The high risk of ovarian cancer is primarily associated with mutations in BRCA1 and BRCA2 genes. However, mutations in these explain only a small proportion of cases. Mutations in other genes are also involved in the disease. As a result of previous exome sequencing of DNA samples from breast cancer Germany patients with clinical signs of a hereditary form of the disease without major mutations in the BRCA1, BRCA2, CHEK2 and NBN genes, potentially pathogenic genetic variants in new breast and ovarian cancer candidate genes were selected. Selected as a result of bioinformatics analysis genes are involved in vital cell signaling pathways such as repair, apoptosis, cell cycle regulation, cell proliferation, migration, differentiation, as well as immune response and inflammation. Recently, biological microarray technologies have been widely used to study the general genetic variability throughout the human genome in order to determine genetic associations with the disease and search for genes involved in the pathogenesis of multifactorial pathologies. The use of such approaches can be very useful for identifying risk markers for the development and severity of diseases. Our case-control study is aimed at researching potentially pathogenic variants selected as a result of exome sequencing of DNA samples from Caucasian patients using microarray technology Fluidigm to assess their contribution to ovarian cancer pathogenesis in Bashkortostan. Most of the researched alleles were found with different frequencies among cases and controls; however, our data indicate that the researched potentially pathogenic variants do not contribute to ovarian cancer pathogenesis in Bashkortostan populations.
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8 ASSOCIATION OF 22 POTENTIAL PATHOGENIC VARIANTS.pdf | 688.03 KB |
Integration of Immature Neurons Maintain Unidirectional Connectivity of Pre-Existed Network In Vitro
Recovery of the neural networks after brain injury can be studied in vitro using cell patterning technologies such as microfluidics. In this study, neural tissue recovery of cortical networks was modeled in a three-chamber microfluidic chip by growing two weakly coupled neuronal networks and by plating new immature cells between it. The direction of synaptic connections was formed by the asymmetric design of the microchannels in the chip. We investigated dynamics of morphological characteristics of neurites growth through the microchannels and spiking activity propagation between the networks after integration of new cortical cells. The results can be used for the development of new approaches for brain functional recovery after injury.
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7 INTEGRATION OF IMMATURE NEURONS MAINTAIN.pdf | 848.87 KB |
The article considers the development of biocomposite materials as bacterial cellulose-based hydrogel, chitosan and alginate, plus physiologically active compounds – fusidic acid, resveratrol and dihydroquercetin. It has been found that the use of hydrogel systems derived from microbial polysaccharides and containing bacterial cellulose (BC) / sodium alginate with CaCl2 /sodium fusidate (SF) and BC/chitosan /sodium fusidate helps to reduce the intensity of lipid peroxidation processes and stabilize phospholipid and fatty acid composition of the skin. It is consistent with the findings of the authors on longer release of sodium fusidate from biocomposite materials of this composition. Therefore, the use of BC and chitosan in combination with sodium fusidate, which exhibits antibacterial properties, and the crosslinking of sodium alginate with calcium chloride solution proves to be the most effective for restoring the skin’s lipid composition and shortening the course of treatment. Most likely, this effect must be explained by the constant release of physiologically active compounds from hydrogel composites and its impact on damaged skin areas.
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6 EFFECT OF BIOCOMPOSITES ON BACTERIAL CELLULOSE-BASED HYDROGEL.pdf | 1.69 MB |
In the last decade, glial cells, primarily astrocytes, have received increasing attention in studying various aspects of brain functioning. Although astrocytes are not electrically excitable cells, they are able to generate and transmit Ca2+ signals, which can propagate from cell to cell, forming «calcium waves». Calcium signaling allows astrocytes to interact with each other, as well as regulate neuronal function. Despite numerous studies on calcium events in astrocytes under various pathological conditions, the features of astrocytic calcium dynamics in aging are currently understudied. Our work aimed to analyze the features of calcium activity in primary astrocyte cultures during physiological and accelerated aging, as well as to assess the effect of hypoxic damage on calcium activity. For this purpose, we developed an algorithm for the accurate detection of calcium events and the calculation of indicators describing the main parameters of calcium events in a cell. It was shown that the frequency of calcium event generation in astrocytes decreases during aging while their duration and amplitude increase. Hypoxia aggravates the changes caused by cell aging.
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5 FEATURES OF CALCIUM ACTIVITY OF ASTROCYTES.pdf | 740.15 KB |
The visceral system can influence consciousness and emotions. In this paper, we investigated whether the processing of short-term emotional stimuli along different phases of the cardiac cycle is selectively regulated. Emotional and neutral faces were presented to the volunteers during cardiac systole, when the release of blood from the heart causes arterial baroreceptors to centrally signal the strength and time of the heartbeat, and in diastole, the period between heartbeats when the baroreceptors are at rest. Participants passively observed the faces appearing in the oddball paradigm in immersive virtual reality (VR). Combining electroencephalography and electrocardiography, cardio synchronous ERP was recorded. The ERP data at the occipital Oz electrode demonstrate the dependence of emotional stimuli in respect to the cardiac cycle. ERP in VR were higher during diastole than systole. More specifically, the cardiac phase influenced late component P300 of the ERP, did not influence early P100 and affected P200 only to angry face. This new evidence that events related to cardiac function can modulate emotional perception in virtual reality might be one more prime example of how body feedback shapes emotions.
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4 FACE-RELATED ERP.pdf | 530 KB |
Erythrocytes, performing their basic oxygen transport function, simultaneously affect blood viscosity by changing the deformability of their structure, and also have a vasodilating effect on the walls of blood vessels using NO. An important role in this regulation is played by the purinergic signaling system, which was confirmed by this study of the morphofunctional parameters of red blood cells in the presence of ATP and sodium nitroprusside (SNP). We found that under the action of 0.5 mM ATP on red blood cells, the ability of hemoglobin (Hb) to bind oxygen decreases against the background of a slight increase in complexes with oxygen, while the total number of membrane-cytoskeletal proteins also decreases. This, in turn, is accompanied by a redistribution of Hb molecules and an increase in the area of red blood cells. In the presence of 5.0 mM ATP, the oxygen transport function of erythrocytes and the quantitative composition of membrane proteins change similarly, while the geometric height and volume of the cells are significantly reduced. The combined effect of 100 μM SNP and 0.5 mm ATP has the greatest effect on the conformation of hemoporphyrin molecules, which leads to a sharp increase in hemoglobin complexes with oxygen, while the affinity of hemoglobin for oxygen decreases. The membrane-cytoplasmic component of the cell also undergoes changes. Thus, ATP, both separately and in combination with SNP, affects the oxygen transport and regulatory function of red blood cells, activating the purinergic signaling pathway and triggering a cascade of adaptation reactions in the cell.
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3 STUDY OF THE RELATIONSHIP BETWEEN THE FUNCTIONING.pdf | 2.14 MB |
The paper focuses on studying the rheological properties of erythrocytes in patients with a new coronavirus infection in the acute period and during early convalescence. A significant decrease in erythrocyte membrane plasticity was found in all patients in the acute period of the disease and every second recovering patients in the early post-COVID period. An increase in the degree and rate of erythrocyte aggregation in a quarter of cases, regardless of the observation period, was accompanied by inhibition of erythrocyte disaggregation mechanisms, which can serve as a pathophysiological basis for the formation of hemorheological disorders both in the micro- and macrovasculature in the first 3 months after recovery.
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2 RHEOLOGICAL PROPERTIES OF ERYTHROCYTES.pdf | 604.31 KB |
This year Nobel Prize in Physiology or Medicine awarded to Swedish paleogeneticist Svante Pääbo demonstrated the significance of ancient genomes investigation, shedding bright light to the aDNA science. As an ancient DNA study has evolved from the 1980s to the present days it has experienced peak of inflated expectations, dramatic fall to trough of disillusionment and slope of enlightenment with exponential data accumulation after the successful introduction of NGS approach. Today ancient DNA study is a rapidly developing and facilitated by advanced technologies science that challenges our assumptions about the past by analyzing over a million-year-old ancient specimens. Here we provide an overview of peculiar properties of ancient DNA analysis of human and microbes genomes.
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1 PECULIARITIES OF WORKING WITH ANCIENT DNA.pdf | 432.64 KB |
B. pumilus metalloproteinase was firstly isolated and characterized by Kazan Federal University scientists. Primary structure analysis showed that the novel enzyme has no analogs among prokaryotic enzymes and occupies an intermediate position between two large families of the metzinkin clan metalloproteinases – adamalysins and astacins. These families are mainly represented by eukaryotic enzymes, which play an important role in human life and health. A more detailed study of the structure and functions of novel metalloproteinase requires an efficient expression system. B. pumilus metalloproteinase gene (mprBp) was cloned into the pGP382 expression vector under a strong constitutive promoter of the degQ36 gene (PdegQ36). The resulting construct was used to transform B. subtilis Δ6 strain. This strain was constructed by CRISPR/Cas9 genome editing technology with deletion of some prophage genes of B. subtilis 168. The functional role of prophage genes is poorly understood. It is possible that prophage deletion will increase the expression of secreted enzymes. For the transformed strain we determined the dynamics of growth and accumulation of proteolytic activity by hydrolysis of azocasein. The dynamics of proteolytic activity accumulation by this strain has a different character in contrast to the protease-deficient strains carrying the gene of the investigated enzyme. The result of this work was to obtain an effective producer strain of adamalizin-like metalloproteinase of B. pumilus, which can be used in the production of the enzyme for subsequent studies.
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12 CRISPR:Cas9-REDACTED BACILLUS SUBTILIS STRAIN.pdf | 636.91 KB |
Along with the wide spread of bacterial antibiotic resistance over the world, the treatment efficiency of infectious disease is greatly affected by the mixed biofilm formation by pathogenic bacteria. Staphylococcus aureus and Pseudomonas aeruginosa, a frequent cause of nosocomial infections, exhibit both synergistic and antagonistic interactions in co-culture, leading to various changes in the metabolic profile of bacteria, which in turn affect their sensitivity to antimicrobials. Here we show that S. aureus cell-free culture liquid exhibits bacteriostatic properties and increases the efficacy of antimicrobials against P. aeruginosa. Thus, the MICs of amikacin, gentamicin, and ciprofloxacin decreased 2-4 fold in the presence of cell-free supernatant of S. aureus 24 h culture. Furthermore, the combination of the latter with antimicrobials increased the efficacy of amikacin up to 64-fold. Thus, the combined use of cell-free culture liquid of S. aureus with broad-spectrum antibiotics can be used to increase the effectiveness of antimicrobial therapy of P. aeruginosa.
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11 CELL-FREE SUPERNATANT OF STAPHYLOCOCCUS AUREUS CULTURE.pdf | 911.25 KB |