Air pollution has increased over the years, causing a negative impact on society due to the many health-related problems it can contribute to. Although the type and extent of air pollutants are ...known, the molecular mechanisms underlying the induction of negative effects on the human body remain unclear. Emerging evidence suggests the crucial involvement of different molecular mediators in inflammation and oxidative stress in air pollution-induced disorders. Among these, non-coding RNAs (ncRNAs) carried by extracellular vesicles (EVs) may play an essential role in gene regulation of the cell stress response in pollutant-induced multiorgan disorders. This review highlights EV-transported ncRNAs' roles in physiological and pathological conditions, such as the development of cancer and respiratory, neurodegenerative, and cardiovascular diseases following exposure to various environmental stressors.
Across diverse habitats, bacteria are mainly found as biofilms, surface-attached communities embedded in a self-secreted matrix of extracellular polymeric substances (EPS), which enhance bacterial ...recalcitrance to antimicrobial treatment and mechanical stresses. In the presence of flow and geometric constraints such as corners or constrictions, biofilms can take the form of long, suspended filaments (streamers), which bear important consequences in industrial and clinical settings by causing clogging and fouling. The formation of streamers is thought to be driven by the viscoelastic nature of the biofilm matrix. Yet, little is known about the structural composition of streamers and how it affects their mechanical properties. Here, using a microfluidic platform that allows growing and precisely examining biofilm streamers, we show that extracellular DNA (eDNA) constitutes the backbone and is essential for the mechanical stability of Pseudomonas aeruginosa streamers. This finding is supported by the observations that DNA-degrading enzymes prevent the formation of streamers and clear already formed ones and that the antibiotic ciprofloxacin promotes their formation by increasing the release of eDNA. Furthermore, using mutants for the production of the exopolysaccharide Pel, an important component of P. aeruginosa EPS, we reveal an concurring role of Pel in tuning the mechanical properties of the streamers. Taken together, these results highlight the importance of eDNA and of its interplay with Pel in determining the mechanical properties of P. aeruginosa streamers and suggest that targeting the composition of streamers can be an effective approach to control the formation of these biofilm structures.
The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A ...malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic NCPs are linked to pathogenic variants of chaperone genes encoding, for example, the small Hsp, Hsp10, Hsp40, Hsp60, and CCT-BBS (chaperonin-containing TCP-1- Bardet–Biedl syndrome) chaperones. Instead, the acquired NCPs are associated with malfunctional chaperones, such as Hsp70, Hsp90, and VCP/p97 with aberrant post-translational modifications. Awareness of the chaperonopathies as the underlying primary or secondary causes of disease will improve diagnosis and patient management and open the possibility of investigating and developing chaperonotherapy, namely treatment with the abnormal chaperone as the main target. Positive chaperonotherapy would apply in chaperonopathies by defect, i.e., chaperone insufficiency, and consist of chaperone replacement or boosting, whereas negative chaperonotherapy would be pertinent when a chaperone actively participates in the initiation and progression of the disease and must be blocked and eliminated.
Two chaperonopathies have been linked to mutations in the human
hsp60
(
hHsp60
;
HSPD1
) gene, but other existing variants might cause diseases, even if there is no comprehensive information about ...this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single
hsp60
gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possible impact on protein structure-function, considering: (a) the properties of individual amino acids; (b) the known functions of the amino acids in the human Hsp60 and/or in the highly similar bacterial ortholog GroEL; (c) the location of the mutant amino acids in the monomers and oligomers; and (d) structure-function relationships inferred from crystal structures. And we also applied a bioinformatics tool for predicting the impact of mutations on proteins. A portion of these genetic variants could have a deleterious impact on protein structure-function, but have not yet been associated with any pathology. Are these variants causing disease with mild clinical manifestations and are, therefore, being overlooked? Or are they causing overt disease, which is misdiagnosed? Our data indicate that more chaperonopathies might occur than is currently acknowledged and that awareness of chaperonopathies among medical personnel will increase their detection and improve patient management.
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•Chitosan/poly(eyhylene oxide) nanofibers are obtained by electrospinning.•Successful photo-crosslinking of the nanofiber mats is performed.•Morphological and thermal properties are ...preserved after the irradiation process.•Photo-crosslinking increases the solvent resistance of the nanofiber mats.•Nanofibers retain their nanostructure morphology after water contact.
Photo-crosslinked nanofiber mats containing chitosan were obtained through the versatile and promising technology of electrospinning. Due to the challenging processability of chitosan by electrospinning because of its stiffness and polycationic nature, it was blended with easily-spinnable poly(ethylene oxide). The optimum conditions for electrospinning of chitosan/poly(eyhylene oxide) (CS/PEO) blends were selected for further characterization and investigation: the composition of CS/PEO 70/30 mass fraction was chosen as it allowed to produce uniform and defect free electrospun mats formed by fibers with an average diameter of 270 nm. In order to improve the physico-chemical properties (in particular the stability and water resistance) of the electrospun mats, electrospinning was coupled with the fast and eco-friendly technique of photo-crosslinking. The photo-curing reaction of the CS/PEO fibers, as well as the morphology, thermal properties and water resistance of the electrospun mats before and after application of UV irradiation, were investigated. The photo-crosslinking process was optimized in order to fabricate CS/PEO electrospun mats which are resistant to water and thus can enlarge the application of such membranes, especially in biomedical, filtration and food industries.
Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s ...proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasma-cell membrane, and extracellular vesicles (EVs). Consequently, non-canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi-faceted role of this chaperonin in human cancers, showing the contribution of intra- and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA-mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti-cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro- or anti-tumor.
We demonstrate how to tune the surface chemistry and properties of copolymers obtained by the photopolymerization of polyoxyethylene (meth)acrylic monomers and a low polarity siloxane comonomer ...which spontaneously migrates to the free surface. By controlling the photopolymerization conditions, such as the light gradient through the thickness of the film and selecting the proper monomer functionality, it is possible to optimize and photoenforce the surface segregation of the siloxane comonomer. Photocured films containing the same amount of siloxane component (1 wt %) can exhibit a surface energy ranging from 42 to 22 mN m–1 depending on the process conditions. XPS and AFM analyses confirm that polymers with a compositional gradient are obtained and that the surface segregation can be finely photocontrolled. Photopolymerization is thus proven to be a facile, single step method for generating gradient films and for independently and simultaneously tune their surface and bulk properties.
Summary
Members of the genus Burkholderia show remarkable abilities to adapt to a wide range of environmental conditions and is frequently isolated from soils contaminated with heavy metals. In this ...study, we used a transposon sequencing approach to identify 138 and 164 genes that provide a benefit for growth of the opportunistic pathogen Burkholderia cenocepacia H111 in the presence of silver and gold ions respectively. The data suggest that arginine metabolism and citrate biosynthesis are important for silver tolerance, while components of an ABC transporter (BCAL0307‐BCAL0308) and de novo cysteine biosynthesis are required for tolerance to gold ions. We show that determinants that affect tolerance to both metal ions include the two‐component systems BCAL0497/99 and BCAL2830/31 and genes that are involved in maintaining the integrity of the cell envelope, suggesting that membrane proteins represent important targets of silver and gold ions. Furthermore, we show that that the P‐type ATPase CadA (BCAL0055), which confers tolerance to cadmium contributes to silver but not gold tolerance. Our results may be useful for improving the antibacterial effect of silver and gold ions to combat drug‐resistant pathogens.
Members of the genus Burkholderia show remarkable abilities to adapt to a wide range of environmental conditions and is frequently isolated from soils contaminated with heavy metals. In this study, ...we used a transposon sequencing approach to identify 138 and 164 genes that provide a benefit for growth of the opportunistic pathogen Burkholderia cenocepacia H111 in the presence of silver and gold ions respectively. The data suggest that arginine metabolism and citrate biosynthesis are important for silver tolerance, while components of an ABC transporter (BCAL0307‐BCAL0308) and de novo cysteine biosynthesis are required for tolerance to gold ions. We show that determinants that affect tolerance to both metal ions include the two‐component systems BCAL0497/99 and BCAL2830/31 and genes that are involved in maintaining the integrity of the cell envelope, suggesting that membrane proteins represent important targets of silver and gold ions. Furthermore, we show that that the P‐type ATPase CadA (BCAL0055), which confers tolerance to cadmium contributes to silver but not gold tolerance. Our results may be useful for improving the antibacterial effect of silver and gold ions to combat drug‐resistant pathogens.
Recognition of diseases associated with mutations of the chaperone system genes, e.g., chaperonopathies, is on the rise. Hereditary and clinical aspects are established, but the impact of the ...mutation on the chaperone molecule and the mechanisms underpinning the tissue abnormalities are not. Here, histological features of skeletal muscle from a patient with a severe, early onset, distal motor neuropathy, carrying a mutation on the CCT5 subunit (MUT) were examined in comparison with normal muscle (CTR). The MUT muscle was considerably modified; atrophy of fibers and disruption of the tissue architecture were prominent, with many fibers in apoptosis. CCT5 was diversely present in the sarcolemma, cytoplasm, and nuclei in MUT and in CTR and was also in the extracellular space; it colocalized with CCT1. In MUT, the signal of myosin appeared slightly increased, and actin slightly decreased as compared with CTR. Desmin was considerably delocalized in MUT, appearing with abnormal patterns and in precipitates. Alpha-B-crystallin and Hsp90 occurred at lower signals in MUT than in CTR muscle, appearing also in precipitates with desmin. The abnormal features in MUT may be the consequence of inactivity, malnutrition, denervation, and failure of protein homeostasis. The latter could be at least in part caused by malfunction of the CCT complex with the mutant CCT5 subunit. This is suggested by the results of the
in silico
analyses of the mutant CCT5 molecule, which revealed various abnormalities when compared with the wild-type counterpart, mostly affecting the apical domain and potentially impairing chaperoning functions. Thus, analysis of mutated CCT5
in vitro
and
in vivo
is anticipated to provide additional insights on subunit involvement in neuromuscular disorders.
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