AIMS Genetics最新文献

{"title":"Esophageal cancer research today and tomorrow: Lessons from algae and other perspectives.","authors":"Vladlena Tiasto,&nbsp;Valeriia Mikhailova,&nbsp;Valeriia Gulaia,&nbsp;Valeriia Vikhareva,&nbsp;Boris Zorin,&nbsp;Alexandra Kalitnik,&nbsp;Alexander Kagansky","doi":"10.3934/genet.2018.1.75","DOIUrl":"https://doi.org/10.3934/genet.2018.1.75","url":null,"abstract":"<p><p>Esophageal cancer is an increasing concern due to poor prognosis, aggressive disease modalities, and a lack of efficient therapeutics. The two types of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are responsible for an estimated 450,000 annual deaths, with over 457,000 new patients diagnosed in 2015, making it the eighth most prevalent and the 10th most fatal cancer worldwide. As esophageal cancer prevalence continues to increase, and so does the pressing need for the development of new and effective strategies for the early diagnostics, prevention, and treatment of this cancer, as well for building the innovative research tools to understand the affected molecular mechanisms. This short review summarizes the current statistics and recent research of the problems and solutions related to the esophageal cancer, and offer a brief overview of its epidemiology, molecular alterations, and existing biomedical tools. We will discuss currently available research tools and discuss selected approaches we deem relevant to find new model systems and therapies for the future with the special focus on novel opportunities presented by the unique molecules found in algae, namely carbohydrates and lipids. Their remarkable chemical variability is connected to their striking structural and functional properties, which combined with the relative novelty of these compounds to cancer biology, warrants interest of the wide biomedical community to these molecules, especially in the esophageal cancer theory and practice.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel functional miR-143-5p recognition element in the Cystic Fibrosis Transmembrane Conductance Regulator 3'UTR.","authors":"Chiara De Santi, Sucharitha Gadi, Agnieszka Swiatecka-Urban, Catherine M Greene","doi":"10.3934/genet.2018.1.53","DOIUrl":"10.3934/genet.2018.1.53","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are small non-coding RNAs involved in regulation of gene expression. They bind in a sequence-specific manner to miRNA recognition elements (MREs) located in the 3' untranslated region (UTR) of target mRNAs and prevent mRNA translation. MiRNA expression is dysregulated in cystic fibrosis (CF), affecting several biological processes including ion conductance in the epithelial cells of the lung. We previously reported that miR-143 is up-regulated in CF bronchial brushings compared to non-CF. Here we identified two predicted binding sites for miR-143-5p (starting at residues 558 and 644) on the <i>CFTR</i> mRNA, and aimed to assess whether <i>CFTR</i> is a true molecular target of miR-143-5p. Expression of miR-143-5p was found to be up-regulated in a panel of CF vs non-CF cell lines (1.7-fold, P = 0.0165), and its levels were increased <i>in vitro</i> after 20 hours treatment with bronchoalveolar lavage fluid from CF patients compared to vehicle-treated cells (3.3-fold, P = 0.0319). Luciferase assays were performed to elucidate direct miRNA::target interactions and showed that miR-143-5p significantly decreased the reporter activity when carrying the wild-type full length sequence of <i>CFTR</i> 3'UTR (minus 15%, P = 0.005). This repression was rescued by the disruption of the first, but not the second, predicted MRE, suggesting that the residue starting at 558 was the actual active binding site. In conclusion, we here showed that miR-143-5p modestly but significantly inhibits CFTR, improving the knowledge on functional MREs within the <i>CFTR</i> 3'UTR. This could lead to the development of novel therapeutic strategies where miRNA-mediated CFTR repression is blocked thereby possibly increasing the efficacy of the currently available CFTR modulators.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47530035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rpb5, a subunit shared by eukaryotic RNA polymerases, cooperates with prefoldin-like Bud27/URI","authors":"V. Martínez-Fernández, F. Navarro","doi":"10.3934/genet.2018.1.74","DOIUrl":"https://doi.org/10.3934/genet.2018.1.74","url":null,"abstract":"Abstract Rpb5 is one of the five common subunits to all eukaryotic RNA polymerases, which is conserved in archaea, but not in bacteria. Among these common subunits, it is the only one that is not interchangeable between yeasts and humans, and accounts for the functional incompatibility of yeast and human subunits. Rpb5 has been proposed to contribute to the gene-specific activation of RNA pol II, notably during the infectious cycle of the hepatitis B virus, and also to participate in general transcription mediated by all eukaryotic RNA pol. The structural analysis of Rpb5 and its interaction with different transcription factors, regulators and DNA, accounts for Rpb5 being necessary to maintain the correct conformation of the shelf module of RNA pol II, which favors the proper organization of the transcription bubble and the clamp closure of the enzyme. In this work we provide details about subunit Rpb5's structure, conservation and the role it plays in transcription regulation by analyzing the different interactions with several factors, as well as its participation in the assembly of the three RNA pols, in cooperation with prefoldin-like Bud27/URI.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41561740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells","authors":"A. Morshneva, O. Gnedina, S. Svetlikova, V. Pospelov, M. Igotti","doi":"10.3934/genet.2018.1.41","DOIUrl":"https://doi.org/10.3934/genet.2018.1.41","url":null,"abstract":"Abstract HDAC inhibitors (HDACIs) induce irreversible cell cycle arrest and senescence in mouse embryonic fibroblasts transformed with E1A and c-Ha-Ras oncogenes (E1A+Ras cell line). The aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. It's known that HDACs regulate the ROS-dependent FoxO factors, which are responsible for cell growth, proliferation, and longevity. The characteristic ROS increase during aging may be responsible for the decreased HDAC activity, which facilitates the senescent-like phenotype. The objective of this study was to investigate the impact of FoxO transcription factors on HDACIs-induced senescence of E1A+Ras oncogenes transformed cells. This study shows the specific time-dependent effect of HDACI sodium butyrate treatment on FoxO proteins in E1A+Ras cells. Indeed, short-term treatment with NaB results in FoxO activation, which takes place through nuclear translocation, and accompanied by accumulation of such ROS scavengers as MnSOD and SOD2. However, prolonged treatment leads to extensive FoxO degradation and increased intracellular levels of ROS. This degradation is connected with NaB-induced activation of Akt kinase. All of these findings establish that one of the possible mechanism involved in NaB-induced senescence of transformed cells is mediated through down-regulation of FoxO transcription factors and ROS accumulation.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42816735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Our love-hate relationship with DNA barcodes, the Y2K problem, and the search for next generation barcodes.","authors":"Jeffrey M Marcus","doi":"10.3934/genet.2018.1.1","DOIUrl":"https://doi.org/10.3934/genet.2018.1.1","url":null,"abstract":"<p><p>DNA barcodes are very useful for species identification especially when identification by traditional morphological characters is difficult. However, the short mitochondrial and chloroplast barcodes currently in use often fail to distinguish between closely related species, are prone to lateral transfer, and provide inadequate phylogenetic resolution, particularly at deeper nodes. The deficiencies of short barcode identifiers are similar to the deficiencies of the short year identifiers that caused the Y2K problem in computer science. The resolution of the Y2K problem was to increase the size of the year identifiers. The performance of conventional mitochondrial <i>COI</i> barcodes for phylogenetics was compared with the performance of complete mitochondrial genomes and nuclear ribosomal RNA repeats obtained by genome skimming for a set of caddisfly taxa (Insect Order Trichoptera). The analysis focused on Trichoptera Family Hydropsychidae, the net-spinning caddisflies, which demonstrates many of the frustrating limitations of current barcodes. To conduct phylogenetic comparisons, complete mitochondrial genomes (15 kb each) and nuclear ribosomal repeats (9 kb each) from six caddisfly species were sequenced, assembled, and are reported for the first time. These sequences were analyzed in comparison with eight previously published trichopteran mitochondrial genomes and two triochopteran <i>rRNA</i> repeats, plus outgroup sequences from sister clade Lepidoptera (butterflies and moths). <i>COI</i> trees were not well-resolved, had low bootstrap support, and differed in topology from prior phylogenetic analyses of the Trichoptera. Phylogenetic trees based on mitochondrial genomes or <i>rRNA</i> repeats were well-resolved with high bootstrap support and were largely congruent with each other. Because they are easily sequenced by genome skimming, provide robust phylogenetic resolution at various phylogenetic depths, can better distinguish between closely related species, and (in the case of mitochondrial genomes), are backwards compatible with existing mitochondrial barcodes, it is proposed that mitochondrial genomes and <i>rRNA</i> repeats be used as next generation DNA barcodes.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression characterization and functional implication of the collagen-modifying Leprecan proteins in mouse gonadal tissue and mature sperm.","authors":"Sarah M Zimmerman,&nbsp;Roberta Besio,&nbsp;Melissa E Heard-Lipsmeyer,&nbsp;Milena Dimori,&nbsp;Patrizio Castagnola,&nbsp;Frances L Swain,&nbsp;Dana Gaddy,&nbsp;Alan B Diekman,&nbsp;Roy Morello","doi":"10.3934/genet.2018.1.24","DOIUrl":"https://doi.org/10.3934/genet.2018.1.24","url":null,"abstract":"<p><p>The Leprecan protein family which includes the prolyl 3-hydroxylase enzymes (P3H1, P3H2, and P3H3), the closely related cartilage-associated protein (CRTAP), and SC65 (Synaptonemal complex 65, aka P3H4, LEPREL4), is involved in the post-translational modification of fibrillar collagens. Mutations in <i>CRTAP</i>, <i>P3H1</i> and <i>P3H2</i> cause human genetic diseases. We recently showed that SC65 forms a stable complex in the endoplasmic reticulum with P3H3 and lysyl hydroxylase 1 and that loss of this complex leads to defective collagen lysyl hydroxylation and causes low bone mass and skin fragility. Interestingly, SC65 was initially described as a synaptonemal complex-associated protein, suggesting a potential additional role in germline cells. In the present study, we describe the expression of SC65, CRTAP and other Leprecan proteins in postnatal mouse reproductive organs. We detect SC65 expression in peritubular cells of testis up to 4 weeks of age but not in cells within seminiferous tubules, while its expression is maintained in ovarian follicles until adulthood. Similar to bone and skin, SC65 and P3H3 are also tightly co-expressed in testis and ovary. Moreover, we show that CRTAP, a protein normally involved in collagen prolyl 3-hydroxylation, is highly expressed in follicles and stroma of the ovary and in testes interstitial cells at 4 weeks of age, germline cells and mature sperm. Importantly, <i>CrtapKO</i> mice have a mild but significant increase in morphologically abnormal mature sperm (17% increase compared to WT). These data suggest a role for the Leprecans in the post-translational modification of collagens expressed in the stroma of the reproductive organs. While we could not confirm that SC65 is part of the synaptonemal complex, the expression of CRTAP in the seminiferous tubules and in mature sperm suggest a role in the testis germ cell lineage and sperm morphogenesis.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36665647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients","authors":"Farideh Zonozi, H. Mozdarani, M. Salimi, S. Mozdarani, P. Fallahi, S. Mozdarani, Z. Heidari","doi":"10.3934/genet.2017.4.202","DOIUrl":"https://doi.org/10.3934/genet.2017.4.202","url":null,"abstract":"Abstract About 10–15% of non-obstructive azoospermia (NOA) patients show AZFc microdeletion in their blood leukocytes. However, if AZF genes were involved in impaired spermatogenesis, a higher frequency of chromosomal microdeletions was expected. In this study the frequency of AZFc microdeletion was compared with TTY2 gene family, i.e., TTY2A2A and TTY2A12A in blood leukocytes of NOA patients and normal fertile control. In the present study 30 normal fertile individuals with mean age of 35.0 ± 6.0 and 30 NOA patients with mean age of 34.0 ± 7.0 were screened for microdeletion of TTY2L2A and TTY2L12A at Yq11 and Yp11 respectively and sequence-tagged site (STS) markers for AZFc gene using multiplex PCR technique. At the first step karyotyping was done for all subjects using standard G-banding technique to identify patients with normal karyotype as well as non-affected normal controls for molecular analysis. Results showed no AZFc microdeletion in normal and NAO patients whereas one TTY2L2A microdeletion in normal control (3.3%) and 4 in NOA (13.3%) was observed (p < 0.05). However our data indicated that 6 of 30 NOA patients (20%) showed TTY2L12A microdeletion whereas there was no observed microdeletion in normal control (p < 0.01). Results indicate that the studied genes might be involved in impaired spermatogenesis more effective than the routinely screened AZF genes in infertile men. Therefore, screening these genes along with AZF genes might be valuable for infertile patients. The reason why these genes are deleted from Y chromosome is not known but might be associated with genomic instability induced by environmental physico-chemical genotoxic agents.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47505012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for two types of nrDNA existing in Chinese medicinal fungus Ophiocordyceps sinensis","authors":"Chih-Sheng Chen, Ching-Tsan Huang, R. Hseu","doi":"10.3934/genet.2017.3.192","DOIUrl":"https://doi.org/10.3934/genet.2017.3.192","url":null,"abstract":"Abstract Nuclear ribosomal DNA (nrDNA) sequences are widely used in the molecular classification of fungi. Previous phylogenetic studies of highly-valued traditional Chinese medicinal fungus Ophiocordyceps sinensis were mostly based on 18S and internal transcribed spacer (ITS) regions (ITS1, 5.8S and ITS2) of nrDNA. However, the disparity manifest in the low sequences identities between different O. sinensis isolates has led to argumentative hypotheses for this phenomenon, such as the “species complex” or “cryptic species” hypotheses. In the present study, four types of nrDNA (GC, AT-1, AT-2, and T) were identified using four primer pairs to amplify the nrDNA of six O. sinensis isolates. We demonstrate that each O. sinensis isolate contained two types of nrDNA, the omnipresent GC-type and a coexistent type alternating between the remaining three. This crucial discovery challenges the established notion of one type of nrDNA per species. We therefore propose that the composition of nrDNA types should be taken into consideration in studies of fungal genetics and classification.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41722561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies","authors":"C. Ladeira, Lenka Smajdova","doi":"10.3934/genet.2017.3.166","DOIUrl":"https://doi.org/10.3934/genet.2017.3.166","url":null,"abstract":"Abstract Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44314626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico based identification and functional analyses of miRNAs and their targets in Cowpea (Vigna unguiculata L.)","authors":"Zareen Gul, M. Y. Barozai, M. Din","doi":"10.3934/genet.2017.2.138","DOIUrl":"https://doi.org/10.3934/genet.2017.2.138","url":null,"abstract":"Abstract Cowpea (Vigna unguiculata L.) is an important leguminous plant and a good diet due to presence of carbohydrate and high protein contents. Currently, only few cowpea microRNAs (miRNAs) are reported. This study is intended to identify and functionally analyze new miRNAs and their targets in cowpea. An in-silico based homology search approach was applied and a total of 46 new miRNAs belonging to 45 families were identified and functionally annotated from the cowpea expressed sequence tags (ESTs). All these potential miRNAs are reported here for the first time in cowpea. The 46 new miRNAs were also observed with stable hairpin structures with minimum free energy, ranging from −10 to −132 kcal mol−1 with an average of −40 kcal mol−1. The length of new cowpea miRNAs are ranged from 18 to 26 nt with an average of 21 nt. The cowpea miRNA-vun-mir4414, is found as pre-miRNA cluster for the first time in cowpea. Furthermore, a set of 138 protein targets were also identified for these newly identified 46 cowpea miRNAs. These targets have significant role in various biological processes, like metabolism, transcription regulation as transcription factor, cell transport, signal transduction, growth & development and structural proteins. These findings are the significant basis to utilize and manage this important leguminous plant-cowpea for better nutritional properties and tolerance for biotic and abiotic stresses.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45723190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}