Unravelling the Time Scale of Conformational Plasticity and Allostery in Glycan Recognition by Human Galectin-1

The interaction of human galectin-1 with a variety of oligosaccharides, from di-(N-acetyllactosamine) to tetra-saccharides (blood B type-II antigen) has been scrutinized by using a combined approach of different NMR experiments, molecular dynamics (MD) simulations, and isothermal titration calorimetry. Ligand- and receptor-based NMR experiments assisted by computational methods allowed proposing three-dimensional structures for the different complexes, which explained the lack of enthalpy gain when increasing the chemical complexity of the glycan. Interestingly, and independently of the glycan ligand, the entropy term does not oppose the binding event, a rather unusual feature for protein-sugar interactions. CLEANEX-PM and relaxation dispersion experiments revealed that sugar binding affected residues far from the binding site and described significant changes in the dynamics of the protein. In particular, motions in the microsecond-millisecond timescale in residues at the protein dimer interface were identified in the presence of high affinity ligands. The dynamic process was further explored by extensive MD simulations, which provided additional support for the existence of allostery in glycan recognition by human galectin-1.     

Simple HPLC‐UV for the quantification of a new leishmanicidal candidate (E)‐1‐4(trifluoromethyl) benzylidene)‐5‐(2‐4‐dichlorozoyl) carbonylhydrazine (LASSBio‐1736) in rat plasma for pharmacokinetics assessment

In this study, a sensitive HPLC‐UV assay was developed and validated for the determination of LASSBio‐1736 in rat plasma with sodium diclofenac as internal standard (IS). Liquid–liquid extraction using acetonitrile was employed to extract LASSBio‐1736 and IS from 100 μL of plasma previously basified with NaOH 0.1 M. Chromatographic separation was carried on Waters Spherisorb^®S5 ODS2 C₁₈ column (150 × 4.6 mm, 5 μm) using an isocratic mobile phase composed by water with triethylamine 0.3% (pH 4), methanol and acetonitrile grade (45:15:40, v/v/v) at a flow rate of 1 mL/min. Both LASSBio‐1736 and IS were eluted at 4.2 and 5 min, respectively, with a total run time of 8 min only. The lower limit of quantification was 0.2 μg/mL and linearity between 0.2 and 4 μg/mL was obtained, with an R² > 0.99. The accuracy of the method was >90.5%. The relative standard deviations intra and interday were <6.19 and <7.83%, respectively. The method showed the sensitivity, linearity, precision, accuracy and selectivity required to quantify LASSBio‐1736 in preclinical pharmacokinetic studies according to the criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright © 2016 John Wiley & Sons, Ltd.     

Photodynamic Therapy and Immunity: An Update

Dr. Thomas Dougherty and his Oncology Foundation of Buffalo were the first to support my (S.O.G.) research into the effects of photodynamic therapy (PDT) on the host immune system. The small grant I was awarded in 2002 launched my career as an independent researcher; at the time, there were few studies on the importance of the immune response on the efficacy of PDT and no studies demonstrating the ability of PDT to enhance antitumor immunity. Over the last decades, the interest in PDT as an enhancer of antitumor immunity and our understanding of the mechanisms by which PDT enhances antitumor immunity have dramatically increased. In this review article, we look back on the studies that laid the foundation for our understanding and provide an update on current advances and therapies that take advantage of PDT enhancement of immunity.     

Highly corrosion resistant siloxane-polymethyl methacrylate hybrid coatings

Siloxane-polymethyl methacrylate hybrid films were deposited on carbon steel substrates by dip-coating from a sol prepared by acid-catalyzed hydrolytic co-polycondensation of tetraethoxysilane (TEOS) and 3-methacryloxy propyl-trimethoxysilane (MPTS), followed by radical polymerization of methyl methacrylate (MMA). Structural properties of the hybrids were studied using ²⁹Si and ¹³C nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA), as a function of the MMA/MPTS ratio, which ranged between 2 and 10. The efficiency of corrosion protection of hybrid-coated carbon steel was investigated by XPS, potentiodynamic polarization curves and electrochemical impedance spectroscopy after immersion of the material in acidic and neutral saline aqueous solution. The NMR and TGA results indicate a high degree of polycondensation (84%) and elevated thermal stability of 410?°C for the hybrid film with a MMA/MPTS ratio of 8, exhibiting also and excellent adhesion to the substrate. The XPS analysis confirmed the variation of the MMA phase in the hybrid, and showed that no corrosion-induced changes had occurred after 18?days immersion of the coated steel in 3.5% NaCl solution. Potentiodynamic polarization curves have shown that the hybrid coating prepared using a TEOS/MPTS ratio of 8 yielded the best anti-corrosion performance. It acts as a very efficient corrosion barrier, increasing the total impedance by almost 6 orders of magnitude and reducing the current densities by 4 orders of magnitude, compared to the bare electrode. The obtained results are discussed based on the correlation of structural information with impedance data presented for both electrolytes in the form of electrical equivalent circuits.     

Extremal Curves in Nilpotent Lie Groups

We classify extremal curves in free nilpotent Lie groups. The classification is obtained via an explicit integration of the adjoint equation in Pontryagin maximum principle. It turns out that abnormal extremals are precisely the horizontal curves contained in algebraic varieties of a specific type. We also extend the results to the nonfree case.     

On the Local Convergence Analysis of the Gradient Sampling Method for Finite Max-Functions

The gradient sampling method is a recently developed tool for solving unconstrained nonsmooth optimization problems. Using just first-order information about the objective function, it generalizes the steepest descent method, one of the most classical methods for minimizing a smooth function. This study aims at determining under which circumstances one can expect the same local convergence result of the Cauchy method for the gradient sampling algorithm under the assumption that the problem is stated by a finite max-function around the optimal point. Additionally, at the end, we show how to practically accomplish the required hypotheses during the execution of the algorithm.