1,720,985 research outputs found
G-QUADRUPLEXES IN THE HIV-1 GENOME AS ANTIVIRAL TARGETS
Get PDFG-quadruplexes are non-canonical nucleic acid structures: their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they act as silencers in the promoter regions of human genes and putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Moreover, they have been proposed to be directly involved in gene regulation at the level of transcription. We investigated G-quadruplex formation in the HIV-1 proviral genome to assess the potential for viral inhibition through G-quadruplex stabilization. Here we show that the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional regulation with striking similarities to eukaryotic promoters and that treatment with a G-quadruplex ligand inhibits HIV-1 infectivity. In addition, we found three conserved putative G-quadruplex forming sequences uniquely clustered in the coding region for the accessory protein Nef that were efficiently stabilized or induced by G-quadruplex ligands. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. Finally, a comprehensive screening of G-quadruplex ligands against HIV-1 disclosed significant potential of some of them as HIV-1 inhibitors, likely with a G-quadruplex-mediated mechanism of action. These findings open up the possibility of inhibiting the HIV-1 by G-quadruplex-interacting small molecules, providing a new pathway to the development of anti-HIV-1 drugs with unprecedented mechanism of action
Supplementary_submission_PROGNOSTIC_ROLE_OF_PIK3CA_AND_TP53 – Supplemental material for Prognostic role of PIK3CA and TP53 in human papillomavirus–negative oropharyngeal cancers
No full textSupplemental material, Supplementary_submission_PROGNOSTIC_ROLE_OF_PIK3CA_AND_TP53 for Prognostic role of PIK3CA and TP53 in human papillomavirus–negative oropharyngeal cancers by Carlo Resteghini, Federica Perrone, Rosalba Miceli, Cristiana Bergamini, Salvatore Alfieri, Ester Orlandi, Marco Guzzo, Roberta Granata, Donata Galbiati, Stefano Cavalieri, Laura Locati, Lisa Licitra and Bossi Paolo in Tumori Journal</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses
Get PDFG-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NFκB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Visualization of DNA G-quadruplexes in herpes simplex virus 1-infected cells
Get PDFWe have previously shown that clusters of guanine quadruplex (G4) structures can form in the human herpes simplex-1 (HSV-1) genome. Here we used immunofluorescence and immune-electron microscopy with a G4-specific monoclonal antibody to visualize G4 structures in HSV-1 infected cells. We found that G4 formation and localization within the cells was virus cycle dependent: viral G4s peaked at the time of viral DNA replication in the cell nucleus, moved to the nuclear membrane at the time of virus nuclear egress and were later found in HSV-1 immature virions released from the cell nucleus. Colocalization of G4s with ICP8, a viral DNA processing protein, was observed in viral replication compartments. G4s were lost upon treatment with DNAse and inhibitors of HSV-1 DNA replication. The notable increase in G4s upon HSV-1 infection suggests a key role of these structures in the HSV-1 biology and indicates new targets to control both the lytic and latent infection
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