Genetic Causes of Rare Forms of Inherited Retinal Distrophy

Tatyana Vasilyeva1, Andrey Marakhonov2, Vitaly Kadyshev3, Rena Zinchenko41Research Center for Medical Genetics, valyeva_debrie@mail.ru2Research Centre for Medical Genetics, marakhonov@generesearch.ru3Research Centre for Medical Genetics, vvh.kad@gmail.com4Research Centre for Medical Genetics, renazinchenko@mail.ru Retinal dystrophy is highly heterogeneous,  this “frequent among rare” inherited eye pathologies which result in blindness due to photoreceptors death. Though some common forms of retinal dystrophy are associated with well-known and years ago established genes, hundreds of others are found and kept being revealed to be involved in its pathogenesis. We reported 6 solved using next generation sequencing technology (whole exom sequencing) cases of hereditary retinitis pigmentosa in an advanced stage of the disease progression which were found to be associated with pathogenic nucleotide sequence variants in known genes PRPF31, IFT140, RGS9, RPGR, RP1, and IMPG2. All 6 analyzed cases were characterized by a similar clinical picture of the deisease at its terminal stage. NGS analysis is the only method for DNA-diagnostics of genetically diverse and clinically homogeneous forms of inherited retinal dystrophy.   

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Mechanisms of ischemic kidney tolerance in young and senescence-accelerated rats exposured to ischemic preconditioning or calorie restriction

Egor Plotnikov1, Nadezda Andrianova2, Stanislovas Jankauskas3, Irina Pevzner4, Ljubava Zorova5, Vasily Popkov6, Denis Silachev7, Natalia Kolosova8, Dmitry Zorov91A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, plotnikov@belozersky.msu.ru2A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, andnadya12@gmail.com3A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, jankauskas.ss@gmail.com4A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, irinapevzner@mail.ru5A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, lju_2003@list.ru6A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, popkov.vas@gmail.com7A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, silachev_dn@belozersky.msu.ru8Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), kolosova@bionet.nsc.ru9A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, zorov@belozersky.msu.ru Dietary restriction and ischemic preconditioning are the most efficient approaches ameliorating the severity of different pathological conditions. We investigated the protective potential of long-term calorie restriction and short ischemic preconditioning protocol in the model of acute kidney injury (AKI) in young Wistar and OXYS rats. In young rats, ischemic preconditioning, which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However, 6-month-old OXYS rats having signs of premature aging lost their ability to protect the ischemic kidney by IPC. However, CR of OXYS rats led to a significant decrease in creatinine and BUN levels after kidney ischemia, indicating significant protection.

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  • June 29, 2020
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Influence of Immobilized Subtilisins on Perfomance Indicators of Rat Heart in Experiment

Pavel Madonov1, Roman Knyazev2, Konstantin Ershov31Department of experimental pharamacology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences Novosibirsk, Russian Federation Department of pharmacology, clinical pharmacology and evidence-based medicine Novosibirsk State Medical University Novosibirsk, Russian Federation, Pmadonov@yandex.ru2Research Institute of Biochemistry -Branch of the Federal Research Center of Fundamental and Translational Medicine Department of pharmacology, clinical pharmacology and evidence based medicine Novosibirsk State Medical University Novosibirsk, Russian Federation, Knjazev_roman@mail.ru3Department of pharmacology, clinical pharmacology and evidence-based medicine Novosibirsk State Medical University,Novosibirsk, Russian Federation, Ershov_k@bk.ru Immobilized subtilisins are bacterial proteinases with high thrombolytic activity that can improve peripheral circulation by dissolving a blood clot and reducing the manifestations of endothelial dysfunction. This article presents materials on the effect of immobilized subtilisins on heart performance in an experiment. The action of these proteinases was studied on a model of an isolated rat heart according to Langendorff. For registration, heart rate (HR) and pressure developed by the left ventricle (HDL) were selected. When immobilized subtilisins were added, an increase in left ventricular contraction force and a decrease in heart rate were shown. The results show that immobilized subtilisins have positive inotropic and negative chronotropic effects.

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Whole genome of novel Lactobacillus fermentum HFD1 strain producing various antimicrobial metabolites

    Poster (download)   Georgii Ozhegov1, Monyr Nait Yahia2, Alexey Vasilchenko3, Natalya Gogoleva4, Dina Yarullina5, Airat Kaumov6 1Kazan Federal University, Kazan, Russia; Perm State Pharmaceutical Academy, Perm, Russia, georgii_provisor@mail.ru 2Kazan Federal University, Kazan, Russia, monyrnait94@gmail.com 3University of Tyumen, Tyumen, Russia, avasilchenko@gmail.com 4Kazan Federal University, Kazan, Russia; Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia, NEGogoleva@kpfu.ru 5Kazan Federal University, Kazan, Russia, kasfes@gmail.com 6Kazan Federal University, Kazan, Russia, kairatr@yandex.ru Lactobacilli, generally recognized as safe for humans, are characterized with high antagonistic properties. Among 40 strains of Lactobacilli isolated from the faeces of healthy humans, Lactobacillus fermentum HFD1 exhibited significant antimicrobial activity against various nosocomial pathogens. The genome of L.fermentum HFD1 was sequenced on Illumina MiSeq and ONT MinION instruments. After reads assembly 2 circular contigs with respective sizes of 2101878 bp and 5386 bp have been obtained. The raw reads alignment with BWA and post-assembly assessment showed that 99.9% of Illumina reads and 99.2% of MinION reads were mapped to assembled genome. The genome was read with 575x coverage for Illumina data and 454x coverage for MinION data. Based on genome alignment L. fermentum FTDC8312 was found as closest related strain. The BLAST search identified the short contig as similar to bacterophage phiX174. In the genome 2120 coding sequences (CDS) were predicted. Among them 606 were annotated as hypothetical without known biological role. By using CAMPr3, ADAM and AMPA services 5 CDSs with highest summary prediction score were identified as coding for antimicrobial peptides. Further validation of their antimicrobial activity in vitro is required.

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Opisthorchis felineus extracellular vesicles increase cell proliferation and migration rates of human H69 cholangiocytes

Poster (download) D.V. Ponomarev1, O. Zaparina2, M.Y. Pakharukova3, V.A. Mordvinov41Laboratory of Molecular Mechanisms of Pathological Processes Institute of Cytology and Genetics SB RAS, p.dmitr@outlook.com2Laboratory of Molecular Mechanisms of Pathological Processes Institute of Cytology and Genetics SB RAS, zp.oksana.93@gmail.com3Laboratory of Molecular Mechanisms of Pathological Processes Institute of Cytology and Genetics SB RAS, pmaria@yandex.ru4Laboratory of Molecular Mechanisms of Pathological Processes Institute of Cytology and Genetics SB RAS, mordvin@bionet.nsc.ru Opisthorchis felineus, is a food-borne liver trematode and the main cause of opisthorchiasis in Russia and Europe. It affects hepatobiliary system of fish-eating mammals, including humans. Opisthorchiasis is associated with chronic inflammation, biliary epithelium proliferation, liver fibrosis, and even might cause cholangiocarcinoma among chronically infected individuals. Secreted proteins and extracellular vesicles of liver flukes might play an important role in the development of pathology. We investigated the response of human H69 cholangiocytes and human hepatoma HepG2 cells to adult liver flukes and to extracellular vesicles released from the flukes. We have demonstrated high mitogenic and cell migration stimulating activity of flukes and EVs vesicles. The activity was specific for cholangiocytes, but not for HepG2 cells. Specific mitogenic effect of liver fluke extracellular vesicles on proliferation and migration of human cholangiocytes in vitro may reflect the mechanisms of development of precancerous biliary intraepithelial neoplasia during opisthorchiasis in vivo.

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Placental transcriptome co-expression analysis reveals key biomarkers and pathways of preeclampsia

Poster (download) Trifonova E.1, Zarubin A.2, Babovskaya A.3, Markov A.4, Stepanov V.51TNRMC RAS, Tomsk, Russia; SibMed, Tomsk, Russia, ekaterina.trifonova@medgenetics.ru2TNRMC RAS, Tomsk, Russia, aleksei.zarubin@medgenetics.ru3TNRMC RAS, Tomsk, Russia, anastasia.babovskaya@medgenetics.ru4TNRMC RAS, Tomsk, Russia, anton.markov@medgenetics.ru5TNRMC RAS, Tomsk, Russia, vadim.stepanov@medgenetics.ru Preeclampsia is a complication of pregnancy characterized by new-onset hypertension and proteinuria of gestation, with serious consequences for mother and infant. Although a vast amount of research has been performed on the pathogenesis of preeclampsia, the underlying mechanisms of this multisystemic disease have remained to be fully elucidated. We identified the significant role of disturbance of intercellular interactions and regulation of proteins modification in placental tissue during the development of the PE. Among the genes involved in these key pathways, 9 hub genes and 3 master regulators were identified from the co-expression and upstream analysis networks. The present study may provide a basis for exploring potential novel genes and pathways as therapeutic targets for preeclampsia.

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Quantitative differences in the proteomic composition of the blood serum of patients with simple and paranoid schizophrenia

Poster (download) Video (download) Smirnova Liudmila, Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute of Tomsk National Research Medical Center, Tomsk, Russia, lpsmirnova@yandex.ru Semke Arkadiy, the Department of Endogenous Disorders Mental Health Research Institute of Tomsk National Research Medical Center. Tomsk, Russia, arkan1959@mail.ru Zgoda Victor, Laboratory of systems biology, Institute of Biomedical Chemistry, Moscow, Russia, vic@ibmh.msk.su Ivanova Svetlsna, Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute of Tomsk National Research Medical Center, Tomsk, Russia, ivanovaniipz@gmail.com Dmitrieva Elena, Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute of Tomsk National Research Medical Center, Tomsk, Russia, lena-312tom@yandex.ru The work analyzed the protein spectrum of blood serum of simple and paranoid schizophrenia. A set of proteins in schizophrenia was mainly associated with responsible for protein synthesis and the processes of transduction and translation; immune response, oxidative stress and apotosis, cell compataminization and cell contacts. In the blood serum of patients in the general group of schizophrenia, a significant increase in the number of RIPK1, mGluR6 receptors was revealed in comparison with healthy people. In addition, the amount of mGluR6 was significantly higher in patients with a simple form of schizophrenia than in patients with a paranoid form (p = 0.021). A quantitative assessment of the specific minor proteins that we studied using labeled standard peptides showed an increase in their number depending on the severity of the disease (a simple form of schizophrenia, leading negative symptoms)

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Whole-exome Sequencing Association Studies On Impaired Spermatogenesis In Different Ethnic Groups In Russia

Semyon K. Kolmykov1, Gennadiy V.Vasiliev2, Mikhail P. Ponomarenko3, Maxim A. Kleshev4, Aleksandr V. Osadchuk5, Ludmila V. Osadchuk6 1Institute of Cytology and Genetics SB RAS, kolmykovsk@gmail.com 2Institute of Cytology and Genetics SB RAS, genn@bionet.nsc.ru 3FRC Institute of Cytology and Genetics SB RAS, pon@bionet.nsc.ru 4Institute of Cytology and Genetics SB RAS, max82cll@bionet.nsc.ru 5Institute of Cytology and Genetics SB RAS, osadchuk@bionet.nsc.ru 6Institute of Cytology and Genetics SB RAS, losadch@bionet.nsc.ru In this study we identified single nucleotide polymorphisms in whole-exome sequencing data for different ethnic groups in Russia: Slavs, Yakuts and Buryats, and investigated its associations with impaired spermatogenesis.

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Metabolic response of the Siberian frog Rana amurensis to anoxia

Sergei V. Shekhovtsov1, Nina A. Bulakhova2, Yuri P. Tsentalovich3, Ekaterina A. Zelentsova4, Daniil I. Berman51ICG SB RAS, Novosibirsk, Russia, shekhovtsov@bionet.nsc.ru2IBPN FEB RAS, Magadan, Russia, sigma44@mail.ru3ITC SB RAS, Novosibirsk, Russia, yura.tsentalovich@tomo.nsc.ru4ITC SB RAS, Novosibirsk, Russia, zelentsova.ekaterina@gmail.com5IBPN FEB RAS, Magadan, Russia, dberman@mail.ru The Siberian frog Rana amurensis is the only amphibian capable of surviving several months at almost complete anoxia. We performed 1H NMR metabolomics analysis for the liver and heart of the Siberian frog during normoxia and anoxia. We found that anoxia causes significant energetic stress with much less energy molecules available in the studied organs. This is accompanied by the accumulation of several end products, most significantly lactate, alanine, and succinate, as well as most amino acids.

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Possible effect of SNP TATA-boxes of human erythropoiesis gene promoters on cognitive disorders

Poster (download) Ekaterina Sharypova1, Irina Drachkova2, Irina Chadaeva3, Mikhail Ponomarenko4, Ludmila Savinkova5 1Institute of Cytology and Genetics of SB RAS, sharypova@bionet.nsc.ru 2Institute of Cytology and Genetics of SB RAS, drachkova@bionet.nsc.ru 3Institute of Cytology and Genetics of SB RAS, ichadaeva@bionet.nsc.ru 4Institute of Cytology and Genetics of SB RAS, pon@bionen.nsc.ru 5Institute of Cytology and Genetics of SB RAS, lksav@bionet.nsc.ru In recent years, there is increasing evidence that various forms of anemia, changes in the quantity and quality of blood cells, may be involved in the pathogenesis of various cognitive disorders accompanying Alzheimer’s and Parkinson’s diseases, depression of various degrees, etc. In addition to erythroid cells, hemoglobin has been shown to be widely expressed in non-erythroid cells, including neurons of different parts of the brain.В  We analyzed in silico and in vitro unannotated SNPs in TATA boxes of human genes involved in erythropoiesis. Experimental verification in vitro using the method of electrophoretic mobility shift assay (EMSA) showed the correspondence of prognosis and experimental data. The obtained estimates of the effect of TATA box SNP markers on the formation of TBP/TATA complexes make it possible to consider some SNP markers of erythroid genes as markers of cognitive disorders.

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