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Takuya Furuta, Hiroaki Miyoshi, Satoru Komaki, Fumiko Arakawa, Motohiro Morioka, Koichi Ohshima, Mitsutoshi Nakada, Yasuo Sugita
Epithelioid glioblastoma (eGBM) is a rare variant of GBM which was adopted in the 2016 WHO classification. eGBM and pleomorphic xanthoastrocytoma (PXA) sometimes show overlapping features histologically and genetically, such as epithelioid pattern and a highly frequent V600E mutation in the gene for vRAF murine sarcoma viral oncogene homolog B1 (BRAF), respectively. Accurate diagnosis of these rare tumors is challenging according to the new criteria in the revised 2016 WHO classification. It is an urgent task to elucidate the biological properties of the tumors and to select appropriate treatment...
March 13, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Rosario Palacios, M Mayorga, C M González-Domenech, C Hidalgo-Tenorio, C Gálvez, L Muñoz-Medina, J de la Torre, A Lozano, M Castaño, M Omar, Jesús Santos
OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42...
January 2018: Journal of the International Association of Providers of AIDS Care
Anvita Bhargava, Xavier Lahaye, Nicolas Manel
The nuclear envelope is a physical barrier that isolates the cellular DNA from the rest of the cell, thereby limiting pathogen invasion. The Human Immunodeficiency Virus (HIV) has a remarkable ability to enter the nucleus of non-dividing target cells such as lymphocytes, macrophages and dendritic cells. While this step is critical for replication of the virus, it remains one of the less understood aspects of HIV infection. Here, we review the viral and host factors that favor or inhibit HIV entry into the nucleus, including the viral capsid, integrase, the central viral DNA flap, and the host proteins CPSF6, TNPO3, Nucleoporins, SUN1, SUN2, Cyclophilin A and MX2...
February 27, 2018: Cytokine & Growth Factor Reviews
Abid Qureshi, Akanksha Rajput, Gazaldeep Kaur, Manoj Kumar
A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository...
March 9, 2018: Journal of Cheminformatics
Roumen Voutev, Richard S Mann
Effective genome engineering should lead to a desired locus change with minimal adverse impact to the genome itself. However, flanking loci with site-directed recombinase recognition sites, such as those of the phage FC31 integrase, allows for creation of platforms for cassette exchange and manipulation of genomic regions in an iterative manner, once specific loci have been targeted. Here we show that a genomic locus engineered with inverted minimal phage FC31 attP/attB sites can undergo efficient recombinase-mediated cassette exchange (RMCE) in the fruit fly Drosophila melanogaster ...
March 9, 2018: G3: Genes—Genomes—Genetics
Savrina Manhas, Lina Ma, Vivien Measday
Nuclear pore complexes (NPCs) orchestrate cargo between the cytoplasm and nucleus and regulate chromatin organization. NPC proteins, or nucleoporins (Nups), are required for human immunodeficiency virus type 1 (HIV-1) gene expression and genomic integration of viral DNA. We utilize the Ty1 retrotransposon of Saccharomyces cerevisiae (S. cerevisiae) to study retroviral integration because retrotransposons are the progenitors of retroviruses and have conserved integrase (IN) enzymes. Ty1-IN targets Ty1 elements into the genome upstream of RNA polymerase (Pol) III transcribed genes such as transfer RNA (tRNA) genes...
March 5, 2018: Nucleic Acids Research
Li-Oon Chuah, Ahamed-Kamal Shamila Syuhada, Ismail Mohamad Suhaimi, Tajudin Farah Hanim, Gulam Rusul
This article describes the Pulsed-field gel electrophoresis clustering of the predominant Salmonella strains ( Salmonella ser. Albany, Salmonella ser. Brancaster, and Salmonella ser. Corvallis) isolated from poultry and processing environment in wet market and small-scale processing plant in Penang and Perlis, the northern states of Malaysia. Agar disk diffusion assay was performed to determine the phenotypic antibiotic resistance of these Salmonella strains. The most common antibiograms among the three predominant Salmonella serovars were reported...
April 2018: Data in Brief
Damien Bonnard, Erwann Le Rouzic, Sylvia Eiler, Céline Amadori, Igor Orlov, Jean-Michel Bruneau, Julie Brias, Julien Barbion, Francis Chevreuil, Danièle Spehner, Sophie Chasset, Benoit Ledoussal, François Moreau, Ali Saïb, Bruno P Klaholz, Stéphane Emiliani, Marc Ruff, Alessia Zamborlini, Richard Benarous
Recently, a new class of HIV-1 integrase (IN) inhibitors with a dual mode of action, called IN-LEDGF/p75 allosteric inhibitors (INLAIs), was described. Designed to interfere with the INLEDGF/p75 interaction during viral integration, unexpectedly, their major impact was on virus maturation. This activity has been linked to induction of aberrant IN multimerization, while inhibition of the IN-LEDGF/p75 interaction accounts for weaker antiretroviral effect at integration. Since these dual activities result from INLAI binding to IN at a single binding site, we expected that these activities co-evolved together, driven by the affinity for IN...
March 5, 2018: Journal of Biological Chemistry
Kazuhisa Honma, Satoshi Abe, Takeshi Endo, Narumi Uno, Mitsuo Oshimura, Tetsuya Ohbayashi, Yasuhiro Kazuki
Mouse artificial chromosome (MAC) vectors have several advantages as gene delivery vectors, such as stable and independent maintenance in host cells without integration, transferability from donor cells to recipient cells via microcell-mediated chromosome transfer (MMCT), and the potential for loading a megabase-sized DNA fragment. Previously, a MAC containing a multi-integrase platform (MI-MAC) was developed to facilitate the transfer of multiple genes into desired cells. Although the MI system can theoretically hold five gene-loading vectors (GLVs), there are a limited number of drugs available for the selection of multiple-GLV integration...
2018: PloS One
Clare Hannon, Abimael Cruz-Migoni, Olga Platonova, Robin L Owen, Joanne E Nettleship, Ami Miller, Stephen B Carr, Gemma Harris, Terence H Rabbitts, Simon E V Phillips
Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase in human cells. The crystal structure of the HIV integrase-binding domain (IBD) of LEDGF has been determined in the absence of ligand. IBD was overexpressed in Escherichia coli, purified and crystallized by sitting-drop vapour diffusion. X-ray diffraction data were collected at Diamond Light Source to a resolution of 2.05 Å. The crystals belonged to space group P21 , with eight polypeptide chains in the asymmetric unit arranged as an unusual octamer composed of four domain-swapped IBD dimers...
March 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
Nina S Atanasova, Camilla H Heiniö, Tatiana A Demina, Dennis H Bamford, Hanna M Oksanen
Extremely halophilic Archaea are the only known hosts for pleolipoviruses which are pleomorphic non-lytic viruses resembling cellular membrane vesicles. Recently, pleolipoviruses have been acknowledged by the International Committee on Taxonomy of Viruses (ICTV) as the first virus family that contains related viruses with different DNA genomes. Genomic diversity of pleolipoviruses includes single-stranded and double-stranded DNA molecules and their combinations as linear or circular molecules. To date, only eight viruses belong to the family Pleolipoviridae ...
February 28, 2018: Genes
Lucy Cheng, Laura J Marinelli, Noël Grosset, Sorel T Fitz-Gibbon, Charles A Bowman, Brian Q Dang, Daniel A Russell, Deborah Jacobs-Sera, Baochen Shi, Matteo Pellegrini, Jeff F Miller, Michel Gautier, Graham F Hatfull, Robert L Modlin
BACKGROUND: A remarkable exception to the large genetic diversity often observed for bacteriophages infecting a specific bacterial host was found for the Cutibacterium acnes (formerly Propionibacterium acnes) phages, which are highly homogeneous. Phages infecting the related species, which is also a member of the Propionibacteriaceae family, Propionibacterium freudenreichii, a bacterium used in production of Swiss-type cheeses, have also been described and are common contaminants of the cheese manufacturing process...
March 1, 2018: BMC Microbiology
Nacim Bouheraoua, Laurent Poirel, Baptiste Bourreau, Rémy Bonnin, Laurent Laroche, Thierry Naas, Patrice Nordmann
Integrons are genetic elements that can acquire and rearrange gene cassettes. The bla BEL-1 gene encodes an extended-spectrum β-lactamase, BEL-1, that is present at second position of the variable region of class 1 integrons identified in Pseudomonas aeruginosa The mobility of the bel-1 gene cassette was analyzed in physiological conditions and with the integrase gene being overexpressed. Cassette mobility in Escherichia coli was detected by excision/integration into the recipient integron In 3 on the conjugative plasmid R388, with the over-produced integrase...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Faridoon, Dumisani Mnkandhla, Michelle Isaacs, Heinrich C Hoppe, Perry T Kaye
A series of readily accessible 4-arylimino-3-hydroxybutanoic acids have been prepared and evaluated as potential HIV-1 Integrase inhibitors. None of the ligands exhibited significant toxicity against human embryonic kidney (HEK 293) cells, while five of them showed activity against HIV-1 integrase - the most active (6c) with an IC50 value of 3.5 μM. In silico docking studies indicate the capacity of ligand 6c to interact with several amino acid residues and the two Mg2+ cations in the HIV-1 integrase receptor cavity...
February 12, 2018: Bioorganic & Medicinal Chemistry Letters
Longping Li, Xin Zhao
BACKGROUND: Integrons are mobile DNA elements and they have an important role in acquisition and dissemination of antimicrobial resistance genes. However, there are limited data available on integrons of Staphylococcus aureus (S. aureus) from bovine mastitis, especially from Chinese dairy cows. To address this knowledge gap, bovine mastitis-inducing S. aureus isolates were investigated for the presence of integrons as well as characterization of gene cassettes. Integrons were detected using PCR reactions and then further characterized by a restriction fragment-length polymorphism analysis and amplicon sequencing...
February 27, 2018: BMC Veterinary Research
Sally Hodder, Kathleen Squires, Cissy Kityo, Debbie Hagins, Anchalee Avihingsanon, Anna Kido, Shuping Jiang, Rima Kulkarni, Andrew Cheng, Huyen Cao
BACKGROUND: The integrase inhibitor regimen (elvitegravir [EVG]/cobicistat [COBI]/emtricitabine [FTC]/tenofovir disoproxil fumarate [TDF]) demonstrated superior efficacy when compared to a protease inhibitor regimen (ritonavir-boosted atazanavir [ATV+RTV] plus FTC/TDF) in 575 treatment-naïve women at week 48. We investigated the efficacy, safety, and tolerability of switching to a TAF-based, single-tablet regimen containing EVG, COBI, FTC, and tenofovir alafenamide TAF (E/C/F/TAF) versus remaining on ATV+RTV and FTC/TDF...
February 21, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Yan Cheng, Nancy A Nickman, Christine Jamjian, Vanessa Stevens, Yue Zhang, Brian Sauer, Joanne LaFleur
Previous studies suggested that human immunodeficiency virus (HIV) infected patients at risk of poor adherence were not distinguishable only based on the baseline characteristics. This study is to identify patient characteristics that would be consistently associated with poor adherence across regimens and to understand the associations between initial and long-term adherence. HIV treatment-naïve patients initiated on protease inhibitors, nonnucleoside reverse transcriptase inhibitors, or integrase strand transfer inhibitors were identified from the Veteran Health Administration system...
January 2018: Medicine (Baltimore)
Yan Cheng, Brian Sauer, Yue Zhang, Nancy A Nickman, Christine Jamjian, Vanessa Stevens, Joanne LaFleur
Many studies have estimated the association between the adherence to antiretroviral therapies and human immunodeficiency virus (HIV) patients' virologic/immunologic outcomes. However, evidence is lacking on the causal effect of adherence on the outcomes. The goal of this study is to understand whether near perfect adherence is necessary to achieve optimal virologic outcome and also to investigate the effect of initial adherence to antiretroviral therapies on initial viral suppression by different regimens. A cohort study was conducted on HIV veterans initiating antiretroviral therapies in 1999 to 2015...
January 2018: Medicine (Baltimore)
A Promsong, T Chuenchitra, K Saipin, S Tewtrakul, P Panichayupakaranant, S Satthakarn, W Nittayananta
OBJECTIVE: To investigate the in vitro effects of ellagic acid on HIV-1 replication. METHODS: Anti-HIV-1 activity of ellagic acid was determined in vitro using X4-tropic HIV-1NPO 3 and R5-tropic pBaL Env-recombinant virus. Anti-HIV-1NPO 3 activity of ellagic acid was investigated at a multiplicity of infection (MOI) of 0.01. Anti-HIV-1 integrase and protease activities of ellagic acid were tested using in vitro integration and proteolytic cleavage assays. RESULTS: Ellagic acid, added either before or after HIV-1NPO 3 exposure, suppressed replication of the virus in C8166 cells up to 34%...
March 2018: Oral Diseases
Kelly A Curtis, Daphne Morrison, Donna L Rudolph, Anupama Shankar, Laura S P Bloomfield, William M Switzer, S Michele Owen
Isothermal nucleic acid amplification techniques, such as reverse-transcription loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are suitable for the development of a rapid, low-cost NAT that can be used at the POC. For demonstration of utility for global use, studies are needed to validate the performance of RT-LAMP for the detection of divergent subtypes. In this study, we designed and evaluated multiplexed HIV-1 integrase RT-LAMP primers to detect subtypes within group M, along with an RNase P positive internal processing and amplification control...
February 20, 2018: Journal of Virological Methods
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