Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review.publishersversionPeer reviewe

Prokaryotic expression, purification and immunogenicity in rabbits of the small antigen of hepatitis delta virus

Funding Information: Expression and purification of HDV antigen was supported by Russian Foundation for Basic Research (grant 16-04-01490a). Evaluation of serum by Western blot and confocal microscopy was supported by Russian Science Foundation (grant 14-14-01021). Experiments in rabbits were supported by the Swedish Institute grants 09272_2013 and 19806_2016. Cross-border collaboration of the partners, exchange of the materials and standard operation procedures used in the study, and dissemination of the data were supported by the EU Twinning project VACTRAIN, contract nr 692293. Publisher Copyright: © 2016 by the authors; licensee MDPI, Basel, Switzerland.Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B virus infection in 5% patients. HDV has been studied for four decades; however, the knowledge on its life-cycle and pathogenesis is still sparse. The studies are hampered by the absence of the commercially-available HDV-specific antibodies. Here, we describe a set of reproducible methods for the expression in E. coli of His-tagged small antigen of HDV (S-HDAg), its purification, and production of polyclonal anti-S-HDAg antibodies in rabbits. S-HDAg was cloned into a commercial vector guiding expression of the recombinant proteins with the C-terminal His-tag. We optimized S-HDAg protein purification procedure circumventing a low affinity of the His-tagged S-HDAg to the Ni-nitrilotriacetyl agarose (Ni-NTA-agarose) resin. Optimization allowed us to obtain S-HDAg with >90% purity. S-HDAg was used to immunize Shinchilla grey rabbits which received 80 µg of S-HDAg in two subcutaneous primes in the complete, followed by four 40 µg boosts in incomplete Freunds adjuvant. Rabbits were bled two weeks post each boost. Antibody titers determined by indirect ELISA exceeded 107. Anti-S-HDAg antibodies detected the antigen on Western blots in the amounts of up-to 100 pg. They were also successfully used to characterize the expression of S-HDAg in the eukaryotic cells by immunofluorescent staining/confocal microscopy.publishersversionPeer reviewe

Historical, theoretical and methodological issues of special pedagogy

The purpose of the article is to present the scientific views of one of the leading special pedagogues of our country, whose work over the past decades has been devoted to the history of special pedagogy and its theoretical and methodological foundations - N. M. Na¬zarova. Her work is characterized by a wealth of ideas, diversity and wide cov-erage of the problems of teaching and raising children with special educational needs, so the article does not purport to be comprehensively complete while describing the theoretical positions of the scholar.В статье представлены научные взгляды Н. М. Назаровой, одного из ведущих специальных педагогов нашей страны

The optical identifcation of events with poorly defined locations: The case of the Fermi GBM GRB140801A

We report the early discovery of the optical afterglow of gamma-ray burst (GRB) 140801A in the 137 deg$^2$ 3-$\sigma$ error-box of the Fermi Gamma-ray Burst Monitor (GBM). MASTER is the only observatory that automatically react to all Fermi alerts. GRB 140801A is one of the few GRBs whose optical counterpart was discovered solely from its GBM localization. The optical afterglow of GRB 140801A was found by MASTER Global Robotic Net 53 sec after receiving the alert, making it the fastest optical detection of a GRB from a GBM error-box. Spectroscopy obtained with the 10.4-m Gran Telescopio Canarias and the 6-m BTA of SAO RAS reveals a redshift of $z=1.32$. We performed optical and near-infrared photometry of GRB 140801A using different telescopes with apertures ranging from 0.4-m to 10.4-m. GRB 140801A is a typical burst in many ways. The rest-frame bolometric isotropic energy release and peak energy of the burst is $E_\mathrm{iso} = 5.54_{-0.24}^{+0.26} \times 10^{52}$ erg and $E_\mathrm{p, rest}\simeq280$ keV, respectively, which is consistent with the Amati relation. The absence of a jet break in the optical light curve provides a lower limit on the half-opening angle of the jet $\theta=6.1$ deg. The observed $E_\mathrm{peak}$ is consistent with the limit derived from the Ghirlanda relation. The joint Fermi GBM and Konus-Wind analysis shows that GRB 140801A could belong to the class of intermediate duration. The rapid detection of the optical counterpart of GRB 140801A is especially important regarding the upcoming experiments with large coordinate error-box areas.Comment: in press MNRAS, 201

Gravitational stability and dynamical overheating of stellar disks of galaxies

We use the marginal stability condition for galactic disks and the stellar velocity dispersion data published by different authors to place upper limits on the disk local surface density at two radial scalelengths $R=2h$. Extrapolating these estimates, we constrain the total mass of the disks and compare these estimates to those based on the photometry and color of stellar populations. The comparison reveals that the stellar disks of most of spiral galaxies in our sample cannot be substantially overheated and are therefore unlikely to have experienced a significant merging event in their history. The same conclusion applies to some, but not all of the S0 galaxies we consider. However, a substantial part of the early type galaxies do show the stellar velocity dispersion well in excess of the gravitational stability threshold suggesting a major merger event in the past. We find dynamically overheated disks among both seemingly isolated galaxies and those forming pairs. The ratio of the marginal stability disk mass estimate to the total galaxy mass within four radial scalelengths remains within a range of 0.4---0.8. We see no evidence for a noticeable running of this ratio with either the morphological type or color index.Comment: 25 pages, 5 figures, accepted to Astronomy Letter

Changes in Phospholipid Composition Studied by HPLC and Electric Properties of Liver Cell Membrane of Ethanol-Poisoned Rats

Ethanol introduced into the organism undergoes rapid metabolism to acetaldehyde and then to acetic acid. The process is accompanied by formation of reactive oxygen species (ROS), which damage mainly lipids of membrane cells. The effects of ROS can be neutralized by administering preparations with antioxidant properties. The natural preparations of this kind are teas

Long-term multiwavelength monitoring and reverberation mapping of NGC 2617 during a changing-look event

We present the results of photometric and spectroscopic monitoring campaigns of the changing look AGN NGC~2617 carried out from 2016 until 2022 and covering the wavelength range from the X-ray to the near-IR. The facilities included the telescopes of the SAI MSU, MASTER Global Robotic Net, the 2.3-m WIRO telescope, Swift, and others. We found significant variability at all wavelengths and, specifically, in the intensities and profiles of the broad Balmer lines. We measured time delays of ~ 6 days (~ 8 days) in the responses of the H-beta (H-alpha) line to continuum variations. We found the X-ray variations to correlate well with the UV and optical (with a small time delay of a few days for longer wavelengths). The K-band lagged the B band by 14 +- 4 days during the last 3 seasons, which is significantly shorter than the delays reported previously by the 2016 and 2017--2019 campaigns. Near-IR variability arises from two different emission regions: the outer part of the accretion disc and a more distant dust component. The HK-band variability is governed primarily by dust. The Balmer decrement of the broad-line components is inversely correlated with the UV flux. The change of the object's type, from Sy1 to Sy1.8, was recorded over a period of ~ 8 years. We interpret these changes as a combination of two factors: changes in the accretion rate and dust recovery along the line of sight.Comment: 14 pages, 15 figures, accepted by the MNRA

Human GLI3 Intragenic Conserved Non-Coding Sequences Are Tissue-Specific Enhancers

The zinc-finger transcription factor GLI3 is a key regulator of development, acting as a primary transducer of Sonic hedgehog (SHH) signaling in a combinatorial context dependent fashion controlling multiple patterning steps in different tissues/organs. A tight temporal and spatial control of gene expression is indispensable, however, cis-acting sequence elements regulating GLI3 expression have not yet been reported. We show that 11 ancient genomic DNA signatures, conserved from the pufferfish Takifugu (Fugu) rubripes to man, are distributed throughout the introns of human GLI3. They map within larger conserved non-coding elements (CNEs) that are found in the tetrapod lineage. Full length CNEs transiently transfected into human cell cultures acted as cell type specific enhancers of gene transcription. The regulatory potential of these elements is conserved and was exploited to direct tissue specific expression of a reporter gene in zebrafish embryos. Assays of deletion constructs revealed that the human-Fugu conserved sequences within the GLI3 intronic CNEs were essential but not sufficient for full-scale transcriptional activation. The enhancer activity of the CNEs is determined by a combinatorial effect of a core sequence conserved between human and teleosts (Fugu) and flanking tetrapod-specific sequences, suggesting that successive clustering of sequences with regulatory potential around an ancient, highly conserved nucleus might be a possible mechanism for the evolution of cis-acting regulatory elements