2,167 research outputs found
Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway
No full textBackground: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. Methods: MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. Results: A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3’UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3’UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Conclusions: Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis
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Ali Husain Mir Interview
No full textAli Husain Mir is a Bollywood lyricist and script writer and a professor of Management at William Paterson University. Mir visited the Hindi Urdu Flagship at the University of Texas at Austin to speak to Flagship students about his career in Urdu literature and Bollywood production. For this interview, Mir sat down with HUF directors, Syed Akbar Hyder and Herman van Olphen, to discuss his background in Urdu and the state of the language in modern India. Mir is the author of Anthems of Resistance, the definitive book on the All India Progressive Writers’ Movement; he is also an acclaimed lyricist and script-writer for Hindi and Urdu films (Iqbal, Dor). Mir’s oeuvre engages issues of religious minorities and secularism in South Asia.Asian Studie
A rare SNP in pre-miR-34a is associated with increased levels of miR-34a in pancreatic beta cells
No full textChanges in the levels of specific microRNAs (miRNAs) can reduce glucose-stimulated insulin secretion and increase beta-cell apoptosis, two causes of islet dysfunction and progression to type 2 diabetes. Studies have shown that single nucleotide polymorphisms (SNPs) within miRNA genes can affect their expression. We sought to determine whether miRNAs, with a known role in beta-cell function, possess SNPs within the pre-miRNA structure which can affect their expression. Using published literature and dbSNP, we aimed to identify miRNAs with a role in beta-cell function that also possess SNPs within the region encoding its pre-miRNA. Following transfection of plasmids, encoding the pre-miRNA and each allele of the SNP, miRNA expression was measured. Two rare SNPs located within the pre-miRNA structure of two miRNA genes important to beta-cell function (miR-34a and miR-96) were identified. Transfection of INS-1 and MIN6 cells with plasmids encoding pre-miR-34a and the minor allele of rs72631823 resulted in significantly (p < 0.05) higher miR-34a expression, compared to cells transfected with plasmids encoding the corresponding major allele. Similarly, higher levels were also observed upon transfection of HeLa cells. Transfection of MIN6 cells with plasmids encoding pre-miR-96 and each allele of rs41274239 resulted in no significant differences in miR-96 expression. A rare SNP in pre-miR-34a is associated with increased levels of mature miR-34a. Given that small changes in miR-34a levels have been shown to cause increased levels of beta-cell apoptosis this finding may be of interest to studies looking at determining the effect of rare variants on type 2 diabetes susceptibility. © 2013 The Author(s)
Maintaining Privacy During Psychosocial Research on the International Space Station
No full textConducting psychosocial research on the International Space Station (ISS) requires rigorous privacy precautions that exceed standard scientific human subject protocols. In our previous study involving crewmembers on Mir, and in our ongoing ISS work, special precautions were taken during each phase of the missions. Pre-flight, participants received detailed consent forms explaining that only group-level data would be presented, and they chose ID codes known only to them. In-flight, special procedures protected data during collection and transmission. Post-flight, our analytic strategy further masked participants’ identities, and participant representatives were invited to review manuscript drafts prior to publication. In this paper we describe lessons learned during our on-orbit studies and discuss their relation to maintaining privacy on studies of future long-duration space missions
MiR-124 overexpression time course analysis to identify predicted targets in total downregulated genes
No full text<p><b>Copyright information:</b></p><p>Taken from "Systematic identification of microRNA functions by combining target prediction and expression profiling"</p><p>Nucleic Acids Research 2006;34(5):1646-1652.</p><p>Published online 20 Mar 2006</p><p>PMCID:PMC1405822.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> () Counts of downregulated predicted targets at different time points after miR-124 transfections. () The percentages of predicted targets in total downregulated genes
p53 represses the oncogenic Sno-MiR-28 derived from a SnoRNA
No full text© 2015 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs) that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs) are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation
A review of Nearctic and some related Anthribidae (Coleoptera)
No full textTaxonomy, synonymy, distribution, and biologies of Nearctic (and a few Neotropical and Pale arctic) Anthribidae are reviewed, new keys are provided, and four new genera and eleven new species are described. Allandrus Leconte, 1876 (=Tropiderinus Reitter, 1916). Anthribus Geoffrey, 1762 (=Pseudobrachytarsus Pierce, 1930). Araecerus Schoenherr, 1823 (=Araeocorynus Jekel, 1855); Araecerus coffeae Fabricius, 1801 (=Tropideres (Rhaphitropis) mateui Cobos, 1954). Brachycorynus n. gen., type species Tropideres rectus Leconte, 1876; congeneric: Homocloeus distentus Frieser, 1983 from Cuba and Florida, and B. hirsutus n. sp. from Texas. Choragus major n. sp., Ohio, etc., striolatus n. sp., Ohio, and exophthalmus n. sp., Virginia. Corrhecerus Schoenherr, 1826 (=Paranthribus Jordan, 1904) resulting in Corrhecerus rufescens (Jordan, 1904), new combination. Eurymycter Leconte, 1876, and Gonotropis Leconte, 1876, are removed from synonymy with Tropideres Schoenherr, 1823, and returned to full generic rank. Eusphyrus Leconte, 1876 is removed from synonymy with Ormiscus Waterhouse, 1845, and returned to full generic rank; Tropideres (Opisthotropis) vasconicus Hoffmann and Tempere, 1954, from France is transferred to Eusphyrus, with Opisthotropis a generic synonym; Eusphyrus pulicarius Boheman, 1859, Brasil, is transferred from Brachytarsus, and the species eusphyroides Schaeffer and quercus Schaeffer are transferred from Ormiscus. Gymnognathus triangularis n. sp., Texas. Habroxenus n. gen., type species H. politus n. sp., Texas and Maryland, also H. fuscus n. sp., Guatemala, and H. sarmenticola n. sp., Haiti. Neoxenus n. gen., type species N. versicolor n. sp., Texas, etc.; congeneric: Notioxenus ater and polius Jordan, 1907, Central America, andpallipes Suffrian, 1870, Cuba. Phoenicobiella trituberculata (Suffrian, 1870, Cuba) transferred from Toxonotus Lacordaire, 1866. Piesocorynus lateralis Jordan, 1906 (=P. virginicus Leng, 1918). Sicanthus n. gen., type species S. rhizophorae n. sp., Florida. Toxonotus bipunctatus Schaeffer, 1904 (=Neanthribus obtusus Jordan, 1906); Toxonotus penicellatus Schaeffer, 1906 (=Neanthribus segregus Jordan, 1906); Toxonotus vagus Horn, 1894 (=Neanthribus hieronymus Jordan, 1906). Trigonorhinus lepidus n. sp., California; Trigonorhinus limbatus Say, 1827 (=Brachytarsus plumbeus and B. vestitus Leconte, 1876, and Brachytarsoides minor, quadratus, quadratus ssp. nigrinus and rufodorsalis Dethlefsen, 1954); Trigonorhinus grise us Leconte, 1876 (=Brachytarsus riddelliae Schaeffer, 1906, and Brachytarsoides cylindratus, elongatus, nevadensis, nevadensis ssp. tigrinus, and vulgaris Dethlefsen, 1954); Trigonorhinus tomentosus Say, 1827 (=Brachytarsus paululus Casey, 1884, B. beyeri Schaeffer, 1906, B. franseria Barrett, 1931, and B. irregularis Tanner, 1934); Trigonorhinus zeae Wolfrum, 1931 (=Opanthribus trimaculatus Senoh, 1986); Trigonorhinus areolatus Boheman, 1845 (=Tropideres (Tropideres), bagueni Cobos, 1954, Spain). Introgressive hybridization is invoked for the Trigonorhinus limbatus-griseus complex. New keys are provided for the species of Brachycorynus, Choragus, Habroxenus, Neoxenus, Phoenicobiella, Trigonorhinus, and Eusphyrus, plus a new key to Nearctic tribes and genera, and a new Nearctic checklist. New distribution and life-history data are given for many species
John Tenniel\u27s Alice in wonderland illustrations and the creation of a wordless picture book for adults
No full textMagistrska naloga z naslovom "Ilustracije Johna Tenniela Alica v čudežni deželi ter izdelava slikanice brez besedila za odrasle" je sestavljena iz dveh delov. V prvem, tj. teoretičnem delu bomo s pomočjo literature in internetnih virov predstavili značilnosti slikanice brez besedila, avtorja romana Alice v čudežni deželi Lewisa Carrolla in avtorja ilustracij Sir Johna Tenniela. Glede na to, da magistrska naloga temelji na analizah ilustracij Alice v čudežni deželi, bomo opisali idejo za njihov nastanek, tehniko risanja in tiska ter njihove pomene in simbole. V drugem delu, tj. praktičnem delu pa bomo izdelali slikanico brez besedila za odrasle.The Master\u27s thesis titled "John Tenniel\u27s Alice in Wonderland illustrations and the creation of a wordless picture book for adults" consists of two parts. In the first, i.e. theoretical part, we will, with the help of literature and internet sources, present the characteristics of wordless picture book, the author of the novel Alice in Wonderland Lewis Carroll and the author of illustrations Sir John Tenniel. Considering that the thesis is based on the analysis of illustrations of Alice in Wonderland, we will describe the idea behind their creation, the drawing and printing technique and their meanings and symbols. In the second, i.e. practical part, we will create a wordless picture book for adults
MiR-34a Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells via the RBP2/NOTCH1/CYCLIN D1 Coregulatory Network
No full textSummaryMiR-34a was demonstrated to be upregulated during the osteogenic differentiation of human adipose-derived stem cells (hASCs). Overexpression of miR-34a significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of osteogenesis-associated genes in hASCs in vitro. Enhanced heterotopic bone formation in vivo was also observed upon overexpression of miR-34a in hASCs. Mechanistic investigations revealed that miR-34a inhibited the expression of retinoblastoma binding protein 2 (RBP2) and reduced the luciferase activity of reporter gene construct comprising putative miR-34a binding sites in the 3′ UTR of RBP2. Moreover, miR-34a downregulated the expression of NOTCH1 and CYCLIN D1 and upregulated the expression of RUNX2 by targeting RBP2, NOTCH1, and CYCLIN D1. Taken together, our results suggested that miR-34a promotes the osteogenic differentiation of hASCs via the RBP2/NOTCH1/CYCLIN D1 coregulatory network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration
The drosophila miR-310 cluster negatively regulates synaptic strength at the neuromuscular junction
No full textEmerging data implicate microRNAs (miRNAs) in the regulation of synaptic structure and function, but we know little about their role in the regulation of neurotransmission in presynaptic neurons. Here, we demonstrate that the miR-310–313 cluster is required for normal synaptic transmission at the Drosophila larval neuromuscular junction. Loss of miR-310–313 cluster leads to a significant enhancement of neurotransmitter release, which can be rescued with temporally restricted expression of mir-310–313 in larval presynaptic neurons. Kinesin family member, Khc-73 is a functional target for miR-310–313 as its expression is increased in mir-310–313 mutants and reducing it restores normal synaptic function. Cluster mutants show an increase in the active zone protein Bruchpilot accompanied by an increase in electron dense T bars. Finally, we show that repression of Khc-73 by miR-310–313 cluster influences the establishment of normal synaptic homeostasis. Our findings establish a role for miRNAs in the regulation of neurotransmitter release
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