Graphical Abstract Biocatalyzed synthesis of difuranosides and their ability to trigger production of TNF-D D Biocatalyzed synthesis of difuranosides and their ability to trigger production of TNF-D D

International audienceTransglycosylation reactions biocatalyzed by the native arabinofuranosidase Araf51 and using D-galactosyl, D-fucosyl and 6-deoxy-6-fluoro-D-galactosyl derivatives as donors and acceptors provided di-to pentahexofuranosides. The immunostimulatory potency of these compounds, and more especially their ability to induce production of TNF-α, was evaluated on the murine macrophage cell line, Raw 264.7. The results obtained showed concentration-dependent and most importantly, structure-dependent responses. Interestingly, oligoarabinofuranosides belonging to the oligopentafuranoside family displayed concentration-, chain length and aglycon-dependent bioactivities irrespective of their fine chemical variations. Thus, neo-oligofuranosides in D-Galf series, as well as their D-Fucf and 6-fluorinated counterparts are indeed potential sources of immunostimulating agents

Prosecco DOC marketing strategies for Chinese market

Table S12. List of all genes within cluster 10. Average log2 transcriptions of individual probe sets under individual treatments are displayed as well as log2 FC of individual treatments against non-treated samples. Manufacturer annotation of individual IDs along with HarvEST annotation of individual AGIs is included. (XLSX 9 kb

Analyzing and Biasing Simulations with PLUMED

This chapter discusses how the PLUMED plugin for molecular dynamics can be used to analyze and bias molecular dynamics trajectories. The chapter begins by introducing the notion of a collective variable and by then explaining how the free energy can be computed as a function of one or more collective variables. A number of practical issues mostly around periodic boundary conditions that arise when these types of calculations are performed using PLUMED are then discussed. Later parts of the chapter discuss how PLUMED can be used to perform enhanced sampling simulations that introduce simulation biases or multiple replicas of the system and Monte Carlo exchanges between these replicas. This section is then followed by a discussion on how free-energy surfaces and associated error bars can be extracted from such simulations by using weighted histogram and block averaging techniques

CH/π Interactions in Carbohydrate Recognition

Many carbohydrate-binding proteins contain aromatic amino acid residues in their binding sites. These residues interact with carbohydrates in a stacking geometry via CH/π interactions. These interactions can be found in carbohydrate-binding proteins, including lectins, enzymes and carbohydrate transporters. Besides this, many non-protein aromatic molecules (natural as well as artificial) can bind saccharides using these interactions. Recent computational and experimental studies have shown that carbohydrate–aromatic CH/π interactions are dispersion interactions, tuned by electrostatics and partially stabilized by a hydrophobic effect in solvated systems

Na+/K+-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation

Maintenance of Na+ and K+ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation

Accelerated RMSD Calculation for Molecular Metadynamics

In this paper, we introduce GPU acceleration of RMSD approximation, which is computationally demanding task in molecular metadynamics. Comparing to tuned CPU implementation, we have reached 4.4x speedup using mid-end GPU. The scaling of our GPU implementation is sufficient to be usable in real-world application

Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin-3: Binding Kinetics and Modeling

Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement in tumor development and proliferation makes this lectin a promising target for early cancer diagnosis and anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins and glycolipids with a high specificity for internal LacNAc epitopes. This study analyzes the mode and kinetics of binding of Gal-3 to a series of multivalent neo-glycoproteins presenting complex poly-LacNAc-based oligosaccharide ligands on a scaffold of bovine serum albumin. These neo-glycoproteins rank among the strongest Gal-3 ligands reported, with Kd reaching sub-nanomolar values as determined by surface plasmon resonance. Significant differences in the binding kinetics were observed within the ligand series, showing the tetrasaccharide capped with N,N′-diacetyllactosamine (LacdiNAc) as the strongest ligand of Gal-3 in this study. A molecular model of the Gal-3 carbohydrate recognition domain with docked oligosaccharide ligands is presented that shows the relations in the binding site at the molecular level. The neo-glycoproteins presented herein may be applied for selective recognition of Gal-3 both on the cell surface and in blood serum