Special Issue "Organization and Function of Cellular Structural Networks"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Organelle Function".

Deadline for manuscript submissions: closed (15 June 2021).

Special Issue Editors

Prof. Dr. Pavel Hozák
E-Mail Website
Guest Editor
Institute of Molecular Genetics AS CR, Laboratory of Biology of the Cell Nucleus & IMG Microscopy Centre, Videnska 1083, 142 20 Prague 4 - Krc, Czech Republic
Interests: cell nucleus; nucleolus; regulation of gene expression; epigenetics; nucleoskeleton; nuclear myosins; actin-related proteins and phospholipids; lamins; laminopathies; phase separation; microscopy
Special Issues and Collections in MDPI journals
Prof. Dr. Elly Hol
E-Mail Website
Guest Editor
University Medical Center Utrecht, Utrecht, The Netherlands
Interests: glia biology of brain diseases; biology of glia and neural stem cells
Prof. Dr. Roy Andrew Quinlan
E-Mail Website
Guest Editor
Department of Biosciences, University of Durham, Upper Mountjoy Science Site, Durham DH1 3LE, UK
Interests: cytoskeleton; intermediate filaments; protein chaperones; small heat shock proteins; the eye lens; aging and cataractogenesis

Special Issue Information

Dear Colleagues,

Structural networks that connect the extracellular matrix and cell surfaces through the cytoskeleton with the nucleoskeleton govern cell, tissue, and organ integrity. Besides their structural roles, these networks participate in a multitude of fundamental functions, e.g., regulating signal- and mechano-transduction, cytoplasmic transport, sequestering biomolecules, maintaining genome organization, and promoting meiosis. Mutations in the building blocks of these networks frequently lead to devastating diseases. The pathogenesis of these diseases is far from being understood and requires a wide interdisciplinary approach that is distinct from the individual research schemes. Based on capacity building measures, coordinated networking and educative activities and interactions with business partners and European research infrastructures, the EuroCellNet COST Action aimed to develop an orchestrated multinational activity grid. This Special Issue collects manuscripts resulting from activities within the Eurocellnet and welcomes original or review contributions related especially to:

- Biophysics of cell and tissue structure;

- Structural analysis of biomolecules involved in mechanobiology;

- New methodologies to study mechanobiology of cells and tissues;

- Mechanobiological principles of rare and common diseases.

Acknowledgement

These articles are based upon work from COST action (CA 15214), supported by COST (European Cooperation in Science and Technology). www.cost.eu

text text

Prof. Dr. Pavel Hozák
Prof. Dr. Elly Hol
Prof. Roy Andrew Quinlan
Guest Editor

Manuscript Submission Information

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Keywords

  • extracellular matrix
  • cytoskeleton
  • nucleoskeleton
  • signal transduction
  • mechano-transduction
  • cellular transport
  • genome organization
  • pathogenesis
  • cell biophysics
  • mechanobiology
  • microscopy
  • structural biology

Published Papers (17 papers)

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Research

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Article
Cystatin C Deficiency Increases LPS-Induced Sepsis and NLRP3 Inflammasome Activation in Mice
Cells 2021, 10(8), 2071; https://doi.org/10.3390/cells10082071 - 12 Aug 2021
Viewed by 380
Abstract
Cystatin C is a potent cysteine protease inhibitor that plays an important role in various biological processes including cancer, cardiovascular diseases and neurodegenerative diseases. However, the role of CstC in inflammation is still unclear. In this study we demonstrated that cystatin C-deficient mice [...] Read more.
Cystatin C is a potent cysteine protease inhibitor that plays an important role in various biological processes including cancer, cardiovascular diseases and neurodegenerative diseases. However, the role of CstC in inflammation is still unclear. In this study we demonstrated that cystatin C-deficient mice were significantly more sensitive to the lethal LPS-induced sepsis. We further showed increased caspase-11 gene expression and enhanced processing of pro-inflammatory cytokines IL-1β and IL-18 in CstC KO bone marrow-derived macrophages (BMDM) upon LPS and ATP stimulation. Pre-treatment of BMDMs with the cysteine cathepsin inhibitor E-64d did not reverse the effect of CstC deficiency on IL-1β processing and secretion, suggesting that the increased cysteine cathepsin activity determined in CstC KO BMDMs is not essential for NLRP3 inflammasome activation. The CstC deficiency had no effect on (mitochondrial) reactive oxygen species (ROS) generation, the MAPK signaling pathway or the secretion of anti-inflammatory cytokine IL-10. However, CstC-deficient BMDMs showed dysfunctional autophagy, as autophagy induction via mTOR and AMPK signaling pathways was suppressed and accumulation of SQSTM1/p62 indicated a reduced autophagic flux. Collectively, our study demonstrates that the excessive inflammatory response to the LPS-induced sepsis in CstC KO mice is dependent on increased caspase-11 expression and impaired autophagy, but is not associated with increased cysteine cathepsin activity. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging
Cells 2021, 10(7), 1755; https://doi.org/10.3390/cells10071755 - 11 Jul 2021
Viewed by 597
Abstract
Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes [...] Read more.
Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
Live Fluorescence Imaging of F-Actin Organization in Chick Whole Embryo Cultures Using SiR-Actin
Cells 2021, 10(7), 1578; https://doi.org/10.3390/cells10071578 - 22 Jun 2021
Viewed by 557
Abstract
Morphogenesis is a continuous process of pattern formation so complex that it requires in vivo monitoring for better understanding. Changes in tissue shape are initiated at the cellular level, where dynamic intracellular F-actin networks determine the shape and motility of cells, influence differentiation [...] Read more.
Morphogenesis is a continuous process of pattern formation so complex that it requires in vivo monitoring for better understanding. Changes in tissue shape are initiated at the cellular level, where dynamic intracellular F-actin networks determine the shape and motility of cells, influence differentiation and cytokinesis and mediate mechanical signaling. Here, we stain F-actin with the fluorogenic probe SiR-actin for live fluorescence imaging of whole chick embryos. We found that 50 nM SiR-actin in the culture medium is a safe and effective concentration for this purpose, as it provides high labeling density without inducing morphological malformations. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
Riluzole Administration to Rats with Levodopa-Induced Dyskinesia Leads to Loss of DNA Methylation in Neuronal Genes
Cells 2021, 10(6), 1442; https://doi.org/10.3390/cells10061442 - 09 Jun 2021
Viewed by 697
Abstract
Dyskinesias are characterized by abnormal repetitive involuntary movements due to dysfunctional neuronal activity. Although levodopa-induced dyskinesia, characterized by tic-like abnormal involuntary movements, has no clinical treatment for Parkinson’s disease patients, animal studies indicate that Riluzole, which interferes with glutamatergic neurotransmission, can improve the [...] Read more.
Dyskinesias are characterized by abnormal repetitive involuntary movements due to dysfunctional neuronal activity. Although levodopa-induced dyskinesia, characterized by tic-like abnormal involuntary movements, has no clinical treatment for Parkinson’s disease patients, animal studies indicate that Riluzole, which interferes with glutamatergic neurotransmission, can improve the phenotype. The rat model of Levodopa-Induced Dyskinesia is a unilateral lesion with 6-hydroxydopamine in the medial forebrain bundle, followed by the repeated administration of levodopa. The molecular pathomechanism of Levodopa-Induced Dyskinesia is still not deciphered; however, the implication of epigenetic mechanisms was suggested. In this study, we investigated the striatum for DNA methylation alterations under chronic levodopa treatment with or without co-treatment with Riluzole. Our data show that the lesioned and contralateral striata have nearly identical DNA methylation profiles. Chronic levodopa and levodopa + Riluzole treatments led to DNA methylation loss, particularly outside of promoters, in gene bodies and CpG poor regions. We observed that several genes involved in the Levodopa-Induced Dyskinesia underwent methylation changes. Furthermore, the Riluzole co-treatment, which improved the phenotype, pinpointed specific methylation targets, with a more than 20% methylation difference relative to levodopa treatment alone. These findings indicate potential new druggable targets for Levodopa-Induced Dyskinesia. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
Asthmatic Eosinophils Promote Contractility and Migration of Airway Smooth Muscle Cells and Pulmonary Fibroblasts In Vitro
Cells 2021, 10(6), 1389; https://doi.org/10.3390/cells10061389 - 04 Jun 2021
Viewed by 617
Abstract
Enhanced contractility and migration of airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) are part of airway remodeling in asthma. Eosinophils are the central inflammatory cells that participate in airway inflammation. However, the role of asthmatic eosinophils in ASMC and PF contractility, [...] Read more.
Enhanced contractility and migration of airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) are part of airway remodeling in asthma. Eosinophils are the central inflammatory cells that participate in airway inflammation. However, the role of asthmatic eosinophils in ASMC and PF contractility, migration, and differentiation to contractile phenotype has not yet been precisely described. A total of 38 individuals were included in this study: 13 steroid-free non-severe allergic asthma (AA) patients, 11 severe non-allergic eosinophilic asthma (SNEA) patients, and 14 healthy subjects (HS). For AA patients and HS groups, a bronchial allergen challenge with D. pteronyssinus was performed. Individual combined cell cultures were prepared from isolated peripheral blood eosinophils and immortalized ASMC or commercial PF cell lines separately. The migration of ASMC and PF was evaluated using wound healing assay and contractility using collagen gel assay. Gene expression of contractile apparatus proteins, COL1A1, COL5A1, and FN, in ASMC and PF was evaluated using qRT-PCR. We found that contractility and migration of ASMC and PF significantly increased after incubation with asthmatic eosinophils compared to HS eosinophils, p < 0.05, and SNEA eosinophils demonstrated the highest effect on contractility of ASMC and migration of both cell lines, p < 0.05. AA and SNEA eosinophils significantly increased gene expression of contractile apparatus proteins, COL1A1 and FN, in both cell lines, p < 0.05. Furthermore, the allergen-activated AA eosinophils significantly increased the contractility of ASMC, and migration and gene expression in ASMC and PF, p < 0.05. Thus, asthmatic eosinophils change ASMC and PF behavior by increasing their contractility and migration, contributing to airway remodeling. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
Nucleoporin TPR Affects C2C12 Myogenic Differentiation via Regulation of Myh4 Expression
Cells 2021, 10(6), 1271; https://doi.org/10.3390/cells10061271 - 21 May 2021
Cited by 1 | Viewed by 894
Abstract
The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for [...] Read more.
The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
The F-Actin-Binding MPRIP Forms Phase-Separated Condensates and Associates with PI(4,5)P2 and Active RNA Polymerase II in the Cell Nucleus
Cells 2021, 10(4), 848; https://doi.org/10.3390/cells10040848 - 08 Apr 2021
Cited by 1 | Viewed by 801
Abstract
Here, we provide evidence for the presence of Myosin phosphatase rho-interacting protein (MPRIP), an F-actin-binding protein, in the cell nucleus. The MPRIP protein binds to Phosphatidylinositol 4,5-bisphosphate (PIP2) and localizes to the nuclear speckles and nuclear lipid islets which are known to be [...] Read more.
Here, we provide evidence for the presence of Myosin phosphatase rho-interacting protein (MPRIP), an F-actin-binding protein, in the cell nucleus. The MPRIP protein binds to Phosphatidylinositol 4,5-bisphosphate (PIP2) and localizes to the nuclear speckles and nuclear lipid islets which are known to be involved in transcription. We identified MPRIP as a component of RNA Polymerase II/Nuclear Myosin 1 complex and showed that MPRIP forms phase-separated condensates which are able to bind nuclear F-actin fibers. Notably, the fibrous MPRIP preserves its liquid-like properties and reforms the spherical shaped condensates when F-actin is disassembled. Moreover, we show that the phase separation of MPRIP is driven by its long intrinsically disordered region at the C-terminus. We propose that the PIP2/MPRIP association might contribute to the regulation of RNAPII transcription via phase separation and nuclear actin polymerization. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Article
Limited Proteolysis-Coupled Mass Spectrometry Identifies Phosphatidylinositol 4,5-Bisphosphate Effectors in Human Nuclear Proteome
Cells 2021, 10(1), 68; https://doi.org/10.3390/cells10010068 - 04 Jan 2021
Cited by 5 | Viewed by 1414
Abstract
Specific nuclear sub-compartments that are regions of fundamental processes such as gene expression or DNA repair, contain phosphoinositides (PIPs). PIPs thus potentially represent signals for the localization of specific proteins into different nuclear functional domains. We performed limited proteolysis followed by label-free quantitative [...] Read more.
Specific nuclear sub-compartments that are regions of fundamental processes such as gene expression or DNA repair, contain phosphoinositides (PIPs). PIPs thus potentially represent signals for the localization of specific proteins into different nuclear functional domains. We performed limited proteolysis followed by label-free quantitative mass spectrometry and identified nuclear protein effectors of the most abundant PIP—phosphatidylinositol 4,5-bisphosphate (PIP2). We identified 515 proteins with PIP2-binding capacity of which 191 ‘exposed’ proteins represent a direct PIP2 interactors and 324 ‘hidden’ proteins, where PIP2 binding was increased upon trypsin treatment. Gene ontology analysis revealed that ‘exposed’ proteins are involved in the gene expression as regulators of Pol II, mRNA splicing, and cell cycle. They localize mainly to non-membrane bound organelles—nuclear speckles and nucleolus and are connected to the actin nucleoskeleton. ‘Hidden’ proteins are linked to the gene expression, RNA splicing and transport, cell cycle regulation, and response to heat or viral infection. These proteins localize to the nuclear envelope, nuclear pore complex, or chromatin. Bioinformatic analysis of peptides bound in both groups revealed that PIP2-binding motifs are in general hydrophilic. Our data provide an insight into the molecular mechanism of nuclear PIP2 protein interaction and advance the methodology applicable for further studies of PIPs or other protein ligands. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review

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Review
Molecular Interactions Driving Intermediate Filament Assembly
Cells 2021, 10(9), 2457; https://doi.org/10.3390/cells10092457 - 17 Sep 2021
Viewed by 358
Abstract
Given the role of intermediate filaments (IFs) in normal cell physiology and scores of IF-linked diseases, the importance of understanding their molecular structure is beyond doubt. Research into the IF structure was initiated more than 30 years ago, and some important advances have [...] Read more.
Given the role of intermediate filaments (IFs) in normal cell physiology and scores of IF-linked diseases, the importance of understanding their molecular structure is beyond doubt. Research into the IF structure was initiated more than 30 years ago, and some important advances have been made. Using crystallography and other methods, the central coiled-coil domain of the elementary dimer and also the structural basis of the soluble tetramer formation have been studied to atomic precision. However, the molecular interactions driving later stages of the filament assembly are still not fully understood. For cytoplasmic IFs, much of the currently available insight is due to chemical cross-linking experiments that date back to the 1990s. This technique has since been radically improved, and several groups have utilized it recently to obtain data on lamin filament assembly. Here, we will summarize these findings and reflect on the remaining open questions and challenges of IF structure. We argue that, in addition to X-ray crystallography, chemical cross-linking and cryoelectron microscopy are the techniques that should enable major new advances in the field in the near future. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks
Cells 2021, 10(8), 1960; https://doi.org/10.3390/cells10081960 - 02 Aug 2021
Viewed by 634
Abstract
The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm [...] Read more.
The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
Intermediate Filaments from Tissue Integrity to Single Molecule Mechanics
Cells 2021, 10(8), 1905; https://doi.org/10.3390/cells10081905 - 27 Jul 2021
Viewed by 483
Abstract
Cytoplasmic intermediate filaments (IFs), which together with actin and microtubules form the cytoskeleton, are composed of a large and diverse family of proteins. Efforts to elucidate the molecular mechanisms responsible for IF-associated diseases increasingly point towards a major contribution of IFs to the [...] Read more.
Cytoplasmic intermediate filaments (IFs), which together with actin and microtubules form the cytoskeleton, are composed of a large and diverse family of proteins. Efforts to elucidate the molecular mechanisms responsible for IF-associated diseases increasingly point towards a major contribution of IFs to the cell’s ability to adapt, resist and respond to mechanical challenges. From these observations, which echo the impressive resilience of IFs in vitro, we here discuss the role of IFs as master integrators of cell and tissue mechanics. In this review, we summarize our current understanding of the contribution of IFs to cell and tissue mechanics and explain these results in light of recent in vitro studies that have investigated physical properties of single IFs and IF networks. Finally, we highlight how changes in IF gene expression, network assembly dynamics, and post-translational modifications can tune IF properties to adapt cell and tissue mechanics to changing environments. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
The Complement System: A Powerful Modulator and Effector of Astrocyte Function in the Healthy and Diseased Central Nervous System
Cells 2021, 10(7), 1812; https://doi.org/10.3390/cells10071812 - 17 Jul 2021
Cited by 2 | Viewed by 578
Abstract
The complement system, an effector arm of the innate immune system that plays a critical role in tissue inflammation, the elimination of pathogens and the clearance of dead cells and cell debris, has emerged as a regulator of many processes in the central [...] Read more.
The complement system, an effector arm of the innate immune system that plays a critical role in tissue inflammation, the elimination of pathogens and the clearance of dead cells and cell debris, has emerged as a regulator of many processes in the central nervous system, including neural cell genesis and migration, control of synapse number and function, and modulation of glial cell responses. Complement dysfunction has also been put forward as a major contributor to neurological disease. Astrocytes are neuroectoderm-derived glial cells that maintain water and ionic homeostasis, and control cerebral blood flow and multiple aspects of neuronal functioning. By virtue of their expression of soluble as well as membrane-bound complement proteins and receptors, astrocytes are able to both send and receive complement-related signals. Here we review the current understanding of the multiple functions of the complement system in the central nervous system as they pertain to the modulation of astrocyte activity, and how astrocytes use the complement system to affect their environment in the healthy brain and in the context of neurological disease. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis)
Cells 2021, 10(7), 1582; https://doi.org/10.3390/cells10071582 - 23 Jun 2021
Viewed by 687
Abstract
Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear [...] Read more.
Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural organization principle of CHR regulating transcriptional pulsing. The dynamic CHR network is likely created together with nucleolus-associated chromatin domains, while the alveoli of this network, including springy splicing speckles, are the pulsing transcription hubs. CHR contributes to this regulation due to the silencing position variegation effect, stickiness, and flexible rigidity determined by the positioning of nucleosomes. The whole system acts in concert with the elastic nuclear actomyosin network which also emerges by self-organization during the transcriptional pulsing process. We hypothesize that the the transcriptional pulsing, in turn, adjusts its frequency/amplitudes specified by topologically associating domains to the replication timing code that determines epigenetic differentiation memory. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
Neurofilament Light Chain (NfL) in Blood—A Biomarker Predicting Unfavourable Outcome in the Acute Phase and Improvement in the Late Phase after Stroke
Cells 2021, 10(6), 1537; https://doi.org/10.3390/cells10061537 - 18 Jun 2021
Viewed by 559
Abstract
Increased sensitivity of methods assessing the levels of neurofilament light chain (NfL), a neuron-specific intermediate filament protein, in human plasma or serum, has in recent years led to a number of studies addressing the utility of monitoring NfL in the blood of stroke [...] Read more.
Increased sensitivity of methods assessing the levels of neurofilament light chain (NfL), a neuron-specific intermediate filament protein, in human plasma or serum, has in recent years led to a number of studies addressing the utility of monitoring NfL in the blood of stroke patients. In this review, we discuss that elevated blood NfL levels after stroke may reflect several different neurobiological processes. In the acute and post-acute phase after stroke, high blood levels of NfL are associated with poor clinical outcome, and later on, the blood levels of NfL positively correlate with secondary neurodegeneration as assessed by MRI. Interestingly, increased blood levels of NfL in individuals who survived stroke for more than 10 months were shown to predict functional improvement in the late phase after stroke. Whereas in the acute phase after stroke the injured axons are assumed to be the main source of blood NfL, synaptic turnover and secondary neurodegeneration could be major contributors to blood NfL levels in the late phase after stroke. Elevated blood NfL levels after stroke should therefore be interpreted with caution. More studies addressing the clinical utility of blood NfL assessment in stroke patients are needed before the inclusion of NfL in the clinical workout as a useful biomarker in both the acute and the chronic phase after stroke. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
Role of Intermediate Filaments in Blood–Brain Barrier in Health and Disease
Cells 2021, 10(6), 1400; https://doi.org/10.3390/cells10061400 - 05 Jun 2021
Viewed by 733
Abstract
The blood–brain barrier (BBB) is a highly selective cellular monolayer unique to the microvasculature of the central nervous system (CNS), and it mediates the communication of the CNS with the rest of the body by regulating the passage of molecules into the CNS [...] Read more.
The blood–brain barrier (BBB) is a highly selective cellular monolayer unique to the microvasculature of the central nervous system (CNS), and it mediates the communication of the CNS with the rest of the body by regulating the passage of molecules into the CNS microenvironment. Limitation of passage of substances through the BBB is mainly due to tight junctions (TJ) and adherens junctions (AJ) between brain microvascular endothelial cells. The importance of actin filaments and microtubules in establishing and maintaining TJs and AJs has been indicated; however, recent studies have shown that intermediate filaments are also important in the formation and function of cell–cell junctions. The most common intermediate filament protein in endothelial cells is vimentin. Vimentin plays a role in blood–brain barrier permeability in both cell–cell and cell–matrix interactions by affecting the actin and microtubule reorganization and by binding directly to VE-cadherin or integrin proteins. The BBB permeability increases due to the formation of stress fibers and the disruption of VE–cadherin interactions between two neighboring cells in various diseases, disrupting the fiber network of intermediate filament vimentin in different ways. Intermediate filaments may be long ignored key targets in regulation of BBB permeability in health and disease. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
Structural and Functional Modulation of Perineuronal Nets: In Search of Important Players with Highlight on Tenascins
Cells 2021, 10(6), 1345; https://doi.org/10.3390/cells10061345 - 29 May 2021
Viewed by 1006
Abstract
The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an [...] Read more.
The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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Review
The Complexity of FGF23 Effects on Cardiomyocytes in Normal and Uremic Milieu
Cells 2021, 10(5), 1266; https://doi.org/10.3390/cells10051266 - 20 May 2021
Viewed by 722
Abstract
Fibroblast growth factor-23 (FGF23) appears to be one of the most promising biomarkers and predictors of cardiovascular risk in patients with heart disease and normal kidney function, but moreover in those with chronic kidney disease (CKD). This review summarizes the current knowledge of [...] Read more.
Fibroblast growth factor-23 (FGF23) appears to be one of the most promising biomarkers and predictors of cardiovascular risk in patients with heart disease and normal kidney function, but moreover in those with chronic kidney disease (CKD). This review summarizes the current knowledge of FGF23 mechanisms of action in the myocardium in the physiological and pathophysiological state of CKD, as well as its cross-talk to other important signaling pathways in cardiomyocytes. In this regard, current therapeutic possibilities and future perspectives are also discussed. Full article
(This article belongs to the Special Issue Organization and Function of Cellular Structural Networks)
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