An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network

Galectins, a family of evolutionarily conserved animal lectins, have been shown to modulate signaling processes leading to inflammation, apoptosis, immunoregulation, and angiogenesis through their ability to interact with poly-N-acetyllactosamine-enriched glycoconjugates. To date 16 human galectin carbohydrate recognition domains have been established by sequence analysis and found to be expressed in several tissues. Given the divergent functions of these lectins, it is of vital importance to understand common and differential features in order to search for specific inhibitors of individual members of the human galectin family. In this work we performed an integrated computational analysis of all individual members of the human galectin family. In the first place, we have built homology-based models for galectin-4 and -12 N-terminus, placental protein 13 (PP13) and PP13-like protein for which no experimental structural information is available. We have then performed classical molecular dynamics simulations of the whole 15 members family in free and ligand-bound states to analyze protein and protein-ligand interaction dynamics. Our results show that all galectins adopt the same fold, and the carbohydrate recognition domains are very similar with structural differences located in specific loops. These differences are reflected in the dynamics characteristics, where mobility differences translate into entropy values which significantly influence their ligand affinity. Thus, ligand selectivity appears to be modulated by subtle differences in the monosaccharide binding sites. Taken together, our results may contribute to the understanding, at a molecular level, of the structural and dynamical determinants that distinguish individual human galectins.     

Absolute protein quantification by LC-ICP-MS using MeCAT peptide labeling

Nowadays, the most common strategies used in quantitative proteomics are based on isotope-coded labeling followed by specific molecule mass spectrometry. The implementation of inductively coupled plasma mass spectrometry (ICP-MS) for quantitative purposes can solve important drawbacks such as lack of sensitivity, structure-dependent responses, or difficulties in absolute quantification. Recently, lanthanide-containing labels as metal-coded affinity tag (MeCAT) reagents have been introduced, increasing the interest and scope of elemental mass spectrometry techniques for quantitative proteomics. In this work one of the first methodologies for absolute quantification of peptides and proteins using MeCAT labeling is presented. Liquid chromatography (LC) interfaced to ICP-MS has been used to separate and quantify labeled peptides while LC coupled to electrospray ionization mass spectrometry served for identification tasks. Synthetic-labeled peptides were used as standards to calibrate the response of the detector with compounds as close as possible to the target species. External calibration was employed as a quantification technique. The first step to apply this approach was MeCAT-Eu labeling and quantification by isotope dilution ICP-MS of the selected peptides. The standards were mixed in different concentrations and subjected to reverse-phase chromatography before ICP-MS detection to consider the column effect over the peptides. Thus, the prepared multi-peptide mix allowed a calibration curve to be obtained in a single chromatographic run, correcting possible non-quantitative elutions of the peptides from the column. The quantification strategy was successfully applied to other labeled peptides and to standard proteins such as digested lysozyme and bovine serum albumin.     

Morphological,electrochemical and photoelectrochemical characterization of nanotubular TiO2 synthetized electrochemically from different electrolytes

The electrochemical synthesis of auto-organized TiO₂ arrays generated by Ti anodization in different non-aqueous electrolytes was analyzed. Propylene carbonate-based electrolytes seem to be good electrolytic media for the controlled growth of titania nanotube structures. Scanning electron microscopy (SEM) analysis indicated that, depending on the media employed in the synthesis of the TiO₂ nanotubes, different aspect ratios (length/diameter) could be obtained. Impedance analysis using the passive pit model gave the electrical properties of the layers during the different stages of nanotubes formation. Mott–Schottky analysis and the impedance results showed that the TiO₂ nanotubes layers were n-type semiconductors with highly defective walls on top of a resistive barrier layer. Photoelectrochemical measurements showed that tetra(4-carboxyphenyl)porphyrin (TCPP) adsorbed onto the TiO₂ nanotube arrays, which could be employed as an efficient photosensitizer for solar-energy conversion by TCPP-sensitized nanotubular TiO₂ electrodes.     

Computational exploration of natural sunscreens

The photoprotective role of a family of compounds found in very different organisms is assessed by means of CASPT2//CASSCF computations. The potential use of these compounds in commercial applications in order to effectively dissipate light energy is explored.     

Supramolecular construction of vesicles based on core-substituted naphthalene diimide appended with triethyleneglycol motifs

The self-assembly of core-substituted naphthalene diimides bearing triethylene glycol motifs leads to the formation of stable vesicles in DMSO and CHCl(3)/MeOH (6?:?4, v/v) solvents. The vesicles were evaluated by means of UV/vis and fluorescence spectroscopy, transmission electron microscopy, atomic force microscopy and dynamic light scattering.     

Palladium(II) complex with S-allyl-L-cysteine: new solid-state NMR spectroscopic measurements, molecular modeling and antibacterial assays

Nuclear magnetic resonance studies, molecular modeling and antibacterial assays of the palladium(II) complex with S-allyl-L-cysteine (deoxyalliin) are presented. Studies based on solid and solution 13C and 15N nuclear magnetic resonance (NMR) spectroscopy confirmed that the palladium(II) complex preserved the same structural arrangement in both states, with no modifications on coordination sphere when dissolved in water. Density functional theory (DFT) studies stated that the trans isomer is the most stable one. Antibacterial activities of S-allyl-L-cysteine and its palladium(II) complex were evaluated by antibiogram assays using the disc diffusion method. The palladium(II) complex showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive), Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial cells.     

Half-flat nilmanifolds

We introduce a double complex that can be associated to certain Lie algebras, and show that its cohomology determines an obstruction to the existence of a half-flat SU(3)-structure. We obtain a classification of the 6-dimensional nilmanifolds carrying an invariant half-flat structure.     

Solvable Lie algebras are not that hypo

We study a type of left-invariant structure on Lie groups or, equivalently, on Lie algebras. We introduce obstructions to the existence of a hypo structure, namely the five-dimensional geometry of hypersurfaces in manifolds with holonomy SU(3). The choice of a splitting \mathfrakg^* = V₁ ?V₂ {\mathfrak{g}^*} = {V_1} \oplus {V_2} , and the vanishing of certain associated cohomology groups, determine a first obstruction. We also construct necessary conditions for the existence of a hypo structure with a fixed almost-contact form. For nonunimodular Lie algebras, we derive an obstruction to the existence of a hypo structure, with no choice involved. We apply these methods to classify solvable Lie algebras that admit a hypo structure.     

A branch-and-cut algorithm for the minimum-adjacency vertex coloring problem

In this work we study a particular way of dealing with interference in combinatorial optimization models representing wireless communication networks. In a typical wireless network, co-channel interference occurs whenever two overlapping antennas use the same frequency channel, and a less critical interference is generated whenever two overlapping antennas use adjacent channels. This motivates the formulation of the minimum-adjacency vertex coloring problem which, given an interference graph $G$ representing the potential interference between the antennas and a set of prespecified colors/channels, asks for a vertex coloring of $G$ minimizing the number of edges receiving adjacent colors. We propose an integer programming model for this problem and present three families of facet-inducing valid inequalities. Based on these results, we implement a branch-and-cut algorithm for this problem, and we provide promising computational results.