Experimental Vaccines for Prevention of Marburg Hemorrhagic Fever and Animal Models for Studying Pathogenesis

Marburg fever is an acute natural-focal disease characterized by severe course, hemorrhagic syndrome, high level of contagiousness and lethality. The causative agent of the disease is the RNA-containing virus belonging to the family of filoviruses (Filoviridae). The main problem faced by doctors and scientists involved in the fight against Marburg fever is the lack of vaccines and preventive drugs against this disease. The development of effective vaccines against filovirus infection is relevant for protecting the population living in natural foci and medical personnel during epidemic outbreaks, as well as for ensuring safe research work in BSL-4 laboratories. In this regard, this review considers biomodels suitable for studying the pathogenesis of filovirus infections, preclinical studies of specific activity and harmlessness of prototype Marburg virus vaccines and variants of these vaccines

Supplementary material for the article: Milenković, M.; Shcherbakov, I. N.; Popov, L. D.; Levchenkov, S. I.; Borodkin, S. A.; Alexandrov, G. G. Synthesis, Characterization and Crystal Structures of Ni(II) and Cu(I) Complexes with the Condensation Product of 2-(Diphenylphosphino)Benzaldehyde and 1-Hydrazinophthalazine. Polyhedron 2017, 121, 278–284. https://doi.org/10.1016/j.poly.2016.10.020

Supplementary material for: [https://doi.org/10.1016/j.poly.2016.10.020]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2368]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3256

Light-emitting-diode Fourier-transform spectroscopy of HD16O between 11200 and 12400 cm-1

The absorption spectrum of monodeuterated water, HDO has been investigated between 11200 and 12400 cm-1. The spectrum has been recorded using IFS-125M interferometer with spectral resolution of 0.05 cm-1. For measurements White’s-type cell were used. The bright light emitting diode (LED) EDEI-1LS3-R was applied as a source of radiation. Signal to noise ratio was about 104. The spectral line parameters - line positions, intensities and half-widths were obtained by least square fitting. As a result of the spectrum analysis the line list containing more than 1500 lines was created. The spectral line parameters have been compared with the previous measured and calculated data. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Volcano–Plutonic Complex of the Tumrok Range (Eastern Kamchatka): An Example of the Ural-Alaskan Type Intrusion and Related Volcanic Series

Zoned plutons, composed of dunites, pyroxenites, and gabbroic rocks, have been referred to as the Ural-Alaskan type complexes (UA-complexes) and occur in numerous paleo-arc settings worldwide. Many of these complexes are source rocks for economic placers of platinum-group metals. Thus, it is important to understand how UA-complexes form and the origin and behavior of platinum-group elements (PGEs). It is widely assumed that the UA-complexes result from differentiation of supra-subduction high-Ca high-Mg sub-alkaline magmas. However, there is a lack of direct evidence for the existence and differentiation of such magmas, mainly because cases of UA-complexes being spatially and temporally linked to co-genetic volcanics are unknown. We studied an UA-complex from the Tumrok range (Eastern Kamchatka) where a dunite-clinopyroxenite-gabbro assemblage is spatially and temporary related to high-Ca volcanics (i.e., picrites and basalts). Based on the mineral and chemical composition of the rocks, mineral chemistry, and composition of melt inclusions hosted within rock-forming minerals, we conclude that the intrusive assemblage and the volcanics are co-genetic and share the same parental magma of ankaramitic composition. Furthermore, the compositions of the plutonic rocks are typical of UA-complexes worldwide. Finally, the rocks studied exhibit a full differentiation sequence from olivine-only liquidus in picrites and dunites to eutectic crystallization of diopside or hornblende, plagioclase, and K-Na feldspar in plagio-wehrlites and gabbroic rocks. All these results make the considered volcano–plutonic complex a promising case for petrological studies and modelling of UA-complex formation

LED-based Fourier transform spectroscopy of H216O in the range 15500-16000 cm-1

The vibrational-rotational absorption spectrum of water vapor within the range 15500–16000 cm−1 is measured and analyzed. The spectrum is recoded with an IFS-125M Fourier transform spectrometer with a resolution of 0.03 cm−1, at pressure of 25 mbar, at a temperature of 24°C, and at an optical path length of 34.8 m. The measurements are performed using a multipass White cell with a base length of 60 cm. A light-emitting diode is used as a radiation source. The signal-to-noise ratio is about 104, which makes it possible to measure the parameters of lines with intensities on the order of 10−27 cm/molecule. The centers, intensities, and half-widths of lines are determined by fitting the Voigt profile parameters to measured data set by the least squares method. A list of more than 430 lines is formed based on the analysis of the spectrum. The obtained results are compared with calculated and experimental data of other authors

The effect of thioredoxin and prochymosin coexpression on the refolding of recombinant alpaca chymosin

The milk-clotting enzyme chymosin is a member of the group of aspartate proteinases. Chymosin is the main component of rennet traditionally obtained from the stomachs of dairy calves and widely used to coagulate milk in the production of various types of cheese. Another source of chymosin, which does not require the killing of animals, is based on recombinant DNA technology. Recombinant alpaca chymosin has a number of valuable technological properties that make it attractive for use in cheese-making as an alternative to recombinant bovine chymosin. The purpose of this work is to study the effect of coexpression of thioredoxin and prochymosin on the refolding of the recombinant zymogen and the activity of alpaca chymosin. To achieve this goal, on the basis of the pET32a plasmid, an expression vector was constructed containing the thioredoxin A gene fused to the N-terminal sequence of the marker enzyme zymogen, alpaca prochymosin. Using the constructed vector, pETTrxProChn, a strain-producer of the recombinant chimeric protein thioredoxin-prochymosin was obtained. The choice of prochymosin as a model protein is due to the ability of autocatalytic activation of this zymogen, in which the pro-fragment is removed, together with the thioredoxin sequence attached to it, with the formation of active chymosin. It is shown that Escherichia coli strain BL21 transformed with the pET-TrxProChn plasmid provides an efficient synthesis of the thioredoxin-prochymosin chimeric molecule. However, the chimeric protein accumulates in inclusion bodies in an insoluble form. Therefore, a renaturation procedure was used to obtain the active target enzyme. Fusion of thioredoxin capable of disulfide-reductase activity to the N-terminal sequence of prochymosin provides optimal conditions for zymogen refolding and increases the yield of recombinant alpaca chymosin immediately after activation and during long-term storage by 13 and 15 %, respectively. The inclusion of thioredoxin in the composition of the chimeric protein, apparently, contributes to the process of correct reduction of disulfide bonds in the prochymosin molecule, which is reflected in the dynamics of the increase in the milk-clotting activity of alpaca chymosin during long-term storage

From colloidal CdSe quantum dots to microscale optically anisotropic supercrystals through bottom-up self-assembly

This is the author accepted manuscript. The final version is available on open access from Royal Society of Chemistry via the DOI in this recordThe development of fabrication techniques for novel nanostructured materials is one of the key tasks of modern materials science. One pathway to successfully complete this task is the bottom-up assembly of colloidal nanoparticles into ordered superstructures, possessing both the properties of individual nanoparticles and further novel properties resulting from their interactions. However, nanoparticle self-assembly depends on a variety of parameters, which makes the precise control of this process a complicated problem. Here, the time course of quantum dot (QD) self-assembly into ordered superstructures has been analyzed, along with the evolution of their morphological and optical properties. QD self-assembly occurs through two distinct stages (homo- and hetero-geneous), leading to the formation of supercrystals with a layered morphology. Analysis of the optical properties throughout the superstructures’ growth has shown that the absorption and photoluminescence (PL) bands are blue shifted, retaining almost the same PL lifetimes as in the initial QD solution. The supercrystals formed possess a further unique optical property caused by their layered morphology; namely, a four-fold symmetry characterized by strong birefringence. Such supercrystals may be used for the fabrication of microscale optical paths with high extinction coefficients and specific polarization properties for novel optoelectronic devices.This study was supported by the Ministry of Education and Science of the Russian Federation through the grant No. 14.584.21.0032 (ID RFMEFI58417X0032), the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom via the EPSRC Centre for Doctoral Training in Electromagnetic Metamaterials (Grant No. EP/L015331/1) and via EP/N035569/1, and the Royal Society via International Exchange Grant No. 2016/R1

Model systems of human immunodef iciency virus (HIV-1) for in vitro eff icacy assessment of candidate vaccines and drugs against HIV-1

HIV infection still remains a major challenge for healthcare systems of the world. There are several aspects on counteracting the HIV/AIDS epidemic. The f irst aspect covers preventive measures including educational campaigns on HIV/AIDS and promotion of a healthy lifestyle, protected sex, and pre-exposure prophylaxis of vulnerable groups. The second aspect is timely HIV testing and the use of antiretroviral therapy when test results come back positive. The third aspect is the scientif ic research associated with discovering new pharmaceutical agents and developing HIV-1 vaccines. Selecting an adequate tool for quick and accurate in vitro eff icacy assessment is the key aspect for eff icacy assessment of vaccines and chemotherapy drugs. The classical method of virology, which makes it possible to evaluate the neutralizing activity of the sera of animals immunized with experimental vaccines and the eff icacy of chemotherapy agents is the method of neutralization using viral isolates and infectious molecular clones, i. e. infectious viral particles obtained via cell transfection with a plasmid vector including the full-length HIV-1 genome coding structural, regulatory, and accessory proteins of the virus required for the cultivation of replication-competent viral particles in cell culture. However, neutralization assessment using viral isolates and infectious molecular clones is demanding in terms of time, effort, and biosafety measures. An alternative eliminating these disadvantages and allowing for rapid screening is the use of pseudoviruses, which are recombinant viral particles, for the analysis of neutralizing activity. Pseudotyped viruses have defective genomes restricting their replication to a single cycle, which renders them harmless compared to infectious viruses. The present review focuses on describing viral model systems for in vitro eff icacy assessment of vaccines and drugs against HIV-1, which include primary HIV-1 isolates, laboratoryadapted strains, infectious molecular clones, and env-pseudoviruses. A brief comparison of the listed models is presented. The HIV-1 env-pseudoviruses approach is described in more detail

ESOPHAGEAL INJURY CAUSED BY THE SPINE DEFORMITY CORRECTION USING VARIOUS TECHNIQUES OF SPINAL FIXATION

Objectives - to improve the surgical treatment results in patients with injuries of the esophagus after the elimination of deformation of a vertebral column with metal devices. Material and methods. From 2001 to 2018 we treated 17 patients with esophageal injury appeared as a result of cervical vertebras fixation with metal devices - in 12 patients to correct their instability due to the traumatic compression fractures and in 5 patients having the herniated discs with the spinal channel compression. 12 patients underwent the urgent operation, 5 patients - the delayed or planned one. Three mechanisms of esophageal injury were defined: 5 patients had the first type of injury, 8 - the second type, 4 - the third type. The patients were operated on after the diagnosis confirmation. The operation was aimed at the removal of the metal device from the collum and the closure of the esophagus wall defect. Tactics of treatment of the esophageal injuries depended on the alterations in its paries, the size of the defect, the nature of the trauma and the mediastinitis prevalence. In 8 patients the primary suture of the esophagus was applied. In 9 patients with decubituses of the esophagus and the large size of the defect we applied the partial suturing of the defect and the transesophageal drainage of the fistula and mediastinum, strengthening the injured zone with a muscle on the pedicle. Results. First intention healing was achieved in 5 patients of the 8 ones who underwent the esophagus wall suturing without a fistula transesophageal drainage. The partial suture incompetence occurred in 3 cases and it required the transesophageal drainage through the defect in the esophagus wall. The external tubular esophageal fistula formed in 12 patients. After the drainage removal the fistula closed in 10 cases. One of the 17 patients died of the multiple organ failure and sepsis. Conclusion. Injuries of the esophagus caused by the metal devices fixing the unstable vertebras have the clinical features depending on the installation time. The suturing of the esophageal defect and the suture strengthening m. sternocleidomastoideus on the pedicle supplemented by a through lumenal transesophageal drainage have advantage in comparison with the esophageal wall suturing without drainage