The iNKT Cell–Macrophage Axis in Homeostasis and Disease

Invariant natural killer T (iNKT) cells are CD1d-restricted, lipid-reactive T cells that exhibit preponderant immunomodulatory properties. The ultimate protective or deleterious functions displayed by iNKT cells in tissues are known to be partially shaped by the interactions they establish with other immune cells. In particular, the iNKT cell–macrophage crosstalk has gained growing interest over the past two decades. Accumulating evidence has highlighted that this immune axis plays central roles not only in maintaining homeostasis but also during the development of several pathologies. Hence, this review summarizes the reported features of the iNKT cell–macrophage axis in health and disease. We discuss the pathophysiological significance of this interplay and provide an overview of how both cells communicate with each other to regulate disease onset and progression in the context of infection, obesity, sterile inflammation, cancer and autoimmunity.     

Enhancing thermostability by modifying flexible surface loops in an evolved high-redox potential laccase

High-redox potential laccases (HRPLs) from white-rot fungi are versatile biocatalysts whose practical use is highly dependent on their thermostability. In this work, an evolved HRPL variant was subjected to structure-guided evolution to improve its thermostability. We first selected several surface flexible loops in the laccase structure by inspecting them through molecular dynamics and an analysis of B-factors. The resulting segments were grouped into three MORPHING (Mutagenic Organized Recombination Process by Homologous In vivo Grouping) blocks, which were constructed in Saccharomyces cerevisiae and explored at high temperatures. This evolution process gave rise to a double mutant that showed a half-life at 70°C enhanced by 31 min with an optimum temperature for activity of 75°C and similar kinetic parameters. The Ser264Lys and Ser356Asn mutations modified the contacts established between these residues and those that surround them, altering the surface loops and thereby the enzyme properties.     

Enhancement of bioactivity and bioavailability of curcumin with chitosan based materials

Curcumin (CUR) has been investigated for its poor accessibility to a site of action or absorption and rapid metabolism to cope with the limited medication and cure applications. This article reviews numerous approaches, such as encapsulated surfactant/polymeric micelles, liposomes, micro/nano-spheres, nano-suspensions/composites, nanocomplex, films, and hydrogels for effective transfer of CUR to target sites. Chitosan (CS), and chitosan derivatives have been found to enhance therapeutic efficacy of CUR. CS/modified-CS based alginate, cyclodextrin, starch, dextran sulfate, ZnO, phytosomes, and poly(butyl) cyanoacrylate drug delivery matrices improved bioavailability, prolonged drug loading and permeability, sustained release rate, improved solubility and stability (prevent metabolic degradation) of CUR, consequently promoting various clinical applications. CS based polysaccharide, protein, and metal oxide drug delivery nano formulations advantageously participated to improve biological activities of CUR. We have attempted to summarize these delivery approaches, and reviewed future trends/strategies to permit the introduction of CUR as practical therapeutic drug.     

Synthesis of 1‐Naphthol by a Natural Peroxygenase Engineered by Directed Evolution

There is an increasing interest in enzymes that catalyze the hydroxylation of naphthalene under mild conditions and with minimal requirements. To address this challenge, an extracellular fungal aromatic peroxygenase with mono(per)oxygenase activity was engineered to convert naphthalene selectively into 1‐naphthol. Mutant libraries constructed by random mutagenesis and DNA recombination were screened for peroxygenase activity on naphthalene together with quenching of the undesired peroxidative activity on 1‐naphthol (one‐electron oxidation). The resulting double mutant (G241D‐R257K) obtained from this process was characterized biochemically and computationally. The conformational changes produced by directed evolution improved the substrate's catalytic position. Powered exclusively by catalytic concentrations of H₂O₂, this soluble and stable biocatalyst has a total turnover number of 50 000, with high regioselectivity (97 %) and reduced peroxidative activity.     

Formins: Linking Cytoskeleton and Endomembranes in Plant Cells

The cytoskeleton plays a central part in spatial organization of the plant cytoplasm, including the endomebrane system. However, the mechanisms involved are so far only partially understood. Formins (FH2 proteins), a family of evolutionarily conserved proteins sharing the FH2 domain whose dimer can nucleate actin, mediate the co-ordination between actin and microtubule cytoskeletons in multiple eukaryotic lineages including plants. Moreover, some plant formins contain transmembrane domains and participate in anchoring cytoskeletal structures to the plasmalemma, and possibly to other membranes. Direct or indirect membrane association is well documented even for some fungal and metazoan formins lacking membrane insertion motifs, and FH2 proteins have been shown to associate with endomembranes and modulate their dynamics in both fungi and metazoans. Here we summarize the available evidence suggesting that formins participate in membrane trafficking and endomembrane, especially ER, organization also in plants. We propose that, despite some methodological pitfalls inherent to in vivo studies based on (over)expression of truncated and/or tagged proteins, formins are beginning to emerge as candidates for the so far somewhat elusive link between the plant cytoskeleton and the endomembrane system.