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https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#1
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28815509/production-of-minicircle-dna-vectors-using-site-specific-recombinases
#2
Nafiseh Sanei Ata-Abadi, Naeimeh Rezaei, Kianoush Dormiani, Mohammad Hossein Nasr-Esfahani
Minicircle DNA vectors are plasmid derivatives free of bacterial elements. These vectors are mostly provided from common plasmids via recombination by site-specific recombinases in E. coli. Absence of bacterial backbone in minicircle vectors results in high-level and persistent expression of transgene in comparison with conventional plasmids and provides promising vehicles for gene therapy and vaccination. Here we describe the production of replicative minicircle DNA vectors using the PBAD/araC system expressing ΦC31 integrase in E...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815508/multipart-dna-assembly-using-site-specific-recombinases-from-the-large-serine-integrase-family
#3
Femi J Olorunniji, Christine Merrick, Susan J Rosser, Margaret C M Smith, W Marshall Stark, Sean D Colloms
Assembling multiple DNA fragments into functional plasmids is an important and often rate-limiting step in engineering new functions in living systems. Bacteriophage integrases are enzymes that carry out efficient recombination reactions between short, defined DNA sequences known as att sites. These DNA splicing reactions can be used to assemble large numbers of DNA fragments into a functional circular plasmid in a method termed serine integrase recombinational assembly (SIRA). The resulting DNA assemblies can easily be modified by further recombination reactions catalyzed by the same integrase in the presence of its recombination directionality factor (RDF)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815494/use-of-the-dice-dual-integrase-cassette-exchange-system
#4
Alfonso P Farruggio, Mital S Bhakta, Michele P Calos
When constructing transgenic cell lines via plasmid DNA integration, precise targeting to a desired genomic location is advantageous. It is also often advantageous to remove the bacterial backbone, since bacterial elements can lead to the epigenetic silencing of neighboring DNA. The least cumbersome method to remove the plasmid backbone is recombinase-mediated cassette exchange (RMCE). RMCE is accomplished by arranging recombinase sites in the genome and in a donor plasmid such that a recombinase can both integrate the donor plasmid and excise its bacterial backbone...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28814231/hiv-type-1-integrase-natural-polymorphisms-in-viral-variants-circulating-in-fsu-countries
#5
Ilya Lapovok, Vita Laga, Elena Kazennova, Marina Bobkova
BACKGROUND: Natural variability of integrase (IN) across HIV-1 variants may influence the emergence of resistant viruses. The most apparent explanation of these fact is the IN polymorphism and the associated differences in codon usage, which, in turn, influence the probability and the terms of DRMs acquisition. Possible mechanisms by which polymorphisms affect DRMs emergence remain disputed and should still be clarified because these substitutions may be associated with a reduced activity of some INSTIs and may impact on ART regimen choice depending of HIV-1 subtype...
August 15, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28807850/anti-hiv-activity-of-southern-african-plants-current-developments-phytochemistry-and-future-research
#6
REVIEW
Gerhard Prinsloo, Cynthia K Marokane, Renée A Street
ETHNOPHARMACOLOGICAL RELEVANCE: The African continent is home to a large number of higher plant species used over centuries for many applications, which include treating and managing diseases such as HIV. Due to the overwhelming prevalence and incidence rates of HIV, especially in sub-Saharan Africa, it is necessary to develop new and affordable treatments. AIM OF THE STUDY: The article provides an extensive overview of the status on investigation of plants from the southern African region with ethnobotanical use for treating HIV or HIV-related symptoms, or the management of HIV...
August 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28806198/pre-treatment-integrase-strand-transfer-inhibitor-resistance-in-north-carolina-from-2010-2016
#7
Timothy W Menza, Rachael Billock, Erika Samoff, Joseph J Eron, Ann M Dennis
OBJECTIVE: We sought to define the prevalence of pre-treatment INSTI resistance and assess the transmission networks of those with pre-treatment INSTI resistance. DESIGN: A retrospective cohort study of HIV-positive patients with genotypic resistance testing sent to a single referral laboratory in North Carolina between 2010 and 2016. METHODS: We linked genotype and public health data for in-care HIV-positive individuals to determine the prevalence of INSTI resistance among treatment-naïve (defined as those with a first genotype ≤3 months after diagnosis) and treatment-experienced (defined as those with a first genotype >3 months after diagnosis) patients...
August 12, 2017: AIDS
https://www.readbyqxmd.com/read/28805638/nonretroviral-integrated-rna-viruses-in-arthropod-vectors-an-occasional-event-or-something-more
#8
REVIEW
Ken E Olson, Mariangela Bonizzoni
With few exceptions, all arthropod-borne viruses (arboviruses) are nonretroviral RNA viruses (NRVs). Despite NRVs do not encode reverse transcriptases and integrases, NRVs-DNA fragments are detected in mosquito cells and mosquitoes at early stages of infection as episomal DNA forms. Additionally, next generation sequencing and bioinformatics analyses have convincingly shown NRVs-vDNA integrated in vector genomes. We hypothesize vDNA role may be linked to host immunity and viral persistence. Key questions remain about nonretroviral integrated RNA virus sequences (NIRVS) in mosquitoes such as what is driving vDNA synthesis from NRVs, how does integration occur and what is their biological function...
August 2017: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/28804720/integron-mediated-antibiotic-resistance-in-acinetobacter-baumannii-isolated-from-intensive-care-unit-patients-babol-north-of-iran
#9
Mitra Deylam Salehi, Elaheh Ferdosi-Shahandashti, Yosef Yahyapour, Soraya Khafri, Abazar Pournajaf, Ramazan Rajabnia
BACKGROUND: We investigated the integron types and their relation with antibiotic resistance among A. baumannii isolates collected from intensive care unit patients, Babol, north of Iran. METHODS: In this cross-sectional study, a total of 73 bronchoalveolar lavage samples were obtained from patients in ICU. Susceptibility testing was performed by disk diffusion method. Types of integrons were identified by an integrase gene PCR. RESULTS: In total, 47...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28802644/rapid-characterization-of-the-cho-platform-cell-line-and-identification-of-pseudo-attp-sites-for-phic31-integrase
#10
Narges Damavandi, Mozhgan Raigani, Atefeh Joudaki, Fatemeh Davami, Sirous Zeinali
The Chinese Hamster Ovary (CHO) cell lines, applicable to post-translational modifications, are preferred systems for biopharmaceutical protein production. In this study, by using the Jump-In™ TI™ technology which employs PhiC31 and R4 bacteriophage recombinases, a platform CHO-K1 cell line containing a R4-attP site was generated. Here, a combination of Quantitative Fluorescent-Polymerase Chain Reaction (QF-PCR) and semi-random, two-step PCR (ST-PCR), was performed to feature the platform cell clones. Our results show that QF-PCR and ST-PCR, can be utilized for efficient and accelerated cell line characterization...
August 9, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28799737/method-to-assemble-genomic-dna-fragments-or-genes-on-human-artificial-chromosome-with-regulated-kinetochore-using-a-multi-integrase-system
#11
Nicholas C O Lee, Jung-Hyun Kim, Nikolai Petrov, Hee-Sheung Lee, Hiroshi Masumoto, William C Earnshaw, Vladimir Larionov, Natalay Kouprina
The production of cells capable of carrying multiple transgenes to Mb-size genomic loci has multiple applications in biomedicine and biotechnology. In order to achieve this goal, three key steps are required: i) Cloning of large genomic segments; ii) Insertion of multiple DNA blocks at a precise location and iii) The capability to eliminate the assembled region from cells. In this study, we designed the Iterative Integration System (IIS) that utilizes recombinases Cre, ΦC31 and ΦBT1, and combined it with Human Artificial Chromosome (HAC) possessing a regulated kinetochore (alphoid(tetO)-HAC)...
August 11, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28798737/complete-genome-analysis-of-thermus-parvatiensis-and-comparative-genomics-of-thermus-spp-provide-insights-into-genetic-variability-and-evolution-of-natural-competence-as-strategic-survival-attributes
#12
Charu Tripathi, Harshita Mishra, Himani Khurana, Vatsala Dwivedi, Komal Kamra, Ram K Negi, Rup Lal
Thermophilic environments represent an interesting niche. Among thermophiles, the genus Thermus is among the most studied genera. In this study, we have sequenced the genome of Thermus parvatiensis strain RL, a thermophile isolated from Himalayan hot water springs (temperature >96°C) using PacBio RSII SMRT technique. The small genome (2.01 Mbp) comprises a chromosome (1.87 Mbp) and a plasmid (143 Kbp), designated in this study as pTP143. Annotation revealed a high number of repair genes, a squeezed genome but containing highly plastic plasmid with transposases, integrases, mobile elements and hypothetical proteins (44%)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28797965/fate-of-antibiotic-resistance-genes-in-mesophilic-and-thermophilic-anaerobic-digestion-of-chemically-enhanced-primary-treatment-cept-sludge
#13
Hyun Min Jang, Jingyeong Shin, Sangki Choi, Seung Gu Shin, Ki Young Park, Jinwoo Cho, Young Mo Kim
Anaerobic digestion (AD) of chemically enhanced primary treatment (CEPT) sludge and non-CEPT (conventional sedimentation) sludge were comparatively operated under mesophilic and thermophilic conditions. The highest methane yield (692.46±0.46mL CH4/g VSremoved in CEPT sludge) was observed in mesophilic AD of CEPT sludge. Meanwhile, thermophilic conditions were more favorable for the removal of total antibiotic resistance genes (ARGs). In this study, no measurable difference in the fates and removal of ARGs and class 1 integrin-integrase gene (intI1) was observed between treated non-CEPT and CEPT sludge...
July 29, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28793863/cardiovascular-risk-and-dyslipidemia-among-persons-living-with-hiv-a-review
#14
REVIEW
Paolo Maggi, Antonio Di Biagio, Stefano Rusconi, Stefania Cicalini, Maurizio D'Abbraccio, Gabriella d'Ettorre, Canio Martinelli, Giuseppe Nunnari, Laura Sighinolfi, Vincenzo Spagnuolo, Nicola Squillace
BACKGROUND: Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? DISCUSSION: Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments...
August 9, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28792642/wastewater-pollution-differently-affects-the-antibiotic-resistance-gene-pool-and-biofilm-bacterial-communities-across-streambed-compartments
#15
Jèssica Subirats, Xavier Triadó-Margarit, Ladislav Mandaric, Vicenç Acuña, José Luis Balcázar, Sergi Sabater, Carles M Borrego
Wastewater discharges introduce antibiotic residues and antibiotic-resistant bacteria (ARB) into surface waters. Both inputs directly affect the streambed resistome, either by exerting a selective pressure that favor the proliferation of resistant phenotypes or by enriching the resident communities with wastewater-associated ARB. Here, we investigated the impact of raw and treated urban wastewater discharges on epilithic (growing on rocks) and epipsammic (growing on sandy substrata) streambed biofilms. The effects were assessed by comparing control and impact sites i) on the composition of bacterial communities; ii) on the abundance of twelve antibiotic resistance genes (ARGs) encoding resistance to β-lactams, fluoroquinolones, sulfonamides, tetracyclines, macrolides and vancomycin, as well as the class 1 integron-integrase gene (intI1); and iii) on the occurrence of wastewater-associated bacteria, including putative pathogens, and their potential linkage to target ARGs...
August 9, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28790862/hyperbilirubinemia-in-atazanavir-treated-hiv-infected-patients-the-impact-of-the-ugt1a1-28-allele
#16
REVIEW
Periklis Panagopoulos, Efstathios Maltezos, Angelos Hatzakis, Dimitrios Paraskevis
Combination antiretroviral treatment (cART) has significantly improved the life expectancy of people living with HIV. The life-long nature of cART increases the risk of side effects, which in some cases may have been caused by specific genetic characteristics. Patients treated with atazanavir (ATV) boosted with ritonavir (rit), which is a protease inhibitor used for the treatment of HIV, present with elevated bilirubin levels, at high proportions. ATV/rit-related hyperbilirubinemia has been previously associated with genetic characteristics in uridine diphosphate glucuronosyltransferase (UGT) enzyme...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28783909/an-underappreciated-hotspot-of-antibiotic-resistance-the-groundwater-near-the-municipal-solid-waste-landfill
#17
Qing-Lin Chen, Hu Li, Xin-Yuan Zhou, Yi Zhao, Jian-Qiang Su, Xian Zhang, Fu-Yi Huang
Landfills are so far the most common practice for the disposals of municipal solid waste (MSW) worldwide. Since MSW landfill receives miscellaneous wastes, including unused/expired antibiotics and bioactive wastes, it gradually becomes a huge potential bioreactor for breeding antibiotic resistance. Antibiotic resistance genes (ARGs) in landfill can flow to the environment through leakage of landfill leachate and pose a risk to public health. Using high throughput quantitative Polymerase Chain Reaction (HT-qPCR), we investigated the prevalence, diversity of ARGs and its association with various mobile genetic elements (MGEs) in MSW landfill groundwater...
July 31, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28780361/untreated-urban-waste-contaminates-indian-river-sediments-with-resistance-genes-to-last-resort-antibiotics
#18
Nachiket P Marathe, Chandan Pal, Swapnil S Gaikwad, Viktor Jonsson, Erik Kristiansson, D G Joakim Larsson
Efficient sewage treatment is critical for limiting environmental transmission of antibiotic-resistant bacteria. In many low and middle income countries, however, large proportions of sewage are still released untreated into receiving water bodies. In-depth knowledge of how such discharges of untreated urban waste influences the environmental resistome is largely lacking. Here, we highlight the impact of uncontrolled discharge of partially treated and/or untreated wastewater on the structure of bacterial communities and resistome of sediments collected from Mutha river flowing through Pune city in India...
July 25, 2017: Water Research
https://www.readbyqxmd.com/read/28762239/high-performance-liquid-chromatography-tandem-mass-spectrometry-for-simultaneous-determination-of-raltegravir-dolutegravir-and-elvitegravir-concentrations-in-human-plasma-and-cerebrospinal-fluid-samples
#19
Kiyoto Tsuchiya, Mayu Ohuchi, Naoe Yamane, Hiroaki Aikawa, Hiroyuki Gatanaga, Shinichi Oka, Akinobu Hamada
A simple sample treatment procedure and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 (HIV-1) integrase strand transfer inhibitors (INSTIs); raltegravir (RAL), dolutegravir (DTG), and elvitegravir (EVG); in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d3 was used as the internal standard (IS)...
July 31, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28754126/modulation-of-chromatin-structure-by-the-fact-histone-chaperone-complex-regulates-hiv-1-integration
#20
Julien Matysiak, Paul Lesbats, Eric Mauro, Delphine Lapaillerie, Jean-William Dupuy, Angelica P Lopez, Mohamed Salah Benleulmi, Christina Calmels, Marie-Line Andreola, Marc Ruff, Manuel Llano, Olivier Delelis, Marc Lavigne, Vincent Parissi
BACKGROUND: Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration...
July 28, 2017: Retrovirology
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