Discovery of Leptulipin,a New Anticancer Protein from theIranian Scorpion,Hemiscorpius lepturus

Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from Hemiscorpius lepturus scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in BCL-2 expression and an increase in Bax and Caspase 9 genes. In this study, we discovered a new anticancer protein from H. lepturus scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.     

The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms

Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 Å resolution, as well as a model of the full-length luminal protein obtained by a combination of macromolecular crystallography and targeted cross-linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS-epi1, involving a His/double-Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal-coordinating center and pattern of N-glycosylation of the protein. Additionally, the structure of DS-epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS-epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitors.     

Deterministic global derivative-free optimization of black-box problems with bounded Hessian

Obtaining guaranteed lower bounds for problems with unknown algebraic form has been a major challenge in derivative-free optimization. In this work, we pre     

In silico identification and in vitro antiviral validation of potential inhibitors against Chikungunya virus

Journal of Computer-Aided Molecular Design - The Chikungunya virus (CHIKV) has become endemic in the Africa, Asia and Indian subcontinent, with its continuous re-emergence causing a significant...     

Efficient and green catalytic system incorporating new benzimidazolium salts for the Sonogashira cross‐coupling reaction

A number of novel benzimidazole salts were synthesized and their structures were determined using ¹H NMR, ¹³C NMR and infrared spectroscopic techniques and elemental analysis. A catalyst system consisting of Pd(OAc)₂ and copper nanoparticles in the presence of Cs₂CO₃ and incorporating the novel benzimidazole salts in poly(ethylene glycol) solvent significantly improved the yields of Sonogashira reactions between aryl halides and phenylacetylene under microwave irradiation in 10 min.     

Preparation of produced water reference material for analyzing 226Ra by gamma spectrometry

Journal of Radioanalytical and Nuclear Chemistry - Produced water reference material containing high concentration of 226Ra activity was prepared in 2009 and used for ALMERA worldwide proficiency...     

Comparison of Li+‐ion conductivity in linear and crosslinked poly(ethylene oxide)

Polymer electrolytes are of tremendous importance for applications in modern lithium‐ion (Li⁺‐ion) batteries due to their satisfactory ion conductivity, low toxicity, reduced flammability, as well as good mechanical and thermal stability. In this study, the Li⁺‐ion conductivity of well‐defined poly(ethylene oxide) (PEO) networks synthesized via copper(I)‐catalyzed azide–alkyne cycloaddition is investigated by electrochemical impedance spectroscopy after addition of different lithium salts. The ion conductivity of the network electrolytes increases with increasing molar mass of the PEO chains between the junction points which is completely opposite to the behavior of their respective uncrosslinked linear precursors. Obviously, this effect is directly related to the segmental mobility of the PEO chains. Furthermore, the ion conductivity of the network electrolytes under investigation increases also with increasing size of the anion of the added lithium salt due to a weaker anti‐plasticizing effect of the more bulky anions. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 21–28     

Effect of prior austenite grain size on the formation of carbide-free bainite in low-alloy steel

ABSTRACT

Inconsistencies exist in literature regarding the effect of prior austenite grain size (PAGS) on the extent and kinetics of bainite transformation. Attempts have been made in the present work to address these issues in a low-alloy carbide-free bainitic steel using dilatometry, over a range of PAGS. The bainite transformation kinetics in the above-mentioned conditions have been analysed quantitatively using established kinetic model to extract information related to the transformation mechanisms in such conditions. Greater obstruction from grain boundaries in fine-grained austenite restricts sheaves of bainite to develop completely and thereby reduces the volume fraction of bainite in comparison with coarse-grained austenite. Initial nucleation rate of bainite transformation increases with decreasing PAGS due to an increase in the nucleation site density. However, the maximum nucleation rate decreases consistently with decreasing PAGS due to gradual reduction in the autocatalytic factor.