Репозиторий Университета

© 2019 by the authors. Cutaneous leishmaniasis (CL) is one of the most important infectious diseases in the world and is increasing day by day. No effective vaccine has been made against this disease, so far. An important issue with this disease is the development of drug resistance or no response to drug, which is going to spreading that its mechanism has not yet been completely identified. The main aim of this study was to assessment the expression of RNAPII gene in no response to drug and susceptible isolates of Leishmania major. The patients with CL from the central and North of Iran were considered for this study. The samples were transferred in RNAlater solution and stored in -20 °C. RNA extraction and cDNA synthesis were performed. The gene expression analysis was done with SYBR Green Real Time PCR Written informed consent was filled up by patients and then information forms were written based on Helsinki declaration. Statistical analysis was done with SPSS (16.0; SPSS Inc, Chicago) using independent t-test. P ≤ 0.05 was considered significant. It was observed that the gene expression of RNAPII in the no response to drug isolates was lower than that the one in drug sensitive isolates. A change in the expression of RNAP II in no response to drug isolates of L. major can indicate the potential role of this gene in the related mechanism.

© 2019, Pleiades Publishing, Inc. Abstract: Genetic engineering is considered as background for crop protection against pest damage by adding new genes inside the grains. Rice, like other cereals is included in gene engineering experiments. The questions about possible gene transfer related to food safety appear. It is important to find any additional genes or fragments in animal tissues after consumption of genetically modified (GM) food. Therefore, in this study, the remaining of CryIA(b) gene and P35 were assessed in the liver of rats fed with GM rice. This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. Overall, 20 male and 20 female SD rats were fed by pellets made by GM rice in 50% of needed carbohydrate for 90 days. Then, sampling was done from rats liver. DNA extraction was done based on the protocol. The quality and quantity of the extracted DNA was done by agarose gel electrophoresis and spectrophotometry, respectively. Detection of GM genes residues, including CryIA(b), P35, and T35 was done by Polymerase Chain Reaction using specific primer pairs. The results were analyzed by agarose gel electrophoresis alongside with 50 bp DNA ladder. The results were compared with the ones in control groups with feeding by standard pellet of non-modified rice. All amplification tests were done in triplicates. Analysis of the amplification of P35, CryIA(b) and T35 showed no residues inside the liver tissue. The results showed no significant difference in the presence of transgenic gene of cryIA(b), T35, and P35 in the liver tissue between the control and experiment groups. Therefore, this study rejects the possibility of gene settle of GM rice gene residues in liver tissue of the animal model studied.

© Ivyspring International Publisher. Stem cells (SCs) research is one of the most promising approaches to regenerative medicine. Our understanding of SCs biology and their potential role in tissue repairing has notably increased during the last few years. Mesenchymal stem cells (MSCs) are present in almost all human tissues, including oral and dental tissues (dental-derived stem cells or DDSCs). Despite many doubts and too many pitfalls still affect regenerative dentistry; however, it represents an exciting challenge for the next generations of young dentists. Educating and training in regenerative medicine the new generation of researchers is of utmost importance, albeit often underestimated: regenerative dentistry represents a big opportunity for the next generations of researchers and clinicians, and this review report underlines that dental schools should pay more attention to teachings of strategic subjects, such as cell biology, molecular biology and tissue engineering.

© 2018, Pleiades Publishing, Ltd. The gene for Kunitz peptidase inhibitor-like protein (KPILP) contains nested alternative open reading frame (aORF) that controls expression of the maternal mRNA. The content of NbKPILP mRNA in intact leaves of Nicotiana benthamiana plant is low but increases significantly upon extended dark exposure or when foreign nucleic acid is overexpressed in the cells. The NbKPILP gene promoter along with the expressed nested aORF are likely to play an important role in maintaining the levels of NbKPILP mRNA. To elucidate the role of NbKPILP promoter, we isolated a fragment of N. benthamiana chromosomal DNA upstream of the NbKPILP transcription start, sequenced it, and created constructs in which reporter E. coli uidA gene coding for β-D-glucuronidase (GUS) was placed under control of the NbKPILP promoter. By assessing the efficacy of uidA mRNA synthesis directed by the NbKPILP promoter and 35S promoter of the cauliflower mosaic virus in a transient expression system, we showed that the levels of GUS accumulation were comparable for both promoters. Prolonged incubation of the agroinjected plants in the darkness stimulated accumulation of the uidA mRNA directed by the NbKPILP promoter. Our experiments indicate that along with regulation at the transcriptional level, expression of NbKPILP mRNA can be affected by expression of the nested aORF controlled by the polypurine block (PPB) located upstream of its start codon, since introduction of mutations in the PPB resulted in significant accumulation of the NbKPILP mRNA. Nucleotide replacement in the aORF start codon led to the drastic increase in the amounts of NbKPILP mRNA and its protein product.

© 2018 Radboud University Medical Center Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most common neurodevelopmental disorder in childhood. In recent decades, it has been appreciated that in a substantial number of cases the disorder does not remit in puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is characterised by substantial comorbidity including substance use, depression, anxiety, and accidents. However, course and symptoms of the disorder and the comorbidities may fluctuate and change over time, and even age of onset in childhood has recently been questioned. Available evidence to date is poor and largely inconsistent with regard to the predictors of persistence versus remittance. Likewise, the development of comorbid disorders cannot be foreseen early on, hampering preventive measures. These facts call for a lifespan perspective on ADHD from childhood to old age. In this selective review, we summarise current knowledge of the long-term course of ADHD, with an emphasis on clinical symptom and cognitive trajectories, treatment effects over the lifespan, and the development of comorbidities. Also, we summarise current knowledge and important unresolved issues on biological factors underlying different ADHD trajectories. We conclude that a severe lack of knowledge on lifespan aspects in ADHD still exists for nearly every aspect reviewed. We encourage large-scale research efforts to overcome those knowledge gaps through appropriately granular longitudinal studies.

The atherosclerosis is considered among the most prevalent diseases. In Russia, N. N. Anitchkov and A. L. Miasnikov are founders of atherosclerosis studies. Valentina Iosifovna Miasnikova, doctor of medical sciences, professor of the Chair of Faculty Therapy #2 of the Sechenov University is one the numerous followers of A. L. Miasnikov. From the early 1960s, Valentina Iosifovna, proceeding with ideas of N. N. Anitchkov and A. L. Miasnikov, actively investigated pathogenesis of atherosclerosis. The professor V. I. Kalmykova, one of the first in Russia presented pathogenesis of atherosclerosis as a multi-factorial process and, combining theories existed at that moment, described effect of peroxidation of lipids on all stages of development of atherosclerotic plaque. She carried out a unique scientific investigation concerning studying intensity of peroxidation of lipids and antioxidant activity of lipids in patients with various degree of expression of ischemic heart disease. The gender characteristics of content of peroxides and antioxidant activity of lipids of blood serum were established. The research works of professor V. I. Kalmykova made an invaluable contribution into comprehension of pathogenesis of atherosclerosis and obtained an international approval. The scientific data obtained by V. I. Kalmykova were confirmed by studies of national and international researchers. Nowadays, the role of oxidation process in pathogenesis of atherosclerosis and ischemic heart disease is generally acknowledged.

© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston. The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19∗2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, p<0.038) and PI (30.6±20.0 vs. 18.1±16.3, p<0.013) were observed, and the rates of high platelet reactivity (HPR) were lower in CYP2C19∗1/∗1 than those in CYP2C19∗1/∗2+CYP2C19∗2/∗2 (16.2% vs. 53.8% p<0.0067). In comparison, no significant difference in PRU value and PI was observed at <5 days between the rest of polymorphisms (p>0.05). Based on the logistic regression analysis, CYP2C19∗2 (OR: 4.365, CI: 1.25-17.67, p=0.022) was an independent predictor of HPR at <5 days, as was the stent diameter (OR: 0.219, CI: 0.002-0.229, p=0.049). The remaining polymorphisms had no influence. The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.

© 2018 Elsevier Inc. Background: Corticotrophin-releasing hormone receptor-1 gene (CRHR1) variants have been implicated in mental health. However, little is known of the effects of CRHR1 on long-term mental health and behavior in presence of environmental stressors. We assess the effects of CRHR1 variant (rs17689918)-by-environment interactions on emotionality and behavioral traits, including anxiety, depression, aggression and antisocial behaviors. We also determine effects of rs17689918-by-environment-by-sex interactions on the above-mentioned outcomes. Methods: Genotypic assessments were carried out in 564 children (mean age 10 years, 52.5% females) from the ongoing longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS). Information on stressful life events and family relationships were available at baseline and information on behavioral and mental health outcomes (self- and parent-reports) were available at follow-up ages of 18 and 25 years. ANOVAs were used to determine associations of two-way CRHR1-by-environment and three-way CRHR1-by-sex-by-environment interactions on behavioral and mental health outcomes. Results: Two-way CRHR1 interaction effects showed associations between low familial warmth and hostility in individuals with the GG genotype. Associations of low familial warmth with aggression, of higher number of stressful life events with aggression, and of stressful live events with anxious-depressive symptoms were noted in male A-allele carriers and female GG homozygotes. Conclusion: CRHR1-by-familial environment interactions influence both outwardly-directed aggression as well as mood and anxiety disorder symptoms in a sex-specific manner. The type of environmental stressor can also influence effects of CRHR1 on behavioral and mental health outcomes.

© 2018 IEEE. This presentation will discusses recent studies on two photon polymerization process and examples of its application in TE.

© 2018 IEEE. This study aimed to develop the approach to the vasculature formation using LIFT-technology for tissue and organ engineering.

© 2018 IEEE. In this work, we present the first histological ex vivo (porcine gum) and in vivo (human) study of effects of fractional Er fiber laser (wavelength 1550 nm, peak power 25 W) on keratinized gum and alveolar mucosa in oral cavity.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Neonatal sepsis is one of the major causes of mortality and morbidity in newborns, greatly associated with severe acute kidney injury (AKI) and failure. Handling of newborns with kidney damage can be significantly different compared to adults, and it is necessary to consider the individuality of an organism’s response to systemic inflammation. In this study, we used lipopolysaccharide (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells damage in neonatal and adult rats. We found LPS-associated oxidative stress was more severe in adults compared to neonates, as judged by levels of carbonylated proteins and products of lipids peroxidation. In both models, LPS-mediated septic simulation caused apoptosis of kidney cells, albeit to a different degree. Elevated levels of proliferating cell nuclear antigen (PCNA) in the kidney dropped after LPS administration in neonates but increased in adults. Renal fibrosis, as estimated by smooth muscle actin levels, was significantly higher in adult kidneys, whereas these changes were less profound in LPS-treated neonatal kidneys. We concluded that in LPS-mediated AKI model, renal cells of neonatal rats were more tolerant to oxidative stress and suffered less from long-term pathological consequences, such as fibrosis. In addition, we assume that by some features LPS administration simulates the conditions of accelerated aging.

© 2018, Pleiades Publishing, Ltd. Fibroblast growth factor (FGF) plays an important role in human embryogenesis, angiogenesis, cell proliferation, and differentiation. Carcinogenesis is accompanied by aberrant constitutive activation of FGF receptors (FGFRs) resulting from missense mutation in the FGFR1-4 genes, generation of chimeric oncogenes, FGFR1-4 gene amplification, alternative splicing shift toward formation of mesenchymal FGFR isoforms, and FGFR overexpression. Altogether, these alterations contribute to auto-and paracrine stimulation of cancer cells and neoangiogenesis. Certain missense mutations are found at a high rate in urinary bladder cancer and can be used for non-invasive cancer recurrence diagnostics by analyzing urine cell pellet DNA. Chimeric FGFR1/3 and amplified FGFR1/2 genes can predict cell response to the targeted therapy in various oncological diseases. In recent years, high-throughput sequencing has been used to analyze exomes of virtually all human tumors, which allowed to construct phylogenetic trees of clonal cancer evolution with special emphasis on driver mutations in FGFR1-4 genes. At present, FGFR blockers, such as multi-kinase inhibitors, specific FGFR inhibitors, and FGF ligand traps are being tested in clinical trials. In this review, we discuss current data on the functioning of the FGFR family proteins in both normal and cancer cells, mutations in the FGFR1-4 genes, and mechanisms underlying their oncogenic potential, which might be interesting to a broad range of scientists searching for specific tumor markers and targeted anti-cancer drugs.

© Kolosova et al. P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1- encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an agerelated macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats, as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina, prohibiting their subretinal accumulation. Taken together, our results suggest that the p62DNA has a strong retinoprotective effect in AMD.

© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Experimental Biology. Potato is the most economically important non-cereal food crop. Tuber formation in potato is regulated by phytohormones, cytokinins (CKs) in particular. The present work studied CK signal perception in potato. The sequenced potato genome of doubled monoploid Phureja was used for bioinformatic analysis and as a tool for identification of putative CK receptors from autotetraploid potato cv. Désirée. All basic elements of multistep phosphorelay required for CK signal transduction were identified in the Phureja genome, including three genes orthologous to three CK receptor genes (AHK 2-4) of Arabidopsis. As distinct from Phureja, autotetraploid potato contains at least two allelic isoforms of each receptor type. Putative receptor genes from Désirée plants were cloned, sequenced and expressed, and the main characteristics of encoded proteins were determined, in particular their consensus motifs, modelled structure, ligand-binding properties, and ability to transmit CK signals. In all studied aspects the predicted sensor histidine kinases met the requirements for genuine CK receptors. Expression of potato CK receptors was found to be organ-specific and sensitive to growth conditions, particularly to sucrose content. Our results provide a solid basis for further in-depth study of CK signaling system and biotechnological improvement of potato.

© 2017 Informa UK Limited, trading as Taylor  &  Francis Group. Sub-constructs of morning–evening preference might be differentially related to polymorphisms in circadian clock genes. We previously reported significant association between a single nucleotide polymorphism in PER3 (rs2640909) and Morning but not Evening Lateness scale of the Sleep–Wake Pattern Assessment Questionnaire. To further explore such a scale-specific relationship, seven single nucleotide polymorphisms in five circadian clock genes were studied using exploratory and confirmatory samples (in total, n = 698). The association of rs2640909 with Morning Lateness scale was not replicated in the confirmatory sample but remained significant in the merged sample. Moreover, we found and confirmed an association of this scale with rs1159814 in RORα. The results provided further evidence for differential relationship of polymorphisms in circadian clock genes with morning and evening components of morning–evening preference. We also suggested possibility to take into account the pattern of geographic variation in allele frequency for prioritization of circadian clock polymorphisms in candidate gene studies.

© 2017 The mitochondrial membrane potential (ΔΨm) generated by proton pumps (Complexes I, III and IV) is an essential component in the process of energy storage during oxidative phosphorylation. Together with the proton gradient (ΔpH), ΔΨm forms the transmembrane potential of hydrogen ions which is harnessed to make ATP. The levels of ΔΨm and ATP in the cell are kept relatively stable although there are limited fluctuations of both these factors that can occur reflecting normal physiological activity. However, sustained changes in both factors may be deleterious. A long-lasting drop or rise of ΔΨm vs normal levels may induce unwanted loss of cell viability and be a cause of various pathologies. Among other factors, ΔΨm plays a key role in mitochondrial homeostasis through selective elimination of dysfunctional mitochondria. It is also a driving force for transport of ions (other than H+) and proteins which are necessary for healthy mitochondrial functioning. We propose additional potential mechanisms for which ΔΨm is essential for maintenance of cellular health and viability and provide recommendations how to accurately measure ΔΨm in a cell and discuss potential sources of artifacts.

© 2018 American Society for Microbiology.  The discovery of highly diverse nonprimate hepatoviruses illuminated the evolutionary origins of hepatitis A virus (HAV) ancestors in mammals other than primates. Marsupials are ancient mammals that diverged from other Eutheria during the Jurassic. Viruses from marsupials may thus provide important insight into virus evolution. To investigate Hepatovirus macroevolutionary patterns, we sampled 112 opossums in northeastern Brazil. A novel marsupial HAV (MHAV) in the Brazilian common opossum (Didelphis aurita) was detected by nested reverse transcription- PCR (RT-PCR). MHAV concentration in the liver was high, at 2.5 × 10 9 RNA copies/g, and at least 300-fold higher than those in other solid organs, suggesting hepatotropism. Hepatovirus seroprevalence in D. aurita was 26.6% as determined using an enzyme-linked immunosorbent assay (ELISA). Endpoint titers in confirmatory immunofluorescence assays were high, and marsupial antibodies colocalized with anti- HAV control sera, suggesting specificity of serological detection and considerable antigenic relatedness between HAV and MHAV. MHAV showed all genomic hallmarks defining hepatoviruses, including late-domain motifs likely involved in quasienvelope acquisition, a predicted C-terminal pX extension of VP1, strong avoidance of CpG dinucleotides, and a type 3 internal ribosomal entry site. Translated polyprotein gene sequence distances of at least 23.7% from other hepatoviruses suggested that MHAV represents a novel Hepatovirus species. Conserved predicted cleavage sites suggested similarities in polyprotein processing between HAV and MHAV. MHAV was nested within rodent hepatoviruses in phylogenetic reconstructions, suggesting an ancestral hepatovirus host switch from rodents into marsupials. Cophylogenetic reconciliations of host and hepatovirus phylogenies confirmed that hostindependent macroevolutionary patterns shaped the phylogenetic relationships of extant hepatoviruses. Although marsupials are synanthropic and consumed as wild game in Brazil, HAV community protective immunity may limit the zoonotic potential of MHAV.

© 2018 Walter de Gruyter GmbH, Berlin/Boston. The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts). Genotyping of 681G>A and 636G>A polymorphisms was performed by using polymerase real-time chain reaction. In both ethnic groups, Hardy-Weinberg equilibrium was followed in a distribution of alleles and genotypes in the population (p>0.05). The 681A allele frequency in the Yakut ethnic group was higher than in the Russian group: 17.53% vs. 8.39% (p=0.001). No statistically significant difference was found in the frequency of 636A in Yakuts and Russians with ACS: 3.92% vs. 3.50% (p=0.840). While comparing the frequency distribution of alleles 681A (13.49% vs. 14.54%, p=0.878) and 636A (7.94% vs. 7.80%, p=1) in patients with a gastric ulcer from Russian and Yakut ethnic groups, no significant difference was found in carrier frequency. The results of the present study may be helpful for developing guidelines for CYPC19 genotype-directed antiplatelet therapy for Yakut and Russian patients.