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Physical Review. E Mar 2021Several recent experiments, including our own experiments in the fission yeast, Schizosaccharomyces pombe, have characterized the motions of gene loci within living...
Several recent experiments, including our own experiments in the fission yeast, Schizosaccharomyces pombe, have characterized the motions of gene loci within living nuclei by measuring the locus position over time, then proceeding to obtain the statistical properties of this motion. To address the question of whether a population of such single-particle tracks, obtained from many different cells, corresponds to a single mode of diffusion, we derive theoretical equations describing the probability distribution of the displacement covariance, assuming the displacement itself is a zero-mean multivariate Gaussian random variable. We also determine the corresponding theoretical means, variances, and third central moments. Bolstering the theory is good agreement between its predictions and the results obtained for various simulated and measured data sets, including simulated particle trajectories undergoing simple and anomalous diffusion, and the measured trajectories of an optically trapped bead in water, and in a viscoelastic polymer solution. We also show that, for sufficiently long tracks, each covariance distribution in all of these examples is well-described by a skew-normal distribution with mean, variance, and skewness given by the theory. However, for the experimentally measured motion of a gene locus in S. pombe, we find that the first two covariance distributions are wider than predicted, although the third and subsequent covariance distributions are well-described by theory. This observation suggests that the origin of the theory-experiment discrepancy in this case is associated with localization noise, which influences only the first two covariances. Thus, we hypothesized that the discrepancy is caused by locus-to-locus heterogeneity in the localization noise, of independent measurements of the same tagged site. Indeed, simulations implementing heterogeneous localization noise revealed that the excess covariance widths can be largely recreated on the basis of heterogeneous noise. Thus, we conclude that the motion of gene loci in fission yeast is consistent with a single mode of diffusion.
Topics: Diffusion; Motion; Single Molecule Imaging
PubMed: 33862686
DOI: 10.1103/PhysRevE.103.032405 -
Magnetic Resonance in Medicine Dec 2021Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article... (Review)
Review
Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article reviews an emerging paradigm that has the potential to provide a more detailed assessment of tissue microstructure-combined diffusion-relaxometry imaging. Combined diffusion-relaxometry acquisitions vary multiple MR contrast encodings-such as b-value, gradient direction, inversion time, and echo time-in a multidimensional acquisition space. When paired with suitable analysis techniques, this enables quantification of correlations and coupling between multiple MR parameters-such as diffusivity, , , and . This opens the possibility of disentangling multiple tissue compartments (within voxels) that are indistinguishable with single-contrast scans, enabling a new generation of microstructural maps with improved biological sensitivity and specificity.
Topics: Brain; Diffusion; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging; Models, Theoretical
PubMed: 34411331
DOI: 10.1002/mrm.28963 -
Environmental Science and Pollution... Jul 2022This work comprehensively reviews the equations governing multicomponent flow and reactive transport in porous media on the pore-scale, mesoscale and continuum scale.... (Review)
Review
This work comprehensively reviews the equations governing multicomponent flow and reactive transport in porous media on the pore-scale, mesoscale and continuum scale. For each of these approaches, the different numerical schemes for solving the coupled advection-diffusion-reactions equations are presented. The parameters influenced by coupled biological and chemical reactions in evolving porous media are emphasised and defined from a pore-scale perspective. Recent pore-scale studies, which have enhanced the basic understanding of processes that affect and control porous media parameters, are discussed. Subsequently, a summary of the common methods used to describe the transport process, fluid flow, reactive surface area and reaction parameters such as porosity, permeability and tortuosity are reviewed.
Topics: Diffusion; Models, Theoretical; Porosity
PubMed: 35522402
DOI: 10.1007/s11356-022-20466-w -
Bioinformatics (Oxford, England) Sep 2023As an important player in transcriptome regulation, microRNAs may effectively diffuse somatic mutation impacts to broad cellular processes and ultimately manifest...
MOTIVATION
As an important player in transcriptome regulation, microRNAs may effectively diffuse somatic mutation impacts to broad cellular processes and ultimately manifest disease and dictate prognosis. Previous studies that tried to correlate mutation with gene expression dysregulation neglected to adjust for the disparate multitudes of false positives associated with unequal sample sizes and uneven class balancing scenarios.
RESULTS
To properly address this issue, we developed a statistical framework to rigorously assess the extent of mutation impact on microRNAs in relation to a permutation-based null distribution of a matching sample structure. Carrying out the framework in a pan-cancer study, we ascertained 9008 protein-coding genes with statistically significant mutation impacts on miRNAs. Of these, the collective miRNA expression for 83 genes showed significant prognostic power in nine cancer types. For example, in lower-grade glioma, 10 genes' mutations broadly impacted miRNAs, all of which showed prognostic value with the corresponding miRNA expression. Our framework was further validated with functional analysis and augmented with rich features including the ability to analyze miRNA isoforms; aggregative prognostic analysis; advanced annotations such as mutation type, regulator alteration, somatic motif, and disease association; and instructive visualization such as mutation OncoPrint, Ideogram, and interactive mRNA-miRNA network.
AVAILABILITY AND IMPLEMENTATION
The data underlying this article are available in MutMix, at http://innovebioinfo.com/Database/TmiEx/MutMix.php.
Topics: Humans; Diffusion; Glioma; MicroRNAs; Mutation; RNA, Messenger
PubMed: 37624931
DOI: 10.1093/bioinformatics/btad520 -
ACS Nano Nov 2020Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver...
Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver cells. A variety of nonliving artificial cell models have been developed in recent years that mimic various aspects of diffusion-based intercellular communication. However, localized secretion of diffusive signals from individual protocells, which is critical for mimicking biological sender-receiver systems, has remained challenging to control precisely. Here, we engineer light-responsive, DNA-encoded sender-receiver architectures, where protein-polymer microcapsules act as cell mimics and molecular communication occurs through diffusive DNA signals. We prepare spatial distributions of sender and receiver protocells using a microfluidic trapping array and set up a signaling gradient from a single sender cell using light, which activates surrounding receivers through DNA strand displacement. Our systematic analysis reveals how the effective signal range of a single sender is determined by various factors including the density and permeability of receivers, extracellular signal degradation, signal consumption, and catalytic regeneration. In addition, we construct a three-population configuration where two sender cells are embedded in a dense array of receivers that implement Boolean logic and investigate spatial integration of nonidentical input cues. The results offer a means for studying diffusion-based sender-receiver topologies and present a strategy to achieve the congruence of reaction-diffusion and positional information in chemical communication systems that have the potential to reconstitute collective cellular patterns.
Topics: Artificial Cells; Cell Communication; DNA; Diffusion; Signal Transduction
PubMed: 33078948
DOI: 10.1021/acsnano.0c07537 -
Robust and efficient identification of optimal mixing perturbations using proxy multiscale measures.Philosophical Transactions. Series A,... Jun 2022Understanding and optimizing passive scalar mixing in a diffusive fluid flow at finite Péclet number [Formula: see text] (where [Formula: see text] and [Formula: see...
Understanding and optimizing passive scalar mixing in a diffusive fluid flow at finite Péclet number [Formula: see text] (where [Formula: see text] and [Formula: see text] are characteristic velocity and length scales, and [Formula: see text] is the molecular diffusivisity of the scalar) is a fundamental problem of interest in many environmental and industrial flows. Particularly when [Formula: see text], identifying initial perturbations of given energy that optimally and thoroughly mix fluids of initially different properties can be computationally challenging. To address this challenge, we consider the identification of initial perturbations in an idealized two-dimensional flow on a torus that extremize various measures over finite time horizons. We identify such 'optimal' initial perturbations using the 'direct-adjoint looping' method, thus requiring the evolving flow to satisfy the governing equations and boundary conditions at all points in space and time. We demonstrate that minimizing multiscale measures commonly known as 'mix-norms' over short time horizons is a computationally efficient and robust way to identify initial perturbations that thoroughly mix layered scalar distributions over relatively long time horizons, provided the magnitude of the mix-norm's index is not too large. Minimization of such mix-norms triggers the development of coherent vortical flow structures which effectively mix, with the particular properties of these flow structures depending on [Formula: see text] and also the time horizon of interest. This article is part of the theme issue 'Mathematical problems in physical fluid dynamics (part 1)'.
Topics: Diffusion; Hydrodynamics
PubMed: 35465721
DOI: 10.1098/rsta.2021.0026 -
The Journal of General Physiology Apr 2021Spines are tiny nanoscale protrusions from dendrites of neurons. In the cortex and hippocampus, most of the excitatory postsynaptic sites reside in spines. The bulbous... (Review)
Review
Spines are tiny nanoscale protrusions from dendrites of neurons. In the cortex and hippocampus, most of the excitatory postsynaptic sites reside in spines. The bulbous spine head is connected to the dendritic shaft by a thin membranous neck. Because the neck is narrow, spine heads are thought to function as biochemically independent signaling compartments. Thus, dynamic changes in the composition, distribution, mobility, conformations, and signaling properties of molecules contained within spines can account for much of the molecular basis of postsynaptic function and regulation. A major factor in controlling these changes is the diffusional properties of proteins within this small compartment. Advances in measurement techniques using fluorescence microscopy now make it possible to measure molecular diffusion within single dendritic spines directly. Here, we review the regulatory mechanisms of diffusion in spines by local intra-spine architecture and discuss their implications for neuronal signaling and synaptic plasticity.
Topics: Dendritic Spines; Diffusion; Hippocampus; Neuronal Plasticity; Neurons; Synapses
PubMed: 33720306
DOI: 10.1085/jgp.202012814 -
Magnetic Resonance in Medicine Jun 2023To quantify the variations of the power-law dependences on diffusion time t or gradient frequency of extracellular water diffusion measured by diffusion MRI (dMRI).
PURPOSE
To quantify the variations of the power-law dependences on diffusion time t or gradient frequency of extracellular water diffusion measured by diffusion MRI (dMRI).
METHODS
Model cellular systems containing only extracellular water were used to investigate the dependence of , the extracellular diffusion coefficient. Computer simulations used a randomly packed tissue model with realistic intracellular volume fractions and cell sizes. DMRI measurements were performed on samples consisting of liposomes containing heavy water(D O, deuterium oxide) dispersed in regular water (H O). was obtained over a broad range (∼1-1000 ms) and then fit power-law equations and .
RESULTS
Both simulated and experimental results suggest that no single power-law adequately describes the behavior of over the range of diffusion times of most interest in practical dMRI. Previous theoretical predictions are accurate over only limited ranges; for example, is valid only for short times, whereas or is valid only for long times but cannot describe other ranges simultaneously. For the specific range of 5-70 ms used in typical human dMRI measurements, matches the data well empirically.
CONCLUSION
The optimal power-law fit of extracellular diffusion varies with diffusion time. The dependency obtained at short or long limits cannot be applied to typical dMRI measurements in human cancer or liver. It is essential to determine the appropriate diffusion time range when modeling extracellular diffusion in dMRI-based quantitative microstructural imaging.
Topics: Humans; Diffusion Magnetic Resonance Imaging; Neoplasms; Diffusion; Models, Biological; Computer Simulation
PubMed: 36740894
DOI: 10.1002/mrm.29594 -
Advanced Science (Weinheim,... Aug 2022Ion transport under nanoconfined spaces is a ubiquitous phenomenon in nature and plays an important role in the energy conversion and signal transduction processes of... (Review)
Review
Ion transport under nanoconfined spaces is a ubiquitous phenomenon in nature and plays an important role in the energy conversion and signal transduction processes of both biological and artificial systems. Unlike the free diffusion in continuum media, anomalous behaviors of ions are often observed in nanostructured systems, which is governed by the complex interplay between various interfacial interactions. Conventionally, nanoionics mainly refers to the study of ion transport in solid-state nanosystems. In this review, to extent this concept is proposed and a new framework to understand the phenomena, mechanism, methodology, and application associated with ion transport at the nanoscale is put forward. Specifically, here nanoionics is summarized into three categories, i.e., biological, artificial, and hybrid, and discussed the characteristics of each system. Compared with nanoelectronics, nanoionics is an emerging research field with many theoretical and practical challenges. With this forward-looking perspective, it is hoped that nanoionics can attract increasing attention and find wide range of applications as nanoelectronics.
Topics: Diffusion; Ion Transport; Ions; Nanostructures
PubMed: 35723422
DOI: 10.1002/advs.202200534 -
Fluids and Barriers of the CNS Mar 2023Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of...
BACKGROUND
Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of the brain parenchyma. Detailed fluid mechanical models of diffusive and advective transport in the brain are promising tools to investigate theories of transport.
METHODS
We derive theoretical estimates of astrocyte endfoot sheath permeability for advective and diffusive transport and its variation in microvascular networks from mouse brain cortex. The networks are based on recently published experimental data and generated endfoot patterns are based on Voronoi tessellations of the perivascular surface. We estimate corrections for projection errors in previously published data.
RESULTS
We provide structural-functional relationships between vessel radius and resistance that can be directly used in flow and transport simulations. We estimate endfoot sheath filtration coefficients in the range [Formula: see text] to [Formula: see text], diffusion membrane coefficients for small solutes in the range [Formula: see text] to [Formula: see text], and gap area fractions in the range 0.2-0.6%, based on a inter-endfoot gap width of 20 nm.
CONCLUSIONS
The astrocyte endfoot sheath surrounding microvessels forms a secondary barrier to extra-cellular transport, separating the extra-cellular space of the parenchyma and the perivascular space outside the endothelial layer. The filtration and membrane diffusion coefficients of the endfoot sheath are estimated to be an order of magnitude lower than those of the extra-cellular matrix while being two orders of magnitude higher than those of the vessel wall.
Topics: Mice; Animals; Astrocytes; Brain; Biological Transport; Diffusion; Extracellular Space
PubMed: 36941607
DOI: 10.1186/s12987-023-00421-8