Characterizing a Histidine Switch Controlling pH-Dependent Conformational Changes of the Influenza Virus Hemagglutinin

AbstractDuring the fusion of the influenza virus to the host cell, bending of the HA2 chain of hemagglutinin into a hairpin-shaped structure in a pH-dependent manner facilitates the fusion of the viral envelope and the endosomal membrane. To characterize the structural and dynamical responses of the hinge region of HA2 to pH changes and examine the role of a conserved histidine in this region (the hinge histidine), we have performed an extensive set of molecular dynamics (MD) simulations of 26-residue peptides encompassing the hinge regions of several hemagglutinin subtypes under both neutral and low pH conditions, modeled by the change of the protonation state of the hinge histidine. More than 70 sets of MD simulations (collectively amounting to 25.1 μs) were performed in both implicit and explicit solvents to study the effect of histidine protonation on structural dynamics of the hinge region. In both explicit and implicit solvent simulations, hinge bending was consistently observed upon the protonation of the histidine in all the simulations starting with an initial straight helical conformation, whereas the systems with a neutral histidine retained their primarily straight conformation throughout the simulations. Conversely, the MD simulations starting from an initially bent conformation resulted in the formation of a straight helical structure upon the neutralization of the hinge histidine, whereas the bent structure was maintained when the hinge histidine remained protonated. Finally, mutation of the hinge histidine to alanine abolishes the bending response of the peptide altogether. A molecular mechanism based on the interaction of the hinge histidine with neighboring acidic residues is proposed to be responsible for its role in controlling the conformation of the hinge. We propose that this might present a common mechanism for pH-controlled structural changes in helical structures when histidines act as the pH sensor

Additive manufacturing of thin-walled SS316L-IN718 functionally graded materials by direct laser metal deposition

Functionally graded materials (FGMs) are a good response to those advanced applications that service requirements are diverse and require high performance. Additive manufacturing (AM) technology, with its many advantages, including high flexibility for complex geometries and near-net-shape integration, has attracted special attention in the development of FGMs. In this research, the solidification behavior and microstructure evolution in the laser additive manufacturing of thin-walled stainless steel 316L-Inconel 718 graded materials have been studied with the help of solidification concepts in the welding metallurgy, according to the common principles of welding and additive manufacturing processes. For this purpose, optical and electron microscopy techniques, X-ray energy dispersive spectroscopy, and microhardness measurement were used along the build direction of FGMs with different transition designs. Microstructure evaluation showed that due to re-melting of layers, despite the increased undercooling in the build direction, morphological evolution occasionally occurred periodically between solidification modes, and due to thermal accumulation, a coarser microstructure is formed in the final layers. In addition, in the chemical analysis, it was observed that the mixing of adjacent layers caused by dilution led to a deviation of the composition distribution from the desired design. Also, the microsegregation of some elements during the non-equilibrium solidification of the process caused secondary phases such as carbides and intermetallic compound of Laves, which can have an adverse effect on the mechanical properties of the structure. However, microhardness variations along the cross-section of the samples showed that the gradation of the dissimilar thin-walled structure can effectively bring the properties and behavior of adjacent layers closer together and therefore be very useful in improving the service life

The Reported Activities and Beliefs of the Students Preparing for the Specialised English Test (SPE).

The purpose of this study is to explore the 'washback effect' of a high stakes test known as the Specialised English Test (SPE) which is used to admit English-major applicants into English departments at universities in Iran. A belief commonly held about the SPE Test is that students admitted to university since its introduction in 2002 have been more proficient and successful than pre-2002 students. However, no research has been done on how the test might be affecting the learning of the students. I examined the reported learning activities of the students to see what they reported they did in order to prepare for the test and why. As the SPE test preparation is done partly independently (by out-of-school resources), I also considered the students' reported learning beliefs to examine how the test was interacting with those criteria. Thus, reported activities and learning beliefs were the main themes of this study. I collected the data from two contrasting groups- students who were going to take the SPE Test and students who were going to take the GE Test. I used three instruments to collect the data: questionnaire, letters, and interviews. 1038 students responded to the questionnaire, 91 students wrote the letters, and 18 students were interviewed. The results showed that the SPE Test did have washback in the areas where washback was intended. The study also identified factors other than the test which influenced the learners. As regards learning beliefs, the results showed that the test preparation activities of the students were both affecting them as well as were affected by them. The study suggested that in addition to test innovations, the beliefs of the learners should also be taken into account in order to promote positive washback. The study also recommended the use of letters as an instrument in washback studies provided they are written by interested students and the results are followed up by other instruments such as interviews

Hypotensive medicinal plants according to ethnobotanical evidence of Iran: A systematic review

Hypertension is called the silent killer because it leads finally to death silently and asymptomatically. If hypertension is not controlled at early stages, it disturbs the functions of cardiovascular system and other organs of the body. The aim of this review article is to report the medicinal plants used to treat hypertension in traditional medicine according to ethnobotanical evidence of different regions of Iran. This helps to offer different medicinal plants used to treat hypertension in these regions in a systematic manner, and approaches and keys to discover effective substances and develop new herbal drugs to researchers as well as to inform them of folk knowledge about using medicinal plants to prevent hypertension. In this article, 47 medicinal plants from 17 different regions in Iran were reported to be used to lower blood pressure. These plants can be investigated in animal studies and clinical trials to be used in developing herbal drugs for prevention and treatment of hypertension. © 2016, Sphinx Knowledge House. All rights reserved