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 Escherichia coli 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.

During signal transduction, multivalent interactions establish dynamic molecular connectivities that propagate molecular cascades throughout the entire signaling pathway. Such multivalent interactions include the initial activation, cascade signal transduction, and the amplification and assembly of structural machinery. For example, plants rapidly remodel the actin cytoskeleton during signal transduction by perceiving a wide range of mechanical and chemical cues from developmental and defense pathways. Actin treadmilling is stepwise-regulated by interactions between actin and actin-binding proteins (ABPs). Emerging evidence shows that intrinsically disordered regions (IDRs) enable flexible and promiscuous interactions that serve as the functional hub for generating cellular interactomes underlying various signaling events. Though IDRs are present in a majority of ABPs, few of the functional roles of IDR in the interaction and functions of ABPs have been defined. The distinct features of IDRs create diverse and dynamic molecular interactions that introduce a new paradigm to our understanding of the structure-function relationships for actin assembly. In this review, we will create a snapshot of recent advances in IDR-mediated plant actin remodeling and discuss future research directions in studying the complexity of actin assembly via multifaceted biomolecular assembly during signal transduction.

Since time immemorial, tuberculosis (TB) has intimidated the human race owing to its severity. Its socio-economic burden has led to it being a major cause of concern. It is one of the world\'s major causes of death from a single agent. Since most of the middle- and low-income countries are burdened with TB, sputum smear examination using conventional light microscopy is often the only resort for diagnosing TB. However, fluorescence microscopy is used as standard in most high-income countries, owing to its increased sensitivity. Light-emitting diodes (LEDs), being inexpensive, are increasingly gaining popularity as an alternative light source for fluorescence microscopy. It has been found to be highly efficient and has a lot of advantages over the conventional Ziehl-Neelsen-based bright field microscopy. In this review, we discuss about the usefulness of LED-based fluorescence microscopy in diagnosing TB and how it is superior to the other sources of light used.

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.
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.
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 (n=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (n=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (n=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.
A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.

This short review article summarizes what is known clinically and biochemically about the seven human NADPH oxidases. Emphasis is put on the connection between mutations in the catalytic and regulatory subunits of Nox2, the phagocyte defense enzyme, with syndromes like chronic granulomatous disease, as well as a number of chronic inflammatory diseases. These arise paradoxically from a lack of reactive oxygen species production needed as second messengers for immune regulation. Both Nox2 and the six other human NADPH oxidases display signaling functions in addition to the functions of these enzymes in specialized biochemical reactions, for instance, synthesis of the hormone thyroxine. NADPH oxidases are also needed by Saccharomyces cerevisiae cells for the regulation of the actin cytoskeleton in times of stress or developmental changes, such as pseudohyphae formation. The article shows that in certain cancer cells Nox4 is also involved in the re-structuring of the actin cytoskeleton, which is required for cell mobility and therefore for metastasis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients\' skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novel in vitro ALS tissue-engineered skin model, derived from patients, for the study of ALS.

Motility is a requirement for a number of biological processes, including embryonic development, neuronal development, immune responses, cancer progression and wound healing. Specific to wound healing is the migration of endothelial cells, fibroblasts and other key cellular players into the wound space. Aberrations in wound healing can result in either chronic wounds or abnormally healed wounds. The protein 4.1R, ezrin, radixin, moesin (FERM) superfamily consists of over 40 proteins all containing a three lobed N-terminal FERM domain which binds a variety of cell-membrane associated proteins and lipids. The C-terminal ends of these proteins typically contain an actin-binding domain (ABD). These proteins therefore mediate the linkage between the cell membrane and the actin cytoskeleton, and are involved in cellular movements and migration. Certain FERM proteins have been shown to promote cancer metastasis via this very mechanism. Herein we review the effects of a number of FERM proteins on wound healing and cancer. We show how these proteins typically aid wound healing through their effects on increasing cellular migration and movements, but also typically promote metastasis in cancer. We conclude that FERM proteins play important roles in cellular migration, with markedly different outcomes in the context of cancer and wound healing.

Human immunodeficiency virus (HIV)-1 has been detected in ocular tissues; however, the mechanism of entry has not been established. It has been hypothesized that the blood-retinal barrier (BRB), a critical guardian against microbial invasion of the eye, may be compromised in the presence of HIV-1 in the eye. In vivo and in vitro model systems have shown that the breach of tight junctions induced by HIV-1-associated factors contributes to the breakdown of the BRB. The present study reviews the mechanism of tight junction disruption, focusing on signaling pathways, the expression of enzymes, including metalloproteinases, and cytokines that affect inflammation. The studied pathways may be potential targets for the prevention of ocular HIV complications.

A characteristic feature of motile cells as they undergo a change in motile behavior is the development of fluctuating exploratory motions of the leading edge, driven by actin polymerization. We review quantitative models of these protrusion and retraction phenomena. Theoretical studies have been motivated by advances in experimental and computational methods that allow controlled perturbations, single molecule imaging, and analysis of spatiotemporal correlations in microscopic images. To explain oscillations and waves of the leading edge, most theoretical models propose nonlinear interactions and feedback mechanisms among different components of the actin cytoskeleton system. These mechanisms include curvature-sensing membrane proteins, myosin contraction, and autocatalytic biochemical reaction kinetics. We discuss how the combination of experimental studies with modeling promises to quantify the relative importance of these biochemical and biophysical processes at the leading edge and to evaluate their generality across cell types and extracellular environments.

This paper reviews current knowledge on the distribution and mobility of water in muscle (myowater) ante- and post mortem and factors affecting these in relation to fresh meat quality parameters; water-holding capacity (WHC), tenderness and juiciness. NMR transverse relaxometry (T(2)) using bench-top Low-Field Nuclear Magnetic Resonance (LF-NMR) has characterised myowater distribution and mobility as well as structural features in meat which directly affect WHC. The current literature demonstrates that WHC is correlated to the water located outside the myofibrillar network (extra-myofibrillar). This review identifies the critical stages which affect the translocation of water into the extra-myofibrillar space and thus the potential for decreased WHC during proteolysis (the conversion of muscle to meat). This review discusses how the intrinsic properties of the water held within the meat could contribute to juiciness and tenderness. Tenderness has been shown to correlate to T(2), however breed and species differences made it difficult to draw firm conclusions. Further understanding of the inherent water properties of fresh meat and the factors affecting water distribution and mobility using NMR technologies will increase the understanding of WHC and tenderisation of fresh meat.