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Acta Naturae

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https://www.readbyqxmd.com/read/28461981/antiretroviral-activity-of-a-novel-pyrimidyl-di-diazaspiroalkane-derivative
#1
E A Novoselova, O B Riabova, I A Leneva, V G Nesterenko, R N Bolgarin, V A Makarov
A novel compound, 3,3'-(5-nitropyrimidine-4,6-diyl)bis-3,12-diaza-6,9-diazoniadispiro[5.2.5.2]hexadecane tetrachloride dihydrochloride, was synthesized. The compound was found to inhibit the replication of various viral families by blocking specific heparan sulfate receptors on the host cell's surface. In experiments, the compound was found to be highly effective against several strains of HIV retroviruses.
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461980/mapping-the-d-melanogaster-en1a-enhancer-modules-responsible-for-transcription-activation-and-long-distance-enhancer-promoter-interactions
#2
L S Melnikova, E A Pomerantseva, V V Molodina, P G Georgiev
The structure of the new enhancer En1A of the 1A region of the X chromosome of D. melanogaster was investigated. Two distinct regulatory elements were found. The first element is responsible for transcription activation, and the second element provides specific interaction with the promoter of the yellow gene. The findings support the hypothesis of a modular structure for enhancers, including certain sequences that bind transcription activators and special communication elements providing long-distance enhancer-promoter interaction...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461979/search-for-modified-dna-sites-with-the-human-methyl-cpg-binding-enzyme-mbd4
#3
D A Yakovlev, A A Kuznetsova, O S Fedorova, N A Kuznetsov
The MBD4 enzyme initiates the process of DNA demethylation by the excision of modified DNA bases, resulting in the formation of apurinic/apyrimidinic sites. MBD4 contains a methyl-CpG-binding domain which provides the localization of the enzyme at the CpG sites, and a DNA glycosylase domain that is responsible for the catalytic activity. The aim of this work was to clarify the mechanisms of specific site recognition and formation of catalytically active complexes between model DNA substrates and the catalytic N-glycosylase domain MBD4cat...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461978/dual-active-site-in-the-endolytic-transglycosylase-gp144-of-bacteriophage-phikz
#4
O V Chertkov, G A Armeev, I V Uporov, S A Legotsky, N N Sykilinda, A K Shaytan, N L Klyachko, K A Miroshnikov
Lytic transglycosylases are abundant peptidoglycan lysing enzymes that degrade the heteropolymers of bacterial cell walls in metabolic processes or in the course of a bacteriophage infection. The conventional catalytic mechanism of transglycosylases involves only the Glu or Asp residue. Endolysin gp144 of Pseudomonas aeruginosa bacteriophage phiKZ belongs to the family of Gram-negative transglycosylases with a modular composition and C-terminal location of the catalytic domain. Glu115 of gp144 performs the predicted role of a catalytic residue...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461977/voltage-dependent-interaction-of-capsaicine-and-protons-on-trpv1-receptors
#5
E A Tsvetkov, N N Potatieva, K V Bolshakov
The interaction of TRPV1-receptors agonists (capsaicin and protons) has been studied on cultured CHO cells transfected by TRPV1-receptors. Using the whole-cell patch-clamp approach, it was shown that summation of the currents induced by agonist application was dependent on the membrane potential. The TRPV1-mediated currents induced by the pH and Capsaicin demonstrated arithmetical summation at potentials between 40--40 mV, while they were potentiated at potentials below -40 mV. Currents induced by the pH and Capsaicin combined were higher in comparison with the arithmetic sum of the currents induced by the pH and Capsaicin applied separately at such potentials...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461976/differentiation-of-human-pluripotent-stem-cells-into-mesodermal-and-ectodermal-derivatives-is-independent-of-the-type-of-isogenic-reprogrammed-somatic-cells
#6
E S Philonenko, M V Shutova, E A Khomyakova, E M Vassina, O S Lebedeva, S L Kiselev, M A Lagarkova
Induced pluripotent stem cells (iPSCs) have the capacity to unlimitedly proliferate and differentiate into all types of somatic cells. This capacity makes them a valuable source of cells for research and clinical use. However, the type of cells to be reprogrammed, the selection of clones, and the various genetic manipulations during reprogramming may have an impact both on the properties of iPSCs and their differentiated derivatives. To assess this influence, we used isogenic lines of iPSCs obtained by reprogramming of three types of somatic cells differentiated from human embryonic stem cells...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461975/intratumoral-morphological-heterogeneity-of-breast-cancer-as-an-indicator-of-the-metastatic-potential-and-tumor-chemosensitivity
#7
T S Gerashchenko, M V Zavyalova, E V Denisov, N V Krakhmal, D N Pautova, N V Litviakov, S V Vtorushin, N V Cherdyntseva, V M Perelmuter
Breast cancer (BC) demonstrates considerable intratumoral morphological heterogeneity. The aim of this work was to evaluate the relationship among different morphological structures, the rate of metastasis, and efficacy of neoadjuvant chemotherapy (NAC) in NAC-treated (n = 427) and NAC-naïve (n = 249) BC patients. We also studied the involvement of an epithelial-mesenchymal transition (EMT) in the development of the intratumoral morphological heterogeneity of BC. We found a significant association between the intratumoral morphological heterogeneity and the rate of BC metastasis and response to NAC, which, in most cases, correlated with the presence of alveolar and trabecular structures...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461974/prolyl-glycyl-proline-pgp-peptide-prevents-an-increase-in-vascular-permeability-in-inflammation
#8
N S Bondarenko, A N Shneiderman, A A Guseva, B A Umarova
This study was aimed at investigating the effect of prolyl-glycyl-proline (PGP) tripeptide on vascular permeability in rats with an inflammation. It was found that the peptide reduces the rat paw edema induced by a subcutaneous administration of histamine to the same extent as the conventional anti-inflammatory agent diclofenac. However, an assessment of the relative expression level of the cox-2 gene at the inflammation focus using real-time PCR showed that, in contrast to diclofenac, PGP does not affect the cox-2 gene expression...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461973/building-a-full-atom-model-of-l-dtranspeptidase-2-from-mycobacterium-tuberculosis-for-screening-new-inhibitors
#9
S M Baldin, N M Misiura, V K Švedas
L,D-transpeptidase 2 from Mycobacterium tuberculosis plays a key role in the formation of the cell wall of a pathogen and catalyzes the cross-linking of growing peptidoglycan chains by non-classical 3-3 bonds, which causes resistance to a broad spectrum of penicillins. Molecular modeling of enzyme interactions with the N- and C-terminal tetrapeptide fragments of growing peptidoglycan chains has been performed for the first time and has allowed us to highlight the peculiarities of their binding at the formation of 3-3 cross-linkages, as well as to build a full-atom model of L,D-transpeptidase 2 for the screening and optimizing of inhibitors' structures...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461972/spheroids-of-her2-positive-breast-adenocarcinoma-for-studying-anticancer-immunotoxins-in-vitro
#10
I V Balalaeva, E A Sokolova, A D Puzhikhina, A A Brilkina, S M Deyev
Tumor response to therapeutic treatment is largely determined by its heterogeneity and the presence of intercellular junctions, hindering the penetration of large molecules deep into the three-dimensional structure of the tumor. In that context, 3D in vitro tumor models such as cancer cell spheroids are becoming increasingly popular. We obtained spheroids of human breast adenocarcinoma SKBR-3 overexpressing the HER2 cancer marker. The toxicity of HER2-targeted immunotoxin 4D5scFv-PE40 against spheroids was shown to be several orders of magnitude lower compared to a monolayer cell culture...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461971/cholesterol-in-the-pathogenesis-of-alzheimer-s-parkinson-s-diseases-and-autism-link-to-synaptic-dysfunction
#11
A M Petrov, M R Kasimov, A L Zefirov
In our previous review, we described brain cholesterol metabolism in control conditions and in the case of some rare neurological pathologies linked to defects in the genes which are directly involved in the synthesis and/or traffic of cholesterol. Here, we have analyzed disruptions in cholesterol homeostasis in widespread neurodegenerative diseases (Alzheimer's and Parkinson's diseases) and autism spectrum disorders. We particularly focused on the synaptic dysfunctions that could arise from changes in both membrane cholesterol availability and oxysterol production...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461970/proteomics-for-the-investigation-of-mycobacteria
#12
J A Bespyatykh, E A Shitikov, E N Ilina
The physiology of Mycobacterium tuberculosis, the causative agent of tuberculosis, is being studied with intensity. However, despite the genomic and transcriptomic data available today, the pathogenic potential of these bacteria remains poorly understood. Therefore, proteomic approaches seem relevant in studying mycobacteria. This review covers the main stages in the proteomic analysis methods used to study mycobacteria. The main achievements in the area of M. tuberculosis proteomics are described in general...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28461969/engineering-chimeric-antigen-receptors
#13
S V Kulemzin, V V Kuznetsova, M Mamonkin, A V Taranin, A A Gorchakov
Chimeric antigen receptors (CARs) are recombinant protein molecules that redirect cytotoxic lymphocytes toward malignant and other target cells. The high feasibility of manufacturing CAR-modified lymphocytes for the therapy of cancer has spurred the development and optimization of new CAR T cells directed against a broad range of target antigens. In this review, we describe the main structural and functional elements constituting a CAR, discuss the roles of these elements in modulating the anti-tumor activity of CAR T cells, and highlight alternative approaches to CAR engineering...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28050273/flavoprotein-minisog-cytotoxisity-can-be-induced-by-bioluminescence-resonance-energy-transfer
#14
E I Shramova, G M Proshkina, S P Chumakov, Yu M Khodarovich, S M Deyev
In this study, we investigated the possibility of phototoxic flavoprotein miniSOG (photosensitizer) excitation in cancer cells by bioluminescence occurring when luciferase NanoLuc oxidizes its substrate, furimazine. We have shown that the phototoxic flavoprotein miniSOG expressed in eukaryotic cells in fusion with NanoLuc luciferase is activated in the presence of its substrate, furimazine. Upon such condition, miniSOG possesses photoinduced cytotoxicity and causes a 48% cell death level in a stably transfected cell line...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28050272/adjuvant-induced-arthritis-in-guinea-pigs
#15
O S Taranov, S N Yakubitskiy, T S Nepomnyashchikh, A E Nesterov, S N Shchelkunov
We propose a model of rheumatoid arthritis (RA) induced in outbred guinea pigs using a single subcutaneous injection of complete Freund's adjuvant to the hind paw. Histological examination of this model shows fibrin deposition on the surface of the synovial membrane, leukocyte infiltration of the synovial membrane and adjacent tissues, proliferation of the granulation tissue, and emergence of angioid areas, characteristic of RA. The cell response appears as an increase in the plasma cell count and development of follicle-like lymphoid infiltrates; erosion of the articular surface of the cartilage, frequently with deep cartilage destruction over large areas; and epiphysiopathy...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28050271/evolution-of-tumor-clones-in-adult-acute-lymphoblastic-leukemia
#16
S Yu Smirnova, Yu V Sidorova, N V Ryzhikova, K A Sychevskaya, E N Parovichnikova, A B Sudarikov
Clonal instability of a tumor cell population in acute lymphoblastic leukemia (ALL) may complicate the monitoring of a minimal residual disease (MRD) by means of patient-specific targets identified at the disease onset. Most of the data concerning the possible instability of rearranged clonal TCR and IG genes during disease recurrence were obtained for ALL in children. The appropriate features of adult ALL, which are known to differ from those of childhood ALL in certain biological characteristics and prognosis, remain insufficiently studied...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28050270/downregulation-of-purkinje-cell-activity-by-modulators-of-small-conductance-calcium-activated-potassium-channels-in-rat-cerebellum
#17
T V Karelina, Yu D Stepanenko, P A Abushik, D A Sibarov, S M Antonov
Small-conductance calcium-activated potassium channels (SK channels) are widely expressed in CNS tissues. Their functions, however, have not been well studied. Participation of SK channels in Purkinje cell (PC) pacemaker activity has been studied predominantly in vitro. Here we studied for the first time the effects of SK channel activation by NS309 or CyPPA on the PC simple spike frequency in vivo in adult (3 - 6 months) and aged (22 - 28 months) rats using extracellular microelectrode recordings. Both pharmacological agents caused a statistically significant decrease in the PC simple spike frequency...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28050269/a-cascade-of-thermophilic-enzymes-as-an-approach-to-the-synthesis-of-modified-nucleotides
#18
R S Esipov, Yu A Abramchik, I V Fateev, I D Konstantinova, M A Kostromina, T I Muravyova, K G Artemova, A I Miroshnikov
We propose a new approach for the synthesis of biologically important nucleotides which includes a multi-enzymatic cascade conversion of D-pentoses into purine nucleotides. The approach exploits nucleic acid exchange enzymes from thermophilic microorganisms: ribokinase, phosphoribosylpyrophosphate synthetase, and adenine phosphoribosyltransferase. We cloned the ribokinase gene from Thermus sp. 2.9, as well as two different genes of phosphoribosylpyrophosphate synthetase (PRPP-synthetase) and the adenine phosphoribosyltransferase (APR-transferase) gene from Thermus thermophilus HB27 into the expression vectors, generated high-yield E...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28050268/design-of-stable-%C3%AE-helical-peptides-and-thermostable-proteins-in-biotechnology-and-biomedicine
#19
A P Yakimov, A S Afanaseva, M A Khodorkovskiy, M G Petukhov
α-Helices are the most frequently occurring elements of the secondary structure in water-soluble globular proteins. Their increased conformational stability is among the main reasons for the high thermal stability of proteins in thermophilic bacteria. In addition, α-helices are often involved in protein interactions with other proteins, nucleic acids, and the lipids of cell membranes. That is why the highly stable α-helical peptides used as highly active and specific inhibitors of protein-protein and other interactions have recently found more applications in medicine...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28050267/the-role-of-bar-domain-proteins-in-the-regulation-of-membrane-dynamics
#20
T B Stanishneva-Konovalova, N I Derkacheva, S V Polevova, O S Sokolova
Many cellular processes are associated with membrane remodeling. The BAR domain protein family plays a key role in the formation and detection of local membrane curvatures and in attracting other proteins, including the regulators of actin dynamics. Based on their structural and phylogenetic properties, BAR domains are divided into several groups which affect membrane in various ways and perform different functions in cells. However, recent studies have uncovered evidence of functional differences even within the same group...
October 2016: Acta Naturae
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