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Nature Communications Aug 2023Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate...
Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium. Furthermore, in turning cells, both lamellipodium structure and intracellular diffusion dynamics are also changed, with left-right symmetry breaking. We propose a mechanism involving the front-localized actin polymerization and increased molecular crowding in the lamellipodium to explain how cells spatiotemporally coordinate the intracellular diffusion dynamics and the lamellipodium structure in regulating their migrations.
Topics: Animals; Cell Movement; Diffusion; Erythrocytes, Abnormal; Pseudopodia
PubMed: 37620390
DOI: 10.1038/s41467-023-40858-x -
Toxins Sep 2023Blue-green algae, or cyanobacteria, may be prevalent in our rivers and tap water. These minuscule bacteria can grow swiftly and form blooms in warm, nutrient-rich water.... (Review)
Review
Blue-green algae, or cyanobacteria, may be prevalent in our rivers and tap water. These minuscule bacteria can grow swiftly and form blooms in warm, nutrient-rich water. Toxins produced by cyanobacteria can pollute rivers and streams and harm the liver and nervous system in humans. This review highlights the properties of 25 toxin types produced by 12 different cyanobacteria genera. The review also covered strategies for reducing and controlling cyanobacteria issues. These include using physical or chemical treatments, cutting back on fertilizer input, algal lawn scrubbers, and antagonistic microorganisms for biocontrol. Micro-, nano- and ultrafiltration techniques could be used for the removal of internal and extracellular cyanotoxins, in addition to powdered or granular activated carbon, ozonation, sedimentation, ultraviolet radiation, potassium permanganate, free chlorine, and pre-treatment oxidation techniques. The efficiency of treatment techniques for removing intracellular and extracellular cyanotoxins is also demonstrated. These approaches aim to lessen the risks of cyanobacterial blooms and associated toxins. Effective management of cyanobacteria in water systems depends on early detection and quick action. Cyanobacteria cells and their toxins can be detected using microscopy, molecular methods, chromatography, and spectroscopy. Understanding the causes of blooms and the many ways for their detection and elimination will help the management of this crucial environmental issue.
Topics: Humans; Drinking Water; Lakes; Ultraviolet Rays; Diffusion; Cyanobacteria Toxins
PubMed: 37756009
DOI: 10.3390/toxins15090582 -
European Radiology Sep 2023This study aimed to evaluate the effect of achievable t on the accuracy of microstructural mapping based on simulation and patient experiments, and investigate the...
OBJECTIVES
This study aimed to evaluate the effect of achievable t on the accuracy of microstructural mapping based on simulation and patient experiments, and investigate the feasibility of t-dMRI in distinguishing prognostic factors in breast cancer patients.
METHODS
Simulation was performed using different t settings. Patients with breast cancer were enrolled prospectively between November 2020 and January 2021, who underwent oscillating and pulsed gradient encoded dMRI on a 3-T scanner using short-/long-t protocol with oscillating frequency up to 50/33 Hz. Data were fitted with a two-compartment model to estimate cell diameter (d), intracellular fraction (f), and diffusivities. Estimated microstructural markers were used to differentiate immunohistochemical receptor status and the presence of lymph node (LN), which were correlated with histopathological measurements.
RESULTS
Simulation results showed that d fitted from the short-t protocol significantly reduced estimation error than those from long-t (2.07 ± 1.51% versus 3.05 ± 1.92%, p < 0.0001) while the estimation error of f was robust to different protocols. Among a total of 37 breast cancer patients, the estimated d was significantly higher in HER2-positive and LN-positive (p < 0.05) groups compared to their negative counterparts only using the short-t protocol. Histopathological validation in a subset of 6 patients with whole slide images showed the estimated d was highly correlated with measurements from H&E staining (r = 0.84, p = 0.03) only using the short-t protocol.
CONCLUSIONS
The results indicated the necessity of short-t for accurate microstructural mapping in breast cancer. The current t-dMRI with a total acquisition time of 4.5 min showed its potential in the diagnosis of breast cancer.
KEY POINTS
• Short t is important for accurate microstructural mapping in breast cancer using the t-dMRI technique, based on simulation and histological validation. • The 4.5-min t-dMRI protocol showed potential clinical value for breast cancer, given the difference in cell diameter between HER2/LN positive and negative groups.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Computer Simulation; Diffusion Magnetic Resonance Imaging; Diffusion
PubMed: 37071169
DOI: 10.1007/s00330-023-09623-y -
European Spine Journal : Official... May 2024The intervertebral disc being avascular depends on diffusion and load-based convection for essential nutrient supply and waste removal. There are no reliable methods to...
ISSLS prize in clinical/bioengineering science 2024: How standing and supine positions influence nutrient transport in human lumbar discs?-A serial post-contrast MRI study evaluating interplay between convection and diffusion.
PURPOSE
The intervertebral disc being avascular depends on diffusion and load-based convection for essential nutrient supply and waste removal. There are no reliable methods to simultaneously investigate them in humans under natural loads. For the first time, present study aims to investigate this by strategically employing positional MRI and post-contrast studies in three physiological positions: supine, standing and post-standing recovery.
METHODS
A total of 100 healthy intervertebral discs from 20 volunteers were subjected to a serial post-contrast MR study after injecting 0.3 mmol/kg gadodiamide and T1-weighted MR images were obtained at 0, 2, 6, 12 and 24 h. At each time interval, images were obtained in three positions, i.e. supine, standing and post-standing recovery supine. The signal intensity values at endplate zone and nucleus pulposus were measured. Enhancement percentages were calculated and analysed comparing three positions.
RESULTS
During unloaded supine position, there was slow gradual increase in enhancement reaching peak at 6 h. When the subjects assumed standing position, there was immediate loss of enhancement at nucleus pulposus which resulted in reciprocal increase in enhancement at endplate zone (washout phenomenon). Interestingly, when subjects assumed the post-standing recovery position, the nucleus pulposus regained the enhancement and endplate zone showed reciprocal loss (pumping-in phenomenon).
CONCLUSIONS
For the first time, present study documented acute effects of physiological loading and unloading on nutrition of human discs in vivo. While during rest, solutes diffused gradually into disc, the diurnal short loading and unloading redistribute small solutes by convection. Standing caused rapid solute depletion but promptly regained by assuming resting supine position.
Topics: Humans; Intervertebral Disc; Adult; Male; Magnetic Resonance Imaging; Lumbar Vertebrae; Female; Supine Position; Standing Position; Diffusion; Convection; Young Adult; Contrast Media; Gadolinium DTPA; Nutrients
PubMed: 38662214
DOI: 10.1007/s00586-024-08243-4 -
Neurology Jan 2024There is currently no validated disease-stage biomarker for amyotrophic lateral sclerosis (ALS). The identification of quantitative and reproducible markers of disease... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
There is currently no validated disease-stage biomarker for amyotrophic lateral sclerosis (ALS). The identification of quantitative and reproducible markers of disease stratification in ALS is fundamental for study design definition and inclusion of homogenous patient cohorts into clinical trials. Our aim was to assess the rearrangements of structural and functional brain connectivity underlying the clinical stages of ALS, to suggest objective, reproducible measures provided by MRI connectomics mirroring disease staging.
METHODS
In this observational study, patients with ALS and healthy controls (HCs) underwent clinical evaluation and brain MRI on a 3T scanner. Patients were classified into 4 groups, according to the King's staging system. Structural and functional brain connectivity matrices were obtained using diffusion tensor and resting-state fMRI data, respectively. Whole-brain network-based statistics (NBS) analysis and comparisons of intraregional and inter-regional connectivity values using analysis of covariance models were performed between groups. Correlations between MRI and clinical/cognitive measures were tested using Pearson coefficient.
RESULTS
One hundred four patients with ALS and 61 age-matched and sex-matched HCs were included. NBS and regional connectivity analyses demonstrated a progressive decrease of intranetwork and internetwork structural connectivity of sensorimotor regions at increasing ALS stages in our cohort, compared with HCs. By contrast, functional connectivity showed divergent patterns between King's stages 3 (increase in basal ganglia and temporal circuits [ = 0.04 and = 0.05, respectively]) and 4 (frontotemporal decrease [ = 0.03]), suggesting a complex interplay between opposite phenomena in late stages of the disease. Intraregional sensorimotor structural connectivity was correlated with ALS Functional Rating Scale-revised (ALSFRS-r) score ( = 0.31, < 0.001) and upper motor neuron burden ( = -0.25, = 0.01). Inter-regional frontal-sensorimotor structural connectivity was also correlated with ALSFRS-r ( = 0.24, = 0.02). No correlations with cognitive measures were found.
DISCUSSION
MRI of the brain allows to demonstrate and quantify increasing disruption of structural connectivity involving the sensorimotor networks in ALS, mirroring disease stages. Frontotemporal functional disconnection seems to characterize only advanced disease phases. Our findings support the utility of MRI connectomics to stratify patients and stage brain pathology in ALS in a reproducible way, which may mirror clinical progression.
Topics: Humans; Amyotrophic Lateral Sclerosis; Basal Ganglia; Brain; Diffusion; Motor Neurons; Male; Female
PubMed: 38165325
DOI: 10.1212/WNL.0000000000207946 -
Nucleic Acids Research Jul 2023Target search models of DNA-binding proteins in cells typically consider search mechanisms that include 3D diffusion and 1D sliding, which can be characterized by...
Target search models of DNA-binding proteins in cells typically consider search mechanisms that include 3D diffusion and 1D sliding, which can be characterized by single-molecule tracking on DNA. However, the finding of liquid droplets of DNA and nuclear components in cells cast doubt on extrapolation from the behavior in ideal non-condensed DNA conditions to those in cells. In this study, we investigate the target search behavior of DNA-binding proteins in reconstituted DNA-condensed droplets using single-molecule fluorescence microscopy. To mimic nuclear condensates, we reconstituted DNA-condensed droplets using dextran and PEG polymers. In the DNA-condensed droplets, we measured the translational movement of four DNA-binding proteins (p53, Nhp6A, Fis and Cas9) and p53 mutants possessing different structures, sizes, and oligomeric states. Our results demonstrate the presence of fast and slow mobility modes in DNA-condensed droplets for the four DNA-binding proteins. The slow mobility mode capability is correlated strongly to the molecular size and the number of DNA-binding domains on DNA-binding proteins, but only moderately to the affinity to single DNA segments in non-condensed conditions. The slow mobility mode in DNA-condensed droplets is interpreted as a multivalent interaction mode of the DNA-binding protein to multiple DNA segments.
Topics: DNA-Binding Proteins; Tumor Suppressor Protein p53; DNA; Protein Domains; Diffusion
PubMed: 37283050
DOI: 10.1093/nar/gkad471 -
Journal of Mathematical Biology Apr 2024Cell-cell adhesion plays a vital role in the development and maintenance of multicellular organisms. One of its functions is regulation of cell migration, such as...
Cell-cell adhesion plays a vital role in the development and maintenance of multicellular organisms. One of its functions is regulation of cell migration, such as occurs, e.g. during embryogenesis or in cancer. In this work, we develop a versatile multiscale approach to modelling a moving self-adhesive cell population that combines a careful microscopic description of a deterministic adhesion-driven motion component with an efficient mesoscopic representation of a stochastic velocity-jump process. This approach gives rise to mesoscopic models in the form of kinetic transport equations featuring multiple non-localities. Subsequent parabolic and hyperbolic scalings produce general classes of equations with non-local adhesion and myopic diffusion, a special case being the classical macroscopic model proposed in Armstrong et al. (J Theoret Biol 243(1): 98-113, 2006). Our simulations show how the combination of the two motion effects can unfold. Cell-cell adhesion relies on the subcellular cell adhesion molecule binding. Our approach lends itself conveniently to capturing this microscopic effect. On the macroscale, this results in an additional non-linear integral equation of a novel type that is coupled to the cell density equation.
Topics: Cell Adhesion; Cell Movement; Diffusion; Embryonic Development; Kinetics
PubMed: 38568280
DOI: 10.1007/s00285-024-02079-8 -
Physica Medica : PM : An International... Mar 2024Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new...
PURPOSE
Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new synthetically generated datapoints, using generative models, such as Denoising Diffusion Probabilistic Models (DDPM). In this study, we implemented DDPM to improve performance of a tumor local control model, trained on imbalanced dataset, and compare this approach with other common techniques.
METHODS
A dataset of 535 NSCLC patients treated with SBRT (50 Gy/5 fractions) was used to train a deep learning outcome model for tumor local control prediction. The dataset included complete treatment planning data (planning CT images, 3D planning dose distribution and patient demographics) with sparsely distributed endpoints (6-7 % experiencing local failure). Consequently, we trained a novel conditional 3D DDPM model to generate synthetic treatment planning data. Synthetically generated treatment planning datapoints were used to supplement the real training dataset and the improvement in the model's performance was studied. Obtained results were also compared to other common techniques for class imbalanced training, such as Oversampling, Undersampling, Augmentation, Class Weights, SMOTE and ADASYN.
RESULTS
Synthetic DDPM-generated data were visually trustworthy, with Fréchet inception distance (FID) below 50. Extending the training dataset with the synthetic data improved the model's performance by more than 10%, while other techniques exhibited only about 4% improvement.
CONCLUSIONS
DDPM introduces a novel approach to class-imbalanced outcome modelling problems. The model generates realistic synthetic radiotherapy planning data, with a strong potential to increase performance and robustness of outcome models.
Topics: Humans; Bisacodyl; Carcinoma, Non-Small-Cell Lung; Diffusion; Lung Neoplasms
PubMed: 38325221
DOI: 10.1016/j.ejmp.2024.103307 -
Journal of Visualized Experiments : JoVE Mar 2024Two-photon microscopy has emerged as a potent tool for evaluating deep tissue cells and characterizing the alignment of the extracellular matrix (ECM) in various...
Two-photon microscopy has emerged as a potent tool for evaluating deep tissue cells and characterizing the alignment of the extracellular matrix (ECM) in various biological systems. This technique relies on nonlinear light-matter interactions to detect two distinct signals: the second harmonic generated (SHG) diffusion signal, which facilitates the visualization of collagen fibers and their orientation, and the near-infrared excitation signal for imaging ultraviolet excited autofluorescence. SHG imaging proves especially effective in visualizing collagen fibers due to the non-centrosymmetric crystalline structure of fibrillar collagen I. Given that tendons are matrix-rich tissues with a limited number of cells, their high collagen content makes them ideal candidates for analysis using two-photon microscopy. Consequently, two-photon microscopy offers a valuable means to analyze and characterize collagen abnormalities in tendons. Its application extends to studying tendon development, injuries, healing, and aging, enabling the comprehensive characterization of tendon cells and their interactions with the ECM under various conditions using two-photon microscopy tools. This protocol outlines the use of two-photon microscopy in tendon biology and presents an adapted methodology to achieve effective imaging and characterization of tendon cells during development and after injury. The method allows the utilization of thin microscopic sections to create a comprehensive image of the ECM within tendons and the cells that interact with this matrix. Most notably, the article showcases a technique to generate 3D images using two-photon microscopy in animal models.
Topics: Animals; Microscopy; Aging; Diffusion; Tendons; Collagen
PubMed: 38619235
DOI: 10.3791/65853 -
Bulletin of Mathematical Biology Dec 2023We propose a two stages mosquito egg-larvae model with seasonality as a simplification of a four stages one. For the simplified model we characterize the dynamics in...
We propose a two stages mosquito egg-larvae model with seasonality as a simplification of a four stages one. For the simplified model we characterize the dynamics in terms of the vectorial reproduction number, [Formula: see text], obtaining extinction if [Formula: see text] and convergence to a unique positive periodic orbit if [Formula: see text]. We illustrate each case with an example, by providing general conditions on the periodic coefficients for its occurrence. These examples are further developed using numerical simulations where the periodic parameters satisfy the conditions obtained. In the [Formula: see text] case, real climatic data is used for inferring the parameter behaviour. For the four stage system, using alternative oviposition rate functions, we present a result which generalizes others given for models with delays and even with diffusion to the case in which competition between the larvae is introduced. The analytical study of our initial four stages system when [Formula: see text] remains open, since we were not able to prove that in this case the system is dissipative.
Topics: Animals; Female; Mathematical Concepts; Models, Biological; Culicidae; Diffusion; Larva
PubMed: 38108949
DOI: 10.1007/s11538-023-01238-0