The Effect of Nonelectrolyte Additives with Hydrophilic and Hydrophobic Hydration on the Growth of KDP Crystals from Aqueous Solutions

Crystallography Reports - The effect of nonelectrolyte additives with hydrophilic and hydrophobic hydration on the growth of potassium dihydrogen phosphate (KH2PO) crystals in the kinetic mode at...     

Monte Carlo Study of Slot-waveguide Liquid Crystal Phase Shifters

Abstract

We present detailed Monte Carlo simulations of a simple model of a nematic liquid crystal slot waveguide shifter, investigating the effect of an applied electric external field. The simulations are based on the Lebwohl-Lasher lattice spin model with boundary conditions chosen to mimic the planar alignment as in Silicon Organic Hybrid waveguides and the homeotropic anchoring appropriate for Polydimethylsiloxane polymer walls. The external field is modeled by adding a term to the Hamiltonian which describes its coupling to the mesogenic molecules. We have investigated the effect of the external field on the optical transmission and the ordering across the cell.     

Vibration and deflection analysis of thin cracked and submerged orthotropic plate under thermal environment using strain gradient theory

Nonlinear Dynamics - Based on a non-classical plate theory, a nonlinear analytical model is proposed to analyze transverse vibration of thin partially cracked and submerged orthotropic plate in the...     

Recognition of Dimethylarginine Analogues by Tandem Tudor Domain Protein Spindlin1

Epigenetic readout of the combinatorial posttranslational modification comprised of trimethyllysine and asymmetric dimethylarginine (H3K4me3R8me2a) takes place via biomolecular recognition of tandem Tudor-domain-containing protein Spindlin1. Through comparative thermodynamic data and molecular dynamics simulations, we sought to explore the binding scope of asymmetric dimethylarginine mimics by Spindlin1. Herein, we provide evidence that the biomolecular recognition of H3K4me2R8me2a is not significantly affected when R8me2a is replaced by dimethylarginine analogues, implying that the binding of K4me3 provides the major binding contribution. High-energy water molecules inside both aromatic cages of the ligand binding sites contribute to the reader–histone association upon displacement by histone peptide, with the K4me3 hydration site being lower in free energy due to a flip of Trp151.     

Comparison of Proton Acceptor and Proton Donor Properties of H2O and H2O2 in Organic Crystals of Drug-like Compounds: Peroxosolvates vs. Crystallohydrates

Two new peroxosolvates of drug-like compounds were synthesized and studied by a combination of X-ray crystallographic, Raman spectroscopic methods, and periodic DFT computations. The enthalpies of H-bonds formed by hydrogen peroxide (H₂O₂) as a donor and an acceptor of protons were compared with the enthalpies of analogous H-bonds formed by water (H₂O) in isomorphic (isostructural) hydrates. The enthalpies of H-bonds formed by H₂O₂ as a proton donor turned out to be higher than the values of the corresponding H-bonds formed by H₂O. In the case of H₂O₂ as a proton acceptor in H-bonds, the ratio appeared reversed. The neutral O∙∙∙H-O/O∙∙∙H-N bonds formed by the lone electron pair of the oxygen atom of water were the strongest H-bonds in the considered crystals. In the paper, it was found out that the low-frequency Raman spectra of isomorphous crystalline hydrate and peroxosolvate of N-(5-Nitro-2-furfurylidene)-1-aminohydantoin are similar. As for the isostructural hydrate and peroxosolvate of the salt of protonated 2-amino-nicotinic acid and maleic acid monoanion, the Raman spectra are different.     

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.     

Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

We here outline the importance of open-source, accessible tools for computer-aided drug discovery (CADD). We begin with a discussion of drug discovery in general to provide context for a subsequent discussion of structure-based CADD applied to small-molecule ligand discovery. Next, we identify usability challenges common to many open-source CADD tools. To address these challenges, we propose a browser-based approach to CADD tool deployment in which CADD calculations run in modern web browsers on users’ local computers. The browser app approach eliminates the need for user-initiated download and installation, ensures broad operating system compatibility, enables easy updates, and provides a user-friendly graphical user interface. Unlike server apps—which run calculations “in the cloud” rather than on users’ local computers—browser apps do not require users to upload proprietary information to a third-party (remote) server. They also eliminate the need for the difficult-to-maintain computer infrastructure required to run user-initiated calculations remotely. We conclude by describing some CADD browser apps developed in our lab, which illustrate the utility of this approach. Aside from introducing readers to these specific tools, we are hopeful that this review highlights the need for additional browser-compatible, user-friendly CADD software.     

Chemometric Analysis of Urinary Volatile Organic Compounds to Monitor the Efficacy of Pitavastatin Treatments on Mammary Tumor Progression over Time

Volatile organic compounds (VOCs) in urine are potential biomarkers of breast cancer. Previously, our group has investigated breast cancer through analysis of VOCs in mouse urine and identified a panel of VOCs with the ability to monitor tumor progression. However, an unanswered question is whether VOCs can be exploited similarly to monitor the efficacy of antitumor treatments over time. Herein, subsets of tumor-bearing mice were treated with pitavastatin at high (8 mg/kg) and low (4 mg/kg) concentrations, and urine was analyzed through solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS). Previous investigations using X-ray and micro-CT analysis indicated pitavastatin administered at 8 mg/kg had a protective effect against mammary tumors, whereas 4 mg/kg treatments did not inhibit tumor-induced damage. VOCs from mice treated with pitavastatin were compared to the previously analyzed healthy controls and tumor-bearing mice using chemometric analyses, which revealed that mice treated with pitavastatin at high concentrations were significantly different than tumor-bearing untreated mice in the direction of healthy controls. Mice treated with low concentrations demonstrated significant differences relative to healthy controls and were reflective of tumor-bearing untreated mice. These results show that urinary VOCs can accurately and noninvasively predict the efficacy of pitavastatin treatments over time.     

The Effects of Charged Amino Acid Side-Chain Length on Diagonal Cross-Strand Interactions between Carboxylate- and Ammonium-Containing Residues in a β-Hairpin

The β-sheet is one of the common protein secondary structures, and the aberrant aggregation of β-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of β-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a β-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (−0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing β-sheet containing molecular entities for various applications.