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Журнальные статьи

1. U12116
Blechingberg J., Holm I.E., Nielsen A.L. Characterization and expression analysis in the developing embryonic brain of the porcine FET family: FUS, EWS, and TAF15 // Gene. 2012. Vol. 493, № 1. P. 27–35.

The FET protein family consists of FUS (TLS), EWS (EWSIU), and TAF15. The FET proteins bind DNA and RNA and are involved in transcriptional regulation and RNA processing. Translocations involving the FET genes have been identified in human sarcomas, and mutations in the FUS and TAF15 genes are associated with Amyotrophic lateral Sclerosis. We here describe the characterization of the porcine FET proteins and an expression analysis during embryonic brain development. The FET proteins are well conserved between pig and human. FET protein mutations associated with Amyotrophic Lateral Sclerosis affect evolutionary conserved amino acids. In cultured cells the porcine FET proteins have a nuclear localization with some specific cytoplasmic aggregation of TAF15 in neuronal progenitor cells. Immunohistochemical analyses supported a predominant nuclear localization, but also faint cytoplasmic localization. The FET proteins have similar expression profiles throughout the development of the embryonic porcine brain and most cell types appeared positive for expression. Quantitative RT-PCR analyses showed that the FET mRNA expression decreased during embryonic development of hippocampus and for FUS and EWS during embryonic development of cortex. FET mRNA expression was relatively constant in brain stem, basal ganglia, and cerebellum. Overall the FET protein localization and mRNA and protein expression analyses were concordant with previous analysis from the human brain. The presented results indicate that the porcine brain could be an alternative model for the future examination of the normal functions as well as neurological disease associated functions of the FET proteins. (C) 2011 Elsevier B.V. All rights reserved.


2. 01433334
Feith D.J., Pegg A.E., Fong L.Y.Y. Targeted expression of ornithine decarboxylase antizyme prevents upper aerodigestive tract carcinogenesis in p53-deficient mice // Carcinogenesis. 2013. Vol. 34, № 3. P. 570–576.

Upper aerodigestive tract (UADT) cancers of the oral cavity and esophagus are a significant global health burden, and there is an urgent need to develop relevant animal models to identify chemopreventive and therapeutic strategies to combat these diseases. Antizyme (AZ) is a multifunctional negative regulator of cellular polyamine levels, and here, we evaluate the susceptibility of keratin 5 (K5)-AZ transgenic mice to tumor models that combine chemical carcinogenesis with dietary and genetic risk factors known to influence human susceptibility to UADT cancer and promote UADT carcinogenesis in mice. First, p53(/-) and K5-AZ/p53(/-) (AZ/p53(/-)) mice were placed on a zinc-deficient (ZD) or zinc-sufficient (ZS) diet and chronically exposed to 4-nitroquinoline 1-oxide. Tongue tumor incidence, multiplicity and size were substantially reduced in both ZD and ZS AZ/p53(/-) mice compared with p53(/-). AZ expression also reduced progression to carcinoma in situ or invasive carcinoma and decreased expression of the squamous cell carcinoma biomarkers K14, cyclooxygenase-2 and metallothionein. Next, AZ-expressing p53(/-) and p53 null mice were placed on the ZD diet and treated with a single dose of N-nitrosomethylbenzylamine. Regardless of p53 status, forestomach (FST) tumor incidence, multiplicity and size were greatly reduced with AZ expression, which was also associated with a significant decrease in FST epithelial thickness along with reduced proliferation marker K6 and increased differentiation marker loricrin. These studies demonstrate the powerful tumor suppressive effects of targeted AZ expression in two distinct and unique mouse models and validate the polyamine metabolic pathway as a target for chemoprevention of UADT cancers.


3. U12116
Galetto C.D. et al. Isolation and nucleotide sequence analysis of the of Rhinella arenarum beta-catenin: An mRNA and protein expression study during the larval stages of the digestive tract development // Gene. 2012. Vol. 511, № 2. P. 256–264.

beta-catenin interacts with several proteins mediating key biological processes, such as cadherin-mediated cell-cell adhesion as well as signal transduction. This work was done to establish the molecular basis and regulation of the formation pattern of cadherin/beta-catenin-mediated adherens junctions, using an animal model of unknown gene sequence, the toad Rhinella arenarum. A Rhinella arenarum beta-catenin homolog was isolated from larval tissue, their sequence compared and analyzed with those of eight other vertebrates using bioinformatics tools. The mRNA and protein expression levels of beta-catenin were determined during the development of Rhinella arenarum digestive tract both by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry-morphometry respectively. Using Xenopus laevis frog specific primers, a fragment 539 bp of Rhinella arenarum toad beta-catenin cDNA was obtained and sequenced. The resulting putative sequence of 177 amino acids showed high similarity at the amino acid level (97%) when compared to other six vertebrates (Xenopus laevis, Xenopus tropicalis, Mus musculus, Rattus norvegicus, Bos taurus and Homo sapiens), with sequences and structural domains characteristic of catenins. Subsequently, using primers specifically designed for Rhinella arenarum nucleotide sequence, beta-catenin-mRNA increasing levels were found during the Rhinella arenarum metamorphosis. Finally, increasing beta-catenin protein expression during development has confirmed the specificity the detection of Rhinella arenarum beta-catenin. Summarizing, we have isolated and sequenced a beta-catenin-homologue sequence from the Rhinella arenarum toad, which is highly conserved between species, and following we have detected beta-catenin mRNA and protein levels during their digestive tract development. (C) 2012 Elsevier B.V. All rights reserved.


4. U21083
Schoggins J.W. et al. A diverse range of gene products are effectors of the type I interferon antiviral response // Nature. 2011. Vol. 472, № 7344. P. 481-U545.

Nature | Letter Print Share/bookmark ????? A diverse range of gene products are effectors of the type I interferon antiviral response John W. Schoggins, Sam J. Wilson, Maryline Panis, Mary Y. Murphy, Christopher T. Jones, Paul Bieniasz & Charles M. Rice Affiliations Contributions Corresponding author Nature 472, 481–485 (28 April 2011) doi:10.1038/nature09907 Received 20 May 2010 Accepted 03 February 2011 Published online 10 April 2011 Corrigendum (July, 2015) Article tools PDF Citation Rights & permissions Article metrics The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago1, 2, 3, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1) and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1 and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system.


5. U12116
Tessier S.N., Storey K.B. Myocyte enhancer factor-2 and cardiac muscle gene expression during hibernation in thirteen-lined ground squirrels // Gene. 2012. Vol. 501, № 1. P. 8–16.

Many small mammals turn to hibernation to survive the winter, cycling through bouts of prolonged torpor where metabolic rate and body temperature fall to low levels. Remarkably, hypertrophy is promoted in cardiac muscle to support the stronger contractions needed in the cold. We proposed that altered expression of mRNA/protein levels of myocyte enhancer factor-2 (MEF2A, MEF2C) transcription factors and downstream targets (e.g., desmin, glucose transporter 4, and myomesin 1) would aid cardiac muscle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) in meeting challenges associated with hibernation. Gene and protein responses were compared over six conditions: control (euthermic animals in a 5 degrees C cold room), entrance into torpor, short and long torpors, arousal and interbout. Mef2a relative transcript levels were significantly elevated from controls contributing to increases in MEF2A protein levels throughout the torpor-arousal bout In addition, levels of phosphorylated, activated MEF2A (Thr312) correlated with increases in MEF2A-DNA binding. MEF2C transcript/protein levels were significantly elevated over controls at selected sampling points whereas phosphorylated/activated MEF2C (Ser387) levels rose during torpor and DNA binding was most prominent during entrance into torpor. Some gene targets of MEF2 action were also upregulated. Desmin transcript levels remained constant whereas enhanced protein expression occurred during entrance into torpor. Glut4 transcript levels were enhanced in arousal and protein expression was elevated over all five sampling points during torpor/arousal. Myomesin 1 transcript levels increased between early torpor and early arousal and protein levels increased during entrance and deep torpor. These data provide insights into the changes in gene/protein in expression that help to prepare cardiac muscle for hibernation. (C) 2012 Elsevier B.V. All rights reserved.


6. U07870
Watson E. et al. Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits // Cell. 2014. Vol. 156, № 4. P. 759–770.

Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology.


7. U12116
Xu R. et al. A genome-wide analysis of the RNA helicase gene family in Solanum lycopersicum // Gene. 2013. Vol. 513, № 1. P. 128–140.

Helicases belong to a class of molecular motor proteins that are found in yeast, animals, and plants. The helicase family is divided into three subfamilies, including the DEAD-box, DEAH-box and DExD/H-box helicases, which are classified based on variations within a common motif, known as motif II. The RNA helicases are involved in every step of RNA metabolism, including nuclear transcription, pre-mRNA splicing, ribosome biogenesis, nucleocytoplasmic transport, translation, RNA decay, and organellar gene expression. The RNA helicase protein family plays a crucial role in plant growth and development as well as in response to biotic and abiotic stresses. However, unlike Arabidopsis, no detailed information regarding the RNA helicase family is currently available for tomato (Solanum lycopersicum) due to a limited number of whole-genome sequences. In this study, we identified a total of 157 RNA helicase genes in the tomato genome. According to the structural features of the motif II region, we classified the tomato RNA helicase genes into DEAD-box, DEAH-box and DExD/H-box helicase genes. But there are 27 RNA helicases not belonging to this three subfamilies, we called that "other helicase". We mapped the 157 RNA helicase genes onto the tomato chromosomes, which range from chr01 to chr12. Microarray and expressed sequence tag data showed that many of these RNA helicase proteins may be involved in diverse biological processes and responses to various stresses. To our knowledge, this is the first report of a genome-wide analysis of the tomato RNA helicase gene family. This study provides valuable information for understanding the classification and putative functions of the RNA helicase gene family in Solanaceae. (c) 2012 Elsevier B.V. All rights reserved.


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