Self-tolerance in multiple sclerosis

During the last decade, several defects in self-tolerance have been identified in multiple sclerosis. Dysfunction in central tolerance leads to the thymic output of antigen-specific T cells with T cell receptor alterations favouring autoimmune reactions. In addition, premature thymic involution results in a reduced export of naïve regulatory T cells, the fully suppressive clone. Alterations in peripheral tolerance concern costimulatory molecules as well as transcriptional and epigenetic mechanisms. Recent data underline the key role of regulatory T cells that suppress Th1 and Th17 effector cell responses and whose immunosuppressive activity is impaired in patients with multiple sclerosis. Those recent observations suggest that a defect in self-tolerance homeostasis might be the primary mover of multiple sclerosis leading to subsequent immune attacks, inflammation and neurodegeneration. The concept of multiple sclerosis as a consequence of the failure of central and peripheral tolerance mechanisms to maintain a self-tolerance state, particularly of regulatory T cells, may have therapeutic implications. Restoring normal thymic output and suppressive functions of regulatory T cells appears an appealing approach. Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56bright natural killer cells

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Femtosecond laser ablation synthesis of chitosan-stabilized copper nanoantimicrobials. In: Physical Chemistry of Functional Biomedical Nanoparticles

Abstracts of paper

Femtosecond laser ablation synthesis of chitosan-stabilized copper nanoantimicrobials, Physical Chemistry of Functional Biomedical Nanoparticles

Nanotechnology, especially nanoparticle research, has played very important roles in many scientific discoverie

Ion Beam Sputtering deposition and characterization of ZnO-fluoropolymer nano-antimicrobials

A new class of nano-antimicrobials was developed by Ion Beam co-Sputtering of ZnO and polytetrafluoro_ ethylene targets. The resulting nanostructured coatings combine the antimicrobial properties of ZnO nanoparticles with the water repellence and anti-stain characters of the dispersing fluoropolymer (CFx). ZnO-CFx nanocomposites were prepared varying ZnO volume fraction (φ) in the CFx matrix by tuning the sputter- ing deposition parameters. Morphological analysis confirmed the presence of homogenously distributed ZnO nanoclusters in the polymer. ZnO loadings ranging in the 0.05-0.15 interval were explored and the nano-composites were characterized by X-ray Photoelectron Spectroscopy (XPS) to investigate their surface chemical composition. XPS spectra evidenced a high degree of polymer defluorina-tion along with the formation of ZnF2 at increasing φ valu-es. Zn speciation was performed on Zn L3M45M45 Auger signal. Coatings bioactivity was assessed against Escheri-chia coli, Staphylococcus aureus, and Kluyveromyces marxianus. At φ ≥ 0.10, ZnO-CFx composites exhibited appreciable antibacterial activity, irrespective of the target organism