-
International Journal of Environmental... Aug 2023The Achilles tendon is the thickest and strongest tendon of the human body, and it is frequently injured during sports activity. The incidence of Achilles tendon... (Review)
Review
The Achilles tendon is the thickest and strongest tendon of the human body, and it is frequently injured during sports activity. The incidence of Achilles tendon pathologies has increased over recent decades, especially in the last few years, because of increased sports participation among the general population and due to the diffusion of competitive sports at a high level. Tendinopathies are common in athletes and in middle-aged overweight patients. The term "tendinopathy" refers to a condition characterised clinically by pain and swelling, with functional limitations of tendon and nearby structures, and consequently to chronic failure of healing response process. Tendinopathies can produce marked morbidity, and at present, scientifically validated management modalities are limited. Despite the constantly increasing interest and number of studies about Achilles tendinopathy (AT), there is still not a consensual point of view on which is the best treatment, and its management is still controversial. AT can be treated conservatively primarily, with acceptable results and clinical outcomes. When this approach fails, surgery should be considered. Several surgical procedures have been described for both conditions with a relatively high rate of success with few complications and the decision for treatment in patients with AT should be tailored on patient's needs and level of activity. The aim of this article is to give insights about the pathogenesis and most used and recent treatment options for AT.
Topics: Middle Aged; Humans; Achilles Tendon; Tendinopathy; Athletes; Diffusion; Musculoskeletal Diseases
PubMed: 37681821
DOI: 10.3390/ijerph20176681 -
Science Advances Aug 2023Lipid synthesis is necessary for formation of epithelial barriers and homeostasis with external microbes. An analysis of the response of human keratinocytes to several...
Lipid synthesis is necessary for formation of epithelial barriers and homeostasis with external microbes. An analysis of the response of human keratinocytes to several different commensal bacteria on the skin revealed that induced a large increase in essential lipids including triglycerides, ceramides, cholesterol, and free fatty acids. A similar response occurred in mouse epidermis and in human skin affected with acne. Further analysis showed that this increase in lipids was mediated by short-chain fatty acids produced by and was dependent on increased expression of several lipid synthesis genes including . Inhibition or RNA silencing of peroxisome proliferator-activated receptor-α (PPARα), but not PPARβ and PPARγ, blocked this response. The increase in keratinocyte lipid content improved innate barrier functions including antimicrobial activity, paracellular diffusion, and transepidermal water loss. These results reveal that metabolites from a common commensal bacterium have a previously unappreciated influence on the composition of epidermal lipids.
Topics: Humans; Animals; Mice; Epidermis; Skin; Keratinocytes; Ceramides; Diffusion
PubMed: 37595033
DOI: 10.1126/sciadv.adg6262 -
Nature Sep 2023Transient receptor potential (TRP) channels are a large, eukaryotic ion channel superfamily that control diverse physiological functions, and therefore are attractive...
Transient receptor potential (TRP) channels are a large, eukaryotic ion channel superfamily that control diverse physiological functions, and therefore are attractive drug targets. More than 210 structures from more than 20 different TRP channels have been determined, and all are tetramers. Despite this wealth of structures, many aspects concerning TRPV channels remain poorly understood, including the pore-dilation phenomenon, whereby prolonged activation leads to increased conductance, permeability to large ions and loss of rectification. Here, we used high-speed atomic force microscopy (HS-AFM) to analyse membrane-embedded TRPV3 at the single-molecule level and discovered a pentameric state. HS-AFM dynamic imaging revealed transience and reversibility of the pentamer in dynamic equilibrium with the canonical tetramer through membrane diffusive protomer exchange. The pentamer population increased upon diphenylboronic anhydride (DPBA) addition, an agonist that has been shown to induce TRPV3 pore dilation. On the basis of these findings, we designed a protein production and data analysis pipeline that resulted in a cryogenic-electron microscopy structure of the TRPV3 pentamer, showing an enlarged pore compared to the tetramer. The slow kinetics to enter and exit the pentameric state, the increased pentamer formation upon DPBA addition and the enlarged pore indicate that the pentamer represents the structural correlate of pore dilation. We thus show membrane diffusive protomer exchange as an additional mechanism for structural changes and conformational variability. Overall, we provide structural evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.
Topics: Anhydrides; Data Analysis; Diffusion; Protein Subunits; TRPV Cation Channels; Microscopy, Atomic Force; Molecular Targeted Therapy; Cryoelectron Microscopy; Protein Structure, Quaternary; Protein Multimerization
PubMed: 37648856
DOI: 10.1038/s41586-023-06470-1 -
A dirigent protein complex directs lignin polymerization and assembly of the root diffusion barrier.Science (New York, N.Y.) Oct 2023Functionally similar to the tight junctions present in animal guts, plant roots have evolved a lignified Casparian strip as an extracellular diffusion barrier in the...
Functionally similar to the tight junctions present in animal guts, plant roots have evolved a lignified Casparian strip as an extracellular diffusion barrier in the endodermis to seal the root apoplast and maintain nutrient homeostasis. How this diffusion barrier is structured has been partially defined, but its lignin polymerization and assembly steps remain elusive. Here, we characterize a family of dirigent proteins (DPs) essential for both the localized polymerization of lignin required for Casparian strip biogenesis in the cell wall and for attachment of the strip to the plasma membrane to seal the apoplast. We reveal a Casparian strip lignification mechanism that requires cooperation between DPs and the Schengen pathway. Furthermore, we demonstrate that DPs directly mediate lignin polymerization as part of this mechanism.
Topics: Arabidopsis; Cell Wall; Diffusion; Lignin; Plant Roots; Polymerization; Arabidopsis Proteins
PubMed: 37883539
DOI: 10.1126/science.adi5032 -
Blood Feb 2024
Topics: Humans; Diffusion; Oxygen; Kidney
PubMed: 38386428
DOI: 10.1182/blood.2023023201 -
Biophysical Journal Jun 2024Diffusion determines the turnover of biomolecules in liquid-liquid phase-separated condensates. We considered the mean square displacement and thus the diffusion...
Diffusion determines the turnover of biomolecules in liquid-liquid phase-separated condensates. We considered the mean square displacement and thus the diffusion constant for simple model systems of peptides GGGGG, GGQGG, and GGVGG in aqueous solutions after phase separation by simulating atomic-level models. These solutions readily separate into aqueous and peptide-rich droplet phases. We noted the effect of the peptides being in a solvated, surface, or droplet state on the peptide's diffusion coefficients. Both sequence and peptide conformational distribution were found to influence diffusion and condensate turnover in these systems, with sequence dominating the magnitude of the differences. We found that the most compact structures for each sequence diffused the fastest in the peptide-rich condensate phase. This model result may have implications for turnover dynamics in signaling systems.
Topics: Diffusion; Peptides; Biomolecular Condensates; Amino Acid Sequence; Water; Models, Molecular; Protein Conformation
PubMed: 38751116
DOI: 10.1016/j.bpj.2024.05.009 -
Scientific Reports Jul 2023Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and...
Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy (FCS) to quantify changes in the local environment by measuring the fluorescence lifetime and the diffusion of the monomeric enhanced green fluorescent protein (eGFP), respectively. Real-time monitoring of eGFP fluorescence lifetime showed that a faster response to environmental changes due to MMC is observed than when measuring the acceptor/donor emission ratio using the MMC-sensitive Förster resonance energy transfer sensor (GimRET). This suggests that eGFP molecular electronic states and/or collision frequency are affected by changes in the immediate surroundings due to MMC without requiring conformational changes as is the case for the GimRET sensor. Furthermore, eGFP diffusion assessed by FCS indicated higher intracellular viscosity due to increased MMC during hyperosmotic stress. Our findings reveal that changes in eGFP fluorescence lifetime and diffusion are early indicators of elevated intracellular MMC. Our approach can therefore be used to reveal in live cells short-lived transient states through which MMC builds over time, which could not be observed when measuring changes in other physical properties that occur at slower time scales.
Topics: Diffusion; Electronics; Fluorescence Resonance Energy Transfer; Microscopy, Fluorescence; Protein Aggregates
PubMed: 37481632
DOI: 10.1038/s41598-023-39090-w -
Physical Review Letters Jun 2023Exceptional point (EP) has been captivated as a concept of interpreting eigenvalue degeneracy and eigenstate exchange in non-Hermitian physics. The chirality in the...
Exceptional point (EP) has been captivated as a concept of interpreting eigenvalue degeneracy and eigenstate exchange in non-Hermitian physics. The chirality in the vicinity of EP is intrinsically preserved and usually immune to external bias or perturbation, resulting in the robustness of asymmetric backscattering and directional emission in classical wave fields. Despite recent progress in non-Hermitian thermal diffusion, all state-of-the-art approaches fail to exhibit chiral states or directional robustness in heat transport. Here we report the first discovery of chiral heat transport, which is manifested only in the vicinity of EP but suppressed at the EP of a thermal system. The chiral heat transport demonstrates significant robustness against drastically varying advections and thermal perturbations imposed. Our results reveal the chirality in heat transport process and provide a novel strategy for manipulating mass, charge, and diffusive light.
Topics: Hot Temperature; Diffusion; Physics
PubMed: 37450831
DOI: 10.1103/PhysRevLett.130.266303 -
Proceedings of the National Academy of... Aug 2023Real-world networks are neither regular nor random, a fact elegantly explained by mechanisms such as the Watts-Strogatz or the Barabási-Albert models, among others....
Real-world networks are neither regular nor random, a fact elegantly explained by mechanisms such as the Watts-Strogatz or the Barabási-Albert models, among others. Both mechanisms naturally create shortcuts and hubs, which while enhancing the network's connectivity, also might yield several undesired navigational effects: They tend to be overused during geodesic navigational processes-making the networks fragile-and provide suboptimal routes for diffusive-like navigation. Why, then, networks with complex topologies are ubiquitous? Here, we unveil that these models also entropically generate network bypasses: alternative routes to shortest paths which are topologically longer but easier to navigate. We develop a mathematical theory that elucidates the emergence and consolidation of network bypasses and measure their navigability gain. We apply our theory to a wide range of real-world networks and find that they sustain complexity by different amounts of network bypasses. At the top of this complexity ranking we found the human brain, which points out the importance of these results to understand the plasticity of complex systems.
Topics: Humans; Brain; Diffusion
PubMed: 37490534
DOI: 10.1073/pnas.2305001120 -
Reports on Progress in Physics.... Nov 2023It is well established that a wide variety of phenomena in cellular and molecular biology involve anomalous transport e.g. the statistics for the motility of cells and... (Review)
Review
It is well established that a wide variety of phenomena in cellular and molecular biology involve anomalous transport e.g. the statistics for the motility of cells and molecules are fractional and do not conform to the archetypes of simple diffusion or ballistic transport. Recent research demonstrates that anomalous transport is in many cases heterogeneous in both time and space. Thus single anomalous exponents and single generalised diffusion coefficients are unable to satisfactorily describe many crucial phenomena in cellular and molecular biology. We consider advances in the field of() highlighting: experimental techniques (single molecule methods, microscopy, image analysis, fluorescence correlation spectroscopy, inelastic neutron scattering, and nuclear magnetic resonance), theoretical tools for data analysis (robust statistical methods such as first passage probabilities, survival analysis, different varieties of mean square displacements, etc), analytic theory and generative theoretical models based on simulations. Special emphasis is made on high throughput analysis techniques based on machine learning and neural networks. Furthermore, we consider anomalous transport in the context of microrheology and the heterogeneous viscoelasticity of complex fluids. HAT in the wavefronts of reaction-diffusion systems is also considered since it plays an important role in morphogenesis and signalling. In addition, we present specific examples from cellular biology including embryonic cells, leucocytes, cancer cells, bacterial cells, bacterial biofilms, and eukaryotic microorganisms. Case studies from molecular biology include DNA, membranes, endosomal transport, endoplasmic reticula, mucins, globular proteins, and amyloids.
Topics: Diffusion; Biological Transport; Models, Theoretical; Molecular Biology; Image Processing, Computer-Assisted
PubMed: 37863075
DOI: 10.1088/1361-6633/ad058f