptor C6 ceramide led to significant changes for CD86, while the diffusion of MR remained unchanged, indicating that M receptors do not partition in lipid rafts. The extent of receptor oligomerization was found to be promoted by increasing the level of expression and the binding of orthosteric ligands; in particular, the agonist carbachol elicited a large increase in the fraction of MR oligomers. This study provides new insights into the balance between conformational and environmental factors that define the movement and oligomerization states of GPCRs in live cells under close-to-native conditions.
Topics: Ligands; Receptor, Muscarinic M1; Diffusion; Humans; Cell Membrane; Protein Multimerization; Animals; Spectrometry, Fluorescence; Molecular Dynamics Simulation; Lipid Bilayers
PubMed: 38683784
DOI: 10.1021/acs.jpcb.4c01035 -
Soft Matter Oct 2023The lateral diffusion of cell membrane inclusions, such as integral membrane proteins and bound receptors, drives critical biological processes, including the formation...
The lateral diffusion of cell membrane inclusions, such as integral membrane proteins and bound receptors, drives critical biological processes, including the formation of complexes, cell-cell signaling, and membrane trafficking. These diffusive processes are complicated by how concentrated, or "crowded", the inclusions are, which can occupy between 30-50% of the area fraction of the membrane. In this work, we elucidate the effects of increasing concentration of model membrane inclusions in a free-standing artificial cell membrane on inclusion diffusivity and the apparent viscosity of the membrane. By multiple particle tracking of fluorescent microparticles covalently tethered to the bilayer, we show the transition from expected Brownian dynamics, which accurately measure the membrane viscosity, to subdiffusive behavior with decreased diffusion coefficient as the particle area fraction increases from 1% to around 30%, approaching physiological levels of crowding. At high crowding, the onset of non-Gaussian behavior is observed. Using hydrodynamic models relating the 2D diffusion coefficient to the viscosity of a membrane, we determine the apparent viscosity of the bilayer from the particle diffusivity and show an increase in the apparent membrane viscosity with increasing particle area fraction. However, the scaling of this increase is in contrast with the behavior of monolayer inclusion diffusion and bulk suspension rheology. These results demonstrate that physiological levels of model membrane crowding nontrivially alter the dynamics and apparent viscosity of the system, which has implications for understanding membrane protein interactions and particle-membrane transport processes.
Topics: Membranes; Membrane Proteins; Molecular Dynamics Simulation; Biophysical Phenomena; Diffusion; Membranes, Artificial; Viscosity
PubMed: 37791427
DOI: 10.1039/d3sm01269g -
Magnetic Resonance in Medicine Nov 2023We hypothesized that the time-dependent diffusivity at short diffusion times, as measured by oscillating gradient spin echo (OGSE) diffusion MRI, can characterize tissue...
PURPOSE
We hypothesized that the time-dependent diffusivity at short diffusion times, as measured by oscillating gradient spin echo (OGSE) diffusion MRI, can characterize tissue microstructures in glioma patients.
THEORY AND METHODS
Five adult patients with known diffuse glioma, including two pre-surgical and three with new enhancing lesions after treatment for high-grade glioma, were scanned in an ultra-high-performance gradient 3.0T MRI system. OGSE diffusion MRI at 30-100 Hz and pulsed gradient spin echo diffusion imaging (approximated as 0 Hz) were obtained. The ADC and trace-diffusion-weighted image at each acquired frequency were calculated, that is, ADC (f) and TraceDWI (f).
RESULTS
In pre-surgical patients, biopsy-confirmed solid enhancing tumor in a high-grade glioblastoma showed higher and lower , compared to that at same OGSE frequency in a low-grade astrocytoma. In post-treatment patients, the enhancing lesions of two patients who were diagnosed with tumor progression contained more voxels with high and low , compared to the enhancing lesions of a patient who was diagnosed with treatment effect. Non-enhancing T signal abnormality lesions in both the pre-surgical high-grade glioblastoma and post-treatment tumor progressions showed regions with high and low , consistent with infiltrative tumor. The solid tumor of the glioblastoma, the enhancing lesions of post-treatment tumor progressions, and the suspected infiltrative tumors showed high diffusion time-dependency from 30 to 100 Hz, consistent with high intra-tumoral volume fraction (cellular density).
CONCLUSION
Different characteristics of OGSE-based time-dependent diffusivity can reveal heterogenous tissue microstructures that indicate cellular density in glioma patients.
Topics: Adult; Humans; Glioblastoma; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging; Glioma; Image Interpretation, Computer-Assisted; Diffusion
PubMed: 37335831
DOI: 10.1002/mrm.29758 -
Journal of the Mechanical Behavior of... Jan 2024Hydrogels are a promising class of material in biomedical and industrial applications, where both the mechanical and diffusion properties play an important role. The...
Hydrogels are a promising class of material in biomedical and industrial applications, where both the mechanical and diffusion properties play an important role. The wide range of polymers that can be used and the different production methods allows these properties to be specifically tuned to a high degree for their application. Producing tough hydrogels with high stiffness has been a long-standing challenge that has recently been addressed by mineralisation methods. Those methods modify the hydrogel into one with a supporting mineral microstructure that is highly heterogeneous. This work investigates methods to determine the macroscopic diffusion behaviour of heterogeneous gels by a homogenisation method implemented in a finite element framework. This is applied to two recently developed materials by calcifying poly-dimethyl-acrylamide (PDMA) and polyacrylamide hydrogels (PAAm). The former has porous, spherical inclusions obstructing diffusion, while the latter has spherical pores enabling it. For both gels the unobstructed volume can be used as the primary parameter to tune the diffusivity. In PDMA the porosity of the obstructions is shown by multiscale analysis to give a strong, non-linear dependence of the diffusivity on the solute molecule radius. The framework is extended to other materials and comparisons are made to experimental works from the literature.
Topics: Hydrogels; Polymers; Calcification, Physiologic; Porosity; Diffusion
PubMed: 37988844
DOI: 10.1016/j.jmbbm.2023.106244 -
Beyond analytic solution: Analysis of FRAP experiments by spatial simulation of the forward problem.Biophysical Journal Sep 2023Fluorescence redistribution after photobleaching is a commonly used method to understand the dynamic behavior of molecules within cells. Analytic solutions have been...
Fluorescence redistribution after photobleaching is a commonly used method to understand the dynamic behavior of molecules within cells. Analytic solutions have been developed for specific, well-defined models of dynamic behavior in idealized geometries, but these solutions are inaccurate in complex geometries or when complex binding and diffusion behaviors exist. We demonstrate the use of numerical reaction-diffusion simulations using the Virtual Cell software platform to model fluorescence redistribution after photobleaching experiments. Multiple simulations employing parameter scans and varying bleaching locations and sizes can help to bracket diffusion coefficients and kinetic rate constants in complex image-based geometries. This approach is applied to problems in membrane surface diffusion as well as diffusion and binding in cytosolic volumes in complex cell geometries. In addition, we model diffusion and binding within phase-separated biomolecular condensates (liquid droplets). These are modeled as spherical low-affinity binding domains that also define a high viscosity medium for exchange of the free fluorescently labeled ligand with the external cytosol.
Topics: Diffusion; Fluorescence; Fluorescence Recovery After Photobleaching
PubMed: 37353932
DOI: 10.1016/j.bpj.2023.06.013 -
International Journal of Molecular... Aug 2023The mixed ionic and electronic oxide LaNiFeO (LNF) is a promising ceramic cathode material for solid oxide fuel cells. Since the reaction rate of oxygen interaction with...
The mixed ionic and electronic oxide LaNiFeO (LNF) is a promising ceramic cathode material for solid oxide fuel cells. Since the reaction rate of oxygen interaction with the cathode material is extremely important, the present work considers the oxygen exchange mechanism between O and LNF oxide. The kinetic dependence of the oxygen/oxide interaction has been determined by two isotopic methods using O-labelled oxygen. The application of the isotope exchange with the gas phase equilibrium (IE-GPE) and the pulsed isotope exchange (PIE) has provided information over a wide range of temperatures (350-800 °C) and oxygen pressures (10-200 mbar), as each method has different applicability limits. Applying mathematical models to treat the kinetic relationships, the oxygen exchange rate (, atom × cm × s) and the diffusion coefficient (, cm/s) were calculated. The values of and depend on both temperature and oxygen pressure. The activation energy of the surface exchange rate is 0.73 ± 0.05 eV for the PIE method at 200 mbar, and 0.48 ± 0.02 eV for the IE-GPE method at 10-20 mbar; for the diffusion coefficient, the activation energy equals 0.62 ± 0.01 eV at 10-20 mbar for the IE-GPE method. Differences in the mechanism of oxygen exchange and diffusion on dense and powder samples are observed due to the different microstructure and surface morphology of the samples. The influence of oxygen pressure on the ratio of contributions of different exchange types to the total oxygen exchange rate is demonstrated. For the first time, the rate-determining step in the oxygen exchange process for LNF material has been identified. This paper discusses the reasons for the difference in the mechanisms of oxygen exchange and diffusion.
Topics: Oxygen; Gases; Ceramics; Diffusion; Oxides
PubMed: 37629194
DOI: 10.3390/ijms241613013 -
Bioinformatics (Oxford, England) Dec 2023Microbiota data encounters challenges arising from technical noise and the curse of dimensionality, which affect the reliability of scientific findings. Furthermore,...
MOTIVATION
Microbiota data encounters challenges arising from technical noise and the curse of dimensionality, which affect the reliability of scientific findings. Furthermore, abundance matrices exhibit a zero-inflated distribution due to biological and technical influences. Consequently, there is a growing demand for advanced algorithms that can effectively recover missing taxa while also considering the preservation of data structure.
RESULTS
We present mb-PHENIX, an open-source algorithm developed in Python that recovers taxa abundances from the noisy and sparse microbiota data. Our method infers the missing information of count matrix (in 16S microbiota and shotgun studies) by applying imputation via diffusion with supervised Uniform Manifold Approximation Projection (sUMAP) space as initialization. Our hybrid machine learning approach allows to denoise microbiota data, revealing differential abundance microbes among study groups where traditional abundance analysis fails.
AVAILABILITY AND IMPLEMENTATION
The mb-PHENIX algorithm is available at https://github.com/resendislab/mb-PHENIX. An easy-to-use implementation is available on Google Colab (see GitHub).
Topics: Reproducibility of Results; Microbiota; Algorithms; Machine Learning; Diffusion
PubMed: 38015858
DOI: 10.1093/bioinformatics/btad706 -
Journal of Visualized Experiments : JoVE Aug 2023We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell cultures. The...
We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell cultures. The clinostat mimics an environment where cells can assemble as highly reproducible spheroids with low shear forces and active nutrient diffusion. We demonstrate that both cancer and non-cancer hepatocytes (HepG2/C3A and THLE-3 cell lines) require 3 weeks of growth prior to achieving functionalities comparable to liver cells. This protocol highlights the convenience of utilizing incubators for 3D cells with cameras monitoring the cell growth, as snapshots can be taken to count and measure spheroids upon treatment. We describe the comparison of THLE-3 and HepG2/C3A cell lines, showing how non-cancerous cell lines can be grown as well as immortalized cancer cells. We demonstrate and illustrate how proteomics experiments can be conducted from a few spheroids, which can be collected without perturbing cell signaling, i.e., no trypsinization required. We show that proteomics analysis can be used to monitor the typical liver phenotype of respiratory chain metabolism and the production of proteins involved in metal detoxification and describe a semi-automated system to count and measure the spheroid's area. Altogether, the protocol presents a toolbox that comprises a phenotypic characterization via image capture and a proteomics pipeline to experiment on 3D cell culture models.
Topics: Cell Culture Techniques, Three Dimensional; Cell Cycle; Cell Line; Cell Proliferation; Diffusion
PubMed: 37607073
DOI: 10.3791/65086 -
Molecules (Basel, Switzerland) Dec 2023By reducing the 2-nitrophenylhydrazone of cyclohexanone with sodium dithionite, an unexpected yellow compound was obtained instead of the corresponding colorless amino... (Review)
Review
By reducing the 2-nitrophenylhydrazone of cyclohexanone with sodium dithionite, an unexpected yellow compound was obtained instead of the corresponding colorless amino derivative. Many years later, the structure of this compound, namely, cyclohexane-3-spiro-3,4-dihydro-1,2,4-benzotriazine, was demonstrated. From that time, the reduction of 2-nitrophenylhydrazones of different kinds of ketones, followed by air oxidation of the initially formed amino compounds, has represented a general way to synthesize a variety of 3,3-disubstituted 3,4-dihydro-1,2,4-benzotriazines. Many derivatives have been obtained so far by a single research group, and most of them have demonstrated interesting pharmacological activities, mainly antihypertensive, anti-inflammatory, and diuretic effects and other activities with lower diffusion. Moreover, 3,3-disubstituted 3,4-dihydro-1,2,4-benzotriazines represent a novel class of ligands for sigma receptors, with nanomolar affinity to the σ subtype. This property might promote the development of agents for cardiovascular, neurodegenerative, and proliferative pathologies. The present commentary, by collecting compounds and biological results obtained so far, intends to celebrate the centennial of the discovery of the first member of this class of compounds and to promote further investigation in the field.
Topics: Receptors, sigma; Antihypertensive Agents; Diffusion; Ketones; Triazines
PubMed: 38202715
DOI: 10.3390/molecules29010132