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https://www.readbyqxmd.com/read/28105263/treatment-of-hiv-infections-with-hiv-integrase-inhibitors
#1
EDITORIAL
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28095260/differential-expression-and-roles-of-secreted-frizzled-related-protein-5-and-the-wingless-homolog-wnt5a-in-periodontitis
#2
T Maekawa, P Kulwattanaporn, K Hosur, H Domon, M Oda, Y Terao, T Maeda, G Hajishengallis
The Wingless/integrase-1 (Wnt) family of protein ligands and their functional antagonists, secreted frizzled-related proteins (sFRPs), regulate various biological processes ranging from embryonic development to immunity and inflammation. Wnt5a and sFRP5 comprise a typical ligand/antagonist pair, and the former molecule was recently detected at the messenger RNA (mRNA) level in human periodontitis. The main objective of this study was to investigate the interrelationship of expression of Wnt5a and sFRP5 in human periodontitis (as compared to health) and to determine their roles in inflammation and bone loss in an animal model...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28089931/a-novel-polysaccharide-with-antioxidant-hiv-protease-inhibiting-and-hiv-integrase-inhibiting-activities-from-fomitiporia-punctata-p-karst-murrill-basidiomycota-hymenochaetales
#3
Fang Liu, Yinping Wang, Keren Zhang, Yijun Wang, Rong Zhou, Yan Zeng, Yajie Han, Tzi Bun Ng
A novel polysaccharide fraction (G1) was obtained from the fungus Fomitiporia punctata (P. Karst.) Murrill. G1 exhibited a molecular weight of approximately 151kDa. The FT-IR results suggested that the monosaccharide components of G1 possessed furanoid rings and there were β-glycosidic bonds between the sugar units. The(1)H NMR results showed that G1 was composed of arabinose, fructose, galactose and glucose in the molar ratio of 1.6:3.8:19.7:19.7, as determined by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC)...
January 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28088540/multiplexed-site-specific-genome-engineering-for-overproducing-bioactive-secondary-metabolites-in-actinomycetes
#4
Lei Li, Guosong Zheng, Jun Chen, Mei Ge, Weihong Jiang, Yinhua Lu
Actinomycetes produce a large variety of pharmaceutically active compounds, yet production titers often require to be improved for discovery, development and large-scale manufacturing. Here, we describe a new technique, multiplexed site-specific genome engineering (MSGE) via the 'one integrase-multiple attB sites' concept, for the stable integration of secondary metabolite biosynthetic gene clusters (BGCs). Using MSGE, we achieved five-copy chromosomal integration of the pristinamycin II (PII) BGC in Streptomyces pristinaespiralis, resulting in the highest reported PII titers in flask and batch fermentations (2...
January 11, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28087972/lack-of-effect-of-oral-cabotegravir-on-the-pharmacokinetics-of-a-levonorgestrel-ethinyl-estradiol-containing-oral-contraceptive-in-healthy-adult-females
#5
C Trezza, S L Ford, E Gould, Y Lou, C Huang, J M Ritter, A M Buchanan, W Spreen, P Patel
AIM(S): This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of HIV-1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl estradiol (EE)-containing oral contraceptive (OC) in healthy women. METHODS: In this open-label, fixed-sequence crossover study, healthy female subjects received LNG 0.15 mg/EE 0.03 mg tablet once daily Days 1-10 alone and with oral CAB 30 mg once daily Days 11-21...
January 14, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28086908/hiv-integration-sites-in-latently-infected-cell-lines-evidence-of-ongoing-replication
#6
Jori Symons, Abha Chopra, Eva Malantinkova, Ward De Spiegelaere, Shay Leary, Don Cooper, Chike O Abana, Ajantha Rhodes, Simin D Rezaei, Linos Vandekerckhove, Simon Mallal, Sharon R Lewin, Paul U Cameron
BACKGROUND: Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. RESULTS: We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines...
January 13, 2017: Retrovirology
https://www.readbyqxmd.com/read/28077763/a-simplified-mathematical-model-of-directional-dna-site-specific-recombination-by-serine-integrases
#7
Alexandra Pokhilko, Jia Zhao, W Marshall Stark, Sean D Colloms, Oliver Ebenhöh
Serine integrases catalyse site-specific recombination to integrate and excise bacteriophage genomes into and out of their host's genome. These enzymes exhibit remarkable directionality; in the presence of the integrase alone, recombination between attP and attB DNA sites is efficient and irreversible, giving attL and attR products which do not recombine further. However, in the presence of the bacteriophage-encoded recombination directionality factor (RDF), integrase efficiently promotes recombination between attL and attR to re-form attP and attB The DNA substrates and products of both reactions are approximately isoenergetic, and no cofactors (such as adenosine triphosphate) are required for recombination...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28077588/first-in-human-evaluation-of-the-safety-and-immunogenicity-of-an-intranasally-administered-replication-competent-sendai-virus-vectored-hiv-type-1-gag-vaccine-induction-of-potent-t-cell-or-antibody-responses-in-prime-boost-regimens
#8
Julien Nyombayire, Omu Anzala, Brian Gazzard, Etienne Karita, Philip Bergin, Peter Hayes, Jakub Kopycinski, Gloria Omosa-Manyonyi, Akil Jackson, Jean Bizimana, Bashir Farah, Eddy Sayeed, Christopher L Parks, Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Len Dally, Burc Barin, Harriet Park, Jill Gilmour, Angela Lombardo, Jean-Louis Excler, Patricia Fast, Dagna S Laufer, Josephine H Cox
BACKGROUND:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. METHODS:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28076335/infrequent-development-of-drug-resistance-in-hiv-1-infected-treatment-naive-subjects-after-96-weeks-of-treatment-with-elvitegravir-cobicistat-emtricitabine-tenofovir-alafenamide-or-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate
#9
Nicolas Margot, Stephanie Cox, Moupali Das, Scott McCallister, Michael D Miller, Christian Callebaut
BACKGROUND: Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide RT inhibitor (NtRTI) tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) composed of elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/mL at week 48, and maintained through week 96...
January 11, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28071976/precise-flexible-and-affordable-gene-stacking-for-crop-improvement
#10
Weiqiang Chen, David W Ow
Addendum to: Hou L, Yau YY, Wei J, Han Z, Dong Z, Ow DW. An open-source system for in planta gene stacking by Bxb1 and Cre recombinases. Mol Plant, 2014; 7(12):1756-1765. doi:10.1093/mp/ssu107; Li R, Han Z, Hou L, Kaur G, Yin Q, Ow DW. Method for Biolistic Site-Specific Integration in Plants Catalyzed by Bxb1 Integrase. In: Murata M, editor. Chromosome and Genomic Engineering in Plants: Methods and Protocols, Methods in Molecular Biology. 2016; p.15-30; and Chen W, Ow DW. Protocol for In Vitro Stacked Molecules Compatible with In Vivo Recombinase-Mediated Gene Stacking...
January 10, 2017: Bioengineered
https://www.readbyqxmd.com/read/28070909/peptide-fibrils-as-monomer-storage-of-the-covalent-hiv-1-integrase-inhibitor
#11
Koushik Chandra, Priyadip Das, Norman Metanis, Assaf Friedler, Meital Reches
We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361-370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers...
January 10, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28069884/purification-of-zika-virus-rna-dependent-rna-polymerase-and-its-use-to-identify-small-molecule-zika-inhibitors
#12
Hong-Tao Xu, Said A Hassounah, Susan P Colby-Germinario, Maureen Oliveira, Clare Fogarty, Yudong Quan, Yingshan Han, Olga Golubkov, Ilinca Ibanescu, Bluma Brenner, Brent R Stranix, Mark A Wainberg
BACKGROUND: The viral RNA-dependent RNA polymerase (RdRp) enzymes of the Flaviviridae family are essential for viral replication and are logically important targets for development of antiviral therapeutic agents. Zika virus (ZIKV) is a rapidly re-emerging human pathogen for which no vaccine or antiviral agent is currently available. METHODS: To facilitate development of ZIKV RdRp inhibitors, we have established an RdRp assay using purified recombinant ZIKV NS5 polymerase...
January 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28066922/x-ray-crystal-structure-of-the-n-terminal-region-of-moloney-murine-leukemia-virus-integrase-and-its-implications-for-viral-dna-recognition
#13
Rongjin Guan, Sriram Aiyer, Marie L Cote, Rong Xiao, Mei Jiang, Thomas B Acton, Monica J Roth, Gaetano T Montelione
The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain (CCD), and the C-terminal domain (CTD). The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1-44) and an HHCC zinc-finger NTD (residues 45-105), in two crystal forms are reported...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28061387/the-role-of-zero-valent-iron-on-the-fate-of-tetracycline-resistance-genes-and-class-1-integrons-during-thermophilic-anaerobic-co-digestion-of-waste-sludge-and-kitchen-waste
#14
Pin Gao, Chaochao Gu, Xin Wei, Xiang Li, Hong Chen, Hanzhong Jia, Zhenhong Liu, Gang Xue, Chunyan Ma
Activated sludge has been identified as a potential significant source of antibiotic resistance genes (ARGs) to the environment. Anaerobic digestion is extensively used for sludge stabilization and resource recovery, and represents a crucial process for controlling the dissemination of ARGs prior to land application of digested sludge. The objective of this study is to investigate the effect of zero valent iron (Fe(0)) on the attenuation of seven representative tetracycline resistance genes (tet, tet(A), tet(C), tet(G), tet(M), tet(O), tet(W), and tet(X)), and the integrase gene intI1 during thermophilic anaerobic co-digestion of waste sludge and kitchen waste...
December 27, 2016: Water Research
https://www.readbyqxmd.com/read/28059770/a-supramolecular-assembly-mediates-lentiviral-dna-integration
#15
Allison Ballandras-Colas, Daniel P Maskell, Erik Serrao, Julia Locke, Paolo Swuec, Stefán R Jónsson, Abhay Kotecha, Nicola J Cook, Valerie E Pye, Ian A Taylor, Valgerdur Andrésdóttir, Alan N Engelman, Alessandro Costa, Peter Cherepanov
Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo-electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28059769/cryo-em-structures-and-atomic-model-of-the-hiv-1-strand-transfer-complex-intasome
#16
Dario Oliveira Passos, Min Li, Renbin Yang, Stephanie V Rebensburg, Rodolfo Ghirlando, Youngmin Jeon, Nikoloz Shkriabai, Mamuka Kvaratskhelia, Robert Craigie, Dmitry Lyumkis
Like all retroviruses, HIV-1 irreversibly inserts a viral DNA (vDNA) copy of its RNA genome into host target DNA (tDNA). The intasome, a higher-order nucleoprotein complex composed of viral integrase (IN) and the ends of linear vDNA, mediates integration. Productive integration into host chromatin results in the formation of the strand transfer complex (STC) containing catalytically joined vDNA and tDNA. HIV-1 intasomes have been refractory to high-resolution structural studies. We used a soluble IN fusion protein to facilitate structural studies, through which we present a high-resolution cryo-electron microscopy (cryo-EM) structure of the core tetrameric HIV-1 STC and a higher-order form that adopts carboxyl-terminal domain rearrangements...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28053842/rapid-molecular-approach-for-simultaneous-detection-of-salmonella-spp-shigella-spp-and-vibrio-cholera
#17
Reza Ranjbar, Ali Naghoni, Davoud Afshar, Farhad Nikkhahi, Mohsen Mohammadi
OBJECTIVES: Gastrointestinal tract infection is still one of the serious public health problems in many geographic areas and is endemic in most countries including Iran. Early detection of the gastrointestinal tract pathogens can be extremely important. The aim of the current study was to apply a shortened time-multiplex polymerase chain reaction (PCR) for rapid and simultaneous detection of Salmonella spp., Shigella spp., and Vibrio cholera. METHODS: The standard and clinical strains of Salmonella spp...
December 2016: Osong Public Health and Research Perspectives
https://www.readbyqxmd.com/read/28053117/gb3-0-a-platform-for-plant-bio-design-that-connects-functional-dna-elements-with-associated-biological-data
#18
Marta Vazquez-Vilar, Alfredo Quijano-Rubio, Asun Fernandez-Del-Carmen, Alejandro Sarrion-Perdigones, Rocio Ochoa-Fernandez, Peio Ziarsolo, José Blanca, Antonio Granell, Diego Orzaez
Modular DNA assembly simplifies multigene engineering in Plant Synthetic Biology. Furthermore, the recent adoption of a common syntax to facilitate the exchange of plant DNA parts (phytobricks) is a promising strategy to speed up genetic engineering. Following this lead, here, we present a platform for plant biodesign that incorporates functional descriptions of phytobricks obtained under pre-defined experimental conditions, and systematically registers the resulting information as metadata for documentation...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28035758/genotypic-tropism-testing-of-proviral-dna-to-guide-maraviroc-initiation-in-aviraemic-subjects-48-week-analysis-of-results-from-the-protest-study
#19
E Poveda, J Hernández-Quero, M J Pérez-Elías, M A Ribas, O J Martínez-Madrid, J Flores, J Navarro, F Gutiérrez, M García-Deltoro, A Imaz, A Ocampo, A Artero, F Blanco, E Bernal, J Pasquau, C Mínguez-Gallego, N Pérez, A Aiestaran, F García, R Paredes
OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks...
December 30, 2016: HIV Medicine
https://www.readbyqxmd.com/read/28034956/dna-binding-specificities-of-escherichia-coli-cas1-cas2-integrase-drive-its-recruitment-at-the-crispr-locus
#20
Clara Moch, Michel Fromant, Sylvain Blanquet, Pierre Plateau
Prokaryotic adaptive immunity relies on the capture of fragments of invader DNA (protospacers) followed by their recombination at a dedicated acceptor DNA locus. This integrative mechanism, called adaptation, needs both Cas1 and Cas2 proteins. Here, we studied in vitro the binding of an Escherichia coli Cas1-Cas2 complex to various protospacer and acceptor DNA molecules. We show that, to form a long-lived ternary complex containing Cas1-Cas2, the acceptor DNA must carry a CRISPR locus, and the protospacer must not contain 3'-single-stranded overhangs longer than 5 bases...
December 29, 2016: Nucleic Acids Research
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