-
Computational and Structural... 2023Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological... (Review)
Review
Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological systems fulfill different functions and often form dynamic networks that respond to perturbations. Therefore, characterizing the properties of filamentous structures and the networks they form is important to gain better understanding of systems level functions and dynamics. Filamentous structures are captured by various imaging technologies, and analysis of the resulting imaging data addresses two problems: (i) identification (tracing) of filamentous structures in a single snapshot and (ii) characterizing the dynamics (., tracking) of filamentous structures over time. Therefore, considerable research efforts have been made in developing automated methods for tracing and tracking of filamentous structures. Here, we provide a systematic review in which we present, categorize, and discuss the state-of-the-art methods for tracing and tracking of filamentous structures in sparse and dense networks. We highlight the mathematical approaches, assumptions, and constraints particular for each method, allowing us to pinpoint outstanding challenges and offer perspectives for future research aimed at gaining better understanding of filamentous structures in biological systems.
PubMed: 36618983
DOI: 10.1016/j.csbj.2022.12.023 -
The Ocular Surface Jan 2023Rho kinase inhibitors (ROCKi) have attracted growing multidisciplinary interest, particularly in Ophthalmology where the question as to how they promote corneal... (Review)
Review
A systematic review on the effects of ROCK inhibitors on proliferation and/or differentiation in human somatic stem cells: A hypothesis that ROCK inhibitors support corneal endothelial healing via acting on the limbal stem cell niche.
Rho kinase inhibitors (ROCKi) have attracted growing multidisciplinary interest, particularly in Ophthalmology where the question as to how they promote corneal endothelial healing remains unresolved. Concurrently, stem cell biology has rapidly progressed in unravelling drivers of stem cell (SC) proliferation and differentiation, where mechanical niche factors and the actin cytoskeleton are increasingly recognized as key players. There is mounting evidence from the study of the peripheral corneal endothelium that supports the likelihood of an internal limbal stem cell niche. The possibility that ROCKi stimulate the endothelial SC niche has not been addressed. Furthermore, there is currently a paucity of data that directly evaluates whether ROCKi promotes corneal endothelial healing by acting on this limbal SC niche located near the transition zone. Therefore, we performed a systematic review examining the effects ROCKi on the proliferation and differentiation of human somatic SC, to provide insight into its effects on various human SC populations. An appraisal of electronic searches of four databases identified 1 in vivo and 58 in vitro studies (36 evaluated proliferation while 53 examined differentiation). Types of SC studied included mesenchymal (n = 32), epithelial (n = 11), epidermal (n = 8), hematopoietic and other (n = 8). The ROCK 1/2 selective inhibitor Y-27632 was used in almost all studies (n = 58), while several studies evaluated ≥2 ROCKi (n = 4) including fasudil, H-1152, and KD025. ROCKi significantly influenced human somatic SC proliferation in 81% of studies (29/36) and SC differentiation in 94% of studies (50/53). The present systemic review highlights that ROCKi are influential in regulating human SC proliferation and differentiation, and provides evidence to support the hypothesis that ROCKi promotes corneal endothelial division and maintenance via acting on the inner limbal SC niche.
Topics: Humans; Endothelium, Corneal; Limbal Stem Cells; Adult Stem Cells; Cell Differentiation; Cell Proliferation; Limbus Corneae; Epithelium, Corneal; Stem Cell Niche
PubMed: 36586668
DOI: 10.1016/j.jtos.2022.12.008 -
Journal of Cancer 2022Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the... (Review)
Review
Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the structural plasticity of dendrites and spines. Members of the Rho-GTPase family include Ras-related C3 botulinum toxin substrate 1 (Rac1), RhoA (Ras homologous), and cell division control protein 42 (Cdc42). Cdc42 is involved in the regulation of a variety of tumor and non-tumor diseases through a cascade of multiple signaling pathways. Active Cdc42 can regulate intercellular adhesion, cytoskeleton formation, and cell cycle, thus affecting cell proliferation, transformation, and dynamic balance as well as migration and invasion of tumor cells by regulating the expression of effector proteins. Here we discuss the role of Cdc42 in promoting metastasis, invasion, epithelial-mesenchymal transformation and angiogenesis in malignant tumors. The significant role of Cdc42 in non-tumor diseases is also discussed. Since Cdc42 plays a central role in the development of various diseases, small molecule inhibitors targeting Cdc42 have important clinical significance in the prevention and treatment of these diseases.
PubMed: 35154449
DOI: 10.7150/jca.65415 -
International Journal of Molecular... Nov 2021Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of... (Review)
Review
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.
Topics: Actin Cytoskeleton; Bacterial Toxins; Cell Line; Enterotoxins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; rho GTP-Binding Proteins
PubMed: 34830494
DOI: 10.3390/ijms222212610 -
Frontiers in Endocrinology 2020Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the...
BACKGROUND
Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the collective morphological and molecular alterations occurring to the endometrial luminal epithelium across the mid-secretory phase of the menstrual cycle to facilitate implantation. Dysregulation of this process directly affects endometrial receptivity and implantation. Multiple parallels between these alterations to confer endometrial receptivity in women have been drawn to those seen during the epithelial-mesenchymal transition (EMT) in tumorigenesis. Understanding these similarities and differences will improve our knowledge of implantation biology, and may provide novel therapeutic targets to manage implantation failure.
METHODS
A systematic review was performed using the Medline (Ovid), Embase, and Web of Science databases without additional limits. The search terms used were "(plasma membrane* or cell membrane*) and transformation*" and "endometrium or endometrial." Research studies on the PMT or its regulation in women, discussing either the endometrial epithelium, decidualized stroma, or both, were eligible for inclusion.
RESULTS
A total of 198 articles were identified. Data were extracted from 15 studies that matched the inclusion criteria. Collectively, these included studies confirmed the alterations occurring to the endometrial luminal epithelium during the PMT are similar to those seen during the EMT. Such similarities included alterations to the actin cytoskeleton remodeling of adherens junctions, integrin expression and epithelial-stromal communication. These were also some differences between these processes, such as the regulation of tight junctions and mucins, which need to be further researched.
CONCLUSIONS
This review raised the prospect of shared and distinct mechanisms existing in PMT and EMT. Further investigation into similarities between the PMT in the endometrium and the EMT in tumorigenesis may provide new mechanistic insights into PMT and new targets for the management of implantation failure and infertility.
Topics: Animals; Cell Polarity; Embryo Implantation; Endometrium; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Humans
PubMed: 33193109
DOI: 10.3389/fendo.2020.596324 -
Clinical Journal of the American... Oct 2018Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact...
BACKGROUND AND OBJECTIVES
Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys.
RESULTS
We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies (=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (=17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.
CONCLUSIONS
A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.
Topics: Environmental Exposure; Environmental Pollutants; Fluorocarbon Polymers; Humans; Kidney Diseases
PubMed: 30213782
DOI: 10.2215/CJN.04670418 -
Methods in Molecular Biology (Clifton,... 2018The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing...
The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing and regulation of actin cytoskeleton. Over the past decades, accumulating experimental work has increasingly mapped out the mechanistic details and interactions between members of the family and their regulators, establishing detailed interaction circuits within the Rho GTPase signaling network. These circuits have served as a vital foundation based on which a multitude of mathematical models have been developed to explain experimental data, gain deeper insights into the biological phenomenon they describe, as well as make new testable predictions and hypotheses. Due to the diverse nature and purpose of these models, they often vary greatly in size, scope, complexity, and formulation. Here, we provide a systematic, categorical, and comprehensive account of the recent modeling studies of Rho family GTPases, with an aim to offer a broad perspective of the field. The modeling limitations and possible future research directions are also discussed.
Topics: Animals; Computer Simulation; Humans; Models, Biological; Signal Transduction; rho GTP-Binding Proteins
PubMed: 30062401
DOI: 10.1007/978-1-4939-8612-5_1 -
Developmental Neurobiology Oct 2014The functions of microtubule-associated protein 1B (MAP1B) have historically been linked to the development of the nervous system, based on its very early expression in... (Review)
Review
The functions of microtubule-associated protein 1B (MAP1B) have historically been linked to the development of the nervous system, based on its very early expression in neurons and glial cells. Moreover, mice in which MAP1B is genetically inactivated have been used extensively to show its role in axonal elongation, neuronal migration, and axonal guidance. In the last few years, it has become apparent that MAP1B has other cellular and molecular functions that are not related to its microtubule-stabilizing properties in the embryonic and adult brain. In this review, we present a systematic review of the canonical and novel functions of MAP1B and propose that, in addition to regulating the polymerization of microtubule and actin microfilaments, MAP1B also acts as a signaling protein involved in normal physiology and pathological conditions in the nervous system.
Topics: Animals; Brain; Humans; Microtubule-Associated Proteins; Myasthenia Gravis; Neurons
PubMed: 24700609
DOI: 10.1002/dneu.22178