The role of CPEB family proteins in the nervous system function in the norm and pathology
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01.12.2021 |
Kozlov E.
Shidlovskii Y.V.
Gilmutdinov R.
Schedl P.
Zhukova M.
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Cell and Bioscience |
10.1186/s13578-021-00577-6 |
0 |
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Posttranscriptional gene regulation includes mRNA transport, localization, translation, and regulation of mRNA stability. CPEB (cytoplasmic polyadenylation element binding) family proteins bind to specific sites within the 3′-untranslated region and mediate poly- and deadenylation of transcripts, activating or repressing protein synthesis. As part of ribonucleoprotein complexes, the CPEB proteins participate in mRNA transport and localization to different sub-cellular compartments. The CPEB proteins are evolutionarily conserved and have similar functions in vertebrates and invertebrates. In the nervous system, the CPEB proteins are involved in cell division, neural development, learning, and memory. Here we consider the functional features of these proteins in the nervous system of phylogenetically distant organisms: Drosophila, a well-studied model, and mammals. Disruption of the CPEB proteins functioning is associated with various pathologies, such as autism spectrum disorder and brain cancer. At the same time, CPEB gene regulation can provide for a recovery of the brain function in patients with fragile X syndrome and Huntington's disease, making the CPEB genes promising targets for gene therapy.
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Rodent and fly models in behavioral neuroscience: An evaluation of methodological advances, comparative research, and future perspectives
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01.01.2021 |
Moulin T.C.
Covill L.E.
Itskov P.M.
Williams M.J.
Schiöth H.B.
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Neuroscience and Biobehavioral Reviews |
10.1016/j.neubiorev.2020.11.014 |
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© 2020 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.
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Rodent and fly models in behavioral neuroscience: An evaluation of methodological advances, comparative research, and future perspectives
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01.01.2021 |
Moulin T.C.
Covill L.E.
Itskov P.M.
Williams M.J.
Schiöth H.B.
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Neuroscience and Biobehavioral Reviews |
10.1016/j.neubiorev.2020.11.014 |
0 |
Ссылка
© 2020 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.
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Developing zebrafish experimental animal models relevant to schizophrenia
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01.10.2019 |
Demin K.
Meshalkina D.
Volgin A.
Yakovlev O.
de Abreu M.
Alekseeva P.
Friend A.
Lakstygal A.
Zabegalov K.
Amstislavskaya T.
Strekalova T.
Bao W.
Kalueff A.
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Neuroscience and Biobehavioral Reviews |
10.1016/j.neubiorev.2019.07.017 |
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© 2019 Elsevier Ltd Schizophrenia is a severely debilitating, lifelong psychiatric disorder affecting approximately 1% of global population. The pathobiology of schizophrenia remains poorly understood, necessitating further translational research in this field. Experimental (animal) models are becoming indispensable for studying schizophrenia-related phenotypes and pro/antipsychotic drugs. Mounting evidence suggests the zebrafish (Danio rerio) as a useful tool to model various phenotypes relevant to schizophrenia. In addition to their complex robust behaviors, zebrafish possess high genetic and physiological homology to humans, and are also sensitive to drugs known to reduce or promote schizophrenia clinically. Here, we summarize findings on zebrafish application to modeling schizophrenia, as well as discuss recent progress and remaining challenges in this field. We also emphasize the need in further development and wider use of zebrafish models for schizophrenia to better understand its pathogenesis and enhance the search for new effective antipsychotics.
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Lysine-specific post-translational modifications of proteins in the life cycle of viruses
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02.09.2019 |
Loboda A.
Soond S.
Piacentini M.
Barlev N.
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Cell Cycle |
10.1080/15384101.2019.1639305 |
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© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. The process of protein post-translational modifications (PTM) is one of the critical mechanisms of regulation of many cellular processes, which makes it an attractive target for various viruses. Since viruses cannot replicate on their own, they have developed unique abilities to alter metabolic and signaling cell pathways, including protein PTMs, to ensure faithful replication of their genomes. This review describes several ways of how lysine-specific PTMs are used by various viruses to ensure its successful invasion and replication. Covalent modifications like acetylation, ubiquitination, and methylation form a complex system of reversible and often competing modifications, which adds an additional level of complexity to the system of regulation of the activity of host proteins involved in viral replication and propagation. In furthering these, we also describe the manner in which PTM pathways can also be accosted by various types of viruses to neutralize the host’s cellular mechanisms for anti-viral protection and highlight key areas for future therapeutic targeting and design.
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The Expression of Matryoshka Gene Encoding a Homologue of Kunitz Peptidase Inhibitor Is Regulated Both at the Level of Transcription and Translation
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01.10.2018 |
Sheshukova E.
Komarova T.
Ershova N.
Bronstein A.
Dorokhov Y.
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Biochemistry (Moscow) |
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© 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.
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Translation-oriented reading of scientific-technical texts vs ordinary reading: Psychological and psycholinguistic aspects
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01.01.2018 |
Dolzhikova A.
Kurilenko V.
Biryukova Y.
Glazova O.
Arzumanova R.
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XLinguae |
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© 2018, Slovenska Vzdelavacia Obstaravacia. All rights reserved. Translation-oriented reading makes it possible to identify the differences and similarities of the professional reading and ordinary reading in psychological and psycholinguistic terms. The translator should comprehend both the meaning of the source text and its linguistic form of representation in order to produce an adequate translation. The analysis of translation-oriented reading based on the cognitive approach suggests that the translator arrives at a concept representing the content and meaning to be retrieved from the text. The obtained results may be used for the future research connected with the professional translator’s training.
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60S dynamic state of bacterial ribosome is fixed by Yeast mitochondrial initiation factor 3
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01.01.2018 |
Levitskii S.
Derbikova K.
Baleva M.
Kuzmenko A.
Golovin A.
Chicherin I.
Krasheninnikov I.
Kamenski P.
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PeerJ |
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2 |
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Copyright © 2018 Levitskii et al. The processes of association and dissociation of ribosomal subunits are of great importance for the protein biosynthesis. The mechanistic details of these processes, however, are not well known. In bacteria, upon translation termination, the ribosome dissociates into subunits which is necessary for its further involvement into new initiation step. The dissociated state of the ribosome is maintained by initiation factor 3 (IF3) which binds to free small subunits and prevents their premature association with large subunits. In this work, we have exchanged IF3 in Escherichia coli cells by its ortholog from Saccharomyces cerevisiae mitochondria (Aim23p) and showed that Yeast protein cannot functionally substitute the bacterial one and is even slightly toxic for bacterial cells. Our in vitro experiments have demonstrated that Aim23p does not split E. coli ribosomes into subunits. Instead, it fixes a state of ribosomes characterized by sedimentation coefficient about 60S which is not a stable structure but rather reflects a shift of dynamic equilibrium between associated and dissociated states of the ribosome. Mitochondria-specific terminal extensions of Aim23p are necessary for “60S state” formation, and molecular modeling results point out that these extensions might stabilize the position of the protein on the bacterial ribosome.
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