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https://www.readbyqxmd.com/read/28641707/analysis-of-transmitted-hiv-drug-resistance-from-2005-to-2015-in-victoria-australia-a-comparison-of-the-old-and-the-new
#1
Jodie D'Costa, Megan Gooey, Nicole Richards, Rizmina Sameer, Elaine Lee, Doris Chibo
Background: Baseline genotyping is part of standard-of-care treatment. It reveals that transmitted drug resistance (TDR) continues to be important for the management of HIV infection. Attention is typically focused on determining whether resistance to the protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) occurs. However, the increasing use of integrase inhibitors (INIs) raises a concern that TDR to this class of antiretroviral drug may also occur. Methods: PI and RTI drug resistance genotyping was performed on blood samples collected between 2005 and 2015 from 772 treatment-naïve Victorian patients infected with HIV within the previous 12 months...
June 23, 2017: Sexual Health
https://www.readbyqxmd.com/read/28641512/molecular-docking-and-molecular-dynamics-simulation-based-approach-to-explore-the-dual-inhibitor-against-hiv-1-reverse-transcriptase-and-integrase
#2
Subhash Chander, Rajan Kumar Pandey, Ashok Penta, Bhanwar Singh Choudhary, Manish Sharma, Ruchi Malik, Vijay Kumar Prajapati, Sankaranarayanan Murugesan
HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT share the striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. Therefore, the search of compounds with dual inhibition of IN and RNase H can be the viable and more efficacious approach for the drug development against both wild and drug resistance strains of HIV...
June 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28641311/characterisation-of-blood-derived-exosomal-htert-mrna-secretion-in-cancer-patients-a-potential-pan-cancer-marker
#3
Hadar Goldvaser, Anna Gutkin, Einat Beery, Yonatan Edel, Jardena Nordenberg, Ofir Wolach, Ester Rabizadeh, Orit Uziel, Meir Lahav
BACKGROUND: Telomerase (human telomerase reverse transcriptase (hTERT)) is considered a hallmark of cancer. The aim of our study was to evaluate the feasibility of the detection of hTERT transcripts in serum as a 'pan-cancer' diagnostic method. METHODS: Human telomerase reverse transcriptase mRNA levels were determined in serum and serum-derived exosomes from 133 patients with different malignancies and 45 healthy controls. In four patients hTERT mRNA levels were measured in different clinical stages...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28640876/reliability-and-performance-of-commercial-rna-and-dna-extraction-kits-for-ffpe-tissue-cores
#4
Palak G Patel, Shamini Selvarajah, Karl-Philippe Guérard, John M S Bartlett, Jacques Lapointe, David M Berman, John B A Okello, Paul C Park
Cancer biomarker studies often require nucleic acid extraction from limited amounts of formalin-fixed, paraffin-embedded (FFPE) tissues, such as histologic sections or needle cores. A major challenge is low quantity and quality of extracted nucleic acids, which can limit our ability to perform genetic analyses, and have a significant influence on overall study design. This study was aimed at identifying the most reliable and reproducible method of obtaining sufficient high-quality nucleic acids from FFPE tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28639897/gene-signature-based-on-degradome-related-genes-can-predict-distal-metastasis-in-cervical-cancer-patients
#5
Jorge Fernandez-Retana, Horacio Zamudio-Meza, Miguel Rodriguez-Morales, Abraham Pedroza-Torres, David Isla-Ortiz, Luis Herrera, Nadia Jacobo-Herrera, Oscar Peralta-Zaragoza, César López-Camarillo, Fermin Morales-Gonzalez, David Cantu de Leon, Carlos Pérez-Plasencia
Cervical cancer is one of the leading causes of death in women worldwide, which mainly affects developing countries. The patients who suffer a recurrence and/or progression disease have a higher risk of developing distal metastases. Proteases comprising the degradome given its ability to promote cell growth, migration, and invasion of tissues play an important role during tumor development and progression. In this study, we used high-density microarrays and quantitative reverse transcriptase polymerase chain reaction to evaluate the degradome profile and their inhibitors in 112 samples of patients diagnosed with locally advanced cervical cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638390/characterization-genomic-organization-abundance-and-chromosomal-distribution-of-ty1-copia-retrotransposons-in-erianthus-arundinaceus
#6
Yongji Huang, Ling Luo, Xuguang Hu, Fan Yu, Yongqing Yang, Zuhu Deng, Jiayun Wu, Rukai Chen, Muqing Zhang
Erianthus arundinaceus is an important wild species of the genus Saccharum with many valuable traits. However, the composition and structure of its genome are largely unknown, which have hindered its utilization in sugarcane breeding and evolutionary research. Retrotransposons constitute an appreciable fraction of plant genomes and may have played a significant role in the evolution and sequence organization of genomes. In the current study, we investigate the phylogenetic diversity and genomic abundance of Ty1-copia retrotransposons for the first time and inspect their chromosomal distribution patterns in E...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28637362/spindle-cell-mucoepidermoid-carcinoma-of-the-palatine-tonsil-with-crtc1-maml2-fusion-transcript-report-of-a-rare-case-in-a-17-year-old-boy-and-a-review-of-the-literature
#7
Giap Hean Goh, Chwee Ming Lim, Tomas Vanacek, Michal Michal, Fredrik Petersson
Mucoepidermoid carcinoma (MEC) with a predominant spindle cell composition occurring in the palatine tonsil is exceedingly rare. We present a case of a 17-year-old boy with an uncommon spindle cell variant of MEC arising in the palatine tonsil. Histologically, the tumor showed a solid, noncystic architecture and was composed of a predominant population of bland spindle to fusiform cells arranged in organoid nests with interspersed goblet cells and focal areas of ductular structures. Reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed the presence of a t(11;19) CRTC1-MAML2 gene fusion in this rare variant of MEC...
June 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28637198/multi-target-activity-of-hemidesmus-indicus-decoction-against-innovative-hiv-1-drug-targets-and-characterization-of-lupeol-mode-of-action
#8
Francesca Esposito, Manuela Mandrone, Claudia Del Vecchio, Ilaria Carli, Simona Distinto, Angela Corona, Mariacaterina Lianza, Dario Piano, Massimo Tacchini, Elias Maccioni, Filippo Cottiglia, Elisa Saccon, Ferruccio Poli, Cristina Parolin, Enzo Tramontano
Despite the availability of several anti-retrovirals there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors...
June 20, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#9
Nikenza Viceconte, Marie-Sophie Dheur, Eva Majerova, Christophe E Pierreux, Jean-François Baurain, Nicolas van Baren, Anabelle Decottignies
Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636855/efficacy-of-recombinant-influenza-vaccine-in-adults-50-years-of-age-or-older
#10
Lisa M Dunkle, Ruvim Izikson, Peter Patriarca, Karen L Goldenthal, Derek Muse, Janice Callahan, Manon M J Cox
BACKGROUND: Improved influenza vaccines are needed to control seasonal epidemics. This trial compared the protective efficacy in older adults of a quadrivalent, recombinant influenza vaccine (RIV4) with a standard-dose, egg-grown, quadrivalent, inactivated influenza vaccine (IIV4) during the A/H3N2-predominant 2014-2015 influenza season, when antigenic mismatch between circulating and vaccine influenza strains resulted in the reduced effectiveness of many licensed vaccines. METHODS: We conducted a randomized, double-blind, multicenter trial of RIV4 (45 μg of recombinant hemagglutinin [HA] per strain, 180 μg of protein per dose) versus standard-dose IIV4 (15 μg of HA per strain, 60 μg of protein per dose) to compare the relative vaccine efficacy against reverse-transcriptase polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined, influenza-like illness caused by any influenza strain starting 14 days or more after vaccination in adults who were 50 years of age or older...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28631290/a-h2-oxidizing-1-2-3-trichlorobenzene-reducing-multienzyme-complex-isolated-from-the-obligately-organohalide-respiring-bacterium-dehalococcoides-mccartyi-strain-cbdb1
#11
Stefanie Hartwig, Nadya Dragomirova, Anja Kublik, Dominique Türkowsky, Martin von Bergen, Ute Lechner, Lorenz Adrian, R Gary Sawers
Dehalococcoides mccartyi is a small, slow-growing bacterium of the phylum Chloroflexi that conserves energy using aliphatic and aromatic organohalides as electron acceptors, and hydrogen as sole electron donor. A recent study identified a protein complex in the membrane of strain CBDB1 comprising a Hup hydrogenase, a complex iron-sulphur molybdoprotein and a reductive dehalogenase (RdhA) that catalyses reduction of 1,2,3,4-tetrachlorobenzene. Using a combination of size-exclusion chromatography, in-gel hydrogenase activity-staining, immunological analysis and mass spectrometry, we identified here a large molecular mass protein complex solubilized from the cytoplasmic membrane of D...
June 19, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28630939/retrospective-surveillance-of-wastewater-to-examine-seasonal-dynamics-of-enterovirus-infections
#12
Nichole E Brinkman, G Shay Fout, Scott P Keely
Enteroviruses are RNA viruses that are responsible for both mild gastroenteritis and mild respiratory illnesses as well as debilitating diseases such as meningitis and myocarditis. The disease burden of enteroviruses in the United States is difficult to assess because most infections are not recorded. Since infected individuals shed enterovirus in feces and urine, surveillance of municipal wastewater can reveal the diversity of enteroviruses circulating in human populations. Therefore, monthly municipal wastewater samples were collected for 1 year and enteroviruses were quantified by reverse transcriptase quantitative PCR and identified by next-generation, high-throughput sequencing...
May 2017: MSphere
https://www.readbyqxmd.com/read/28628667/characterization-of-hiv-1-crf90_bf1-and-putative-novel-crfs_bf1-in-central-west-north-and-northeast-brazilian-regions
#13
Mônica Nogueira da Guarda Reis, Gonzalo Bello, Monick Lindenmeyer Guimarães, Mariane Martins Araújo Stefani
The Brazilian AIDS epidemic has been characterized by an increasing rate of BF1 recombinants and so far eight circulating recombinant forms/CRFs_BF1 have been described countrywide. In this study, pol sequences (protease/PR, reverse transcriptase/RT) of 87 BF1 mosaic isolates identified among 828 patients living in six Brazilian States from three geographic regions (Central West, North, Northeast) were analyzed. Phylogenetic and bootscan analyses were performed to investigate the evolutionary relationship and mosaic structure of BF1 isolates...
2017: PloS One
https://www.readbyqxmd.com/read/28628529/appraising-viral-load-thresholds-and-adherence-support-recommendations-in-the-world-health-organization-guidelines-for-detection-and-management-of-virologic-failure
#14
Suzanne M McCluskey, Yap Boum, Nicholas Musinguzi, Jessica E Haberer, Jeffrey N Martin, Peter W Hunt, Vincent C Marconi, David R Bangsberg, Mark J Siedner
BACKGROUND: The World Health Organization defines HIV virologic failure as two consecutive viral loads >1,000 copies/mL, measured 3-6 months apart with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort. SETTING: The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation, and monitored adherence with electronic pill bottles...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28628528/increased-persistence-of-initial-treatment-for-hiv-infection-with-modern-antiretroviral-therapy
#15
Thibaut Davy-Mendez, Joseph J Eron, Oksana Zakharova, David A Wohl, Sonia Napravnik
BACKGROUND: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic response to initial ART according to the class of anchor agent used. SETTING: An observational clinical cohort study in the Southeastern United States. METHODS: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28628334/chiral-indolylarylsulfone-non-nucleoside-reverse-transcriptase-inhibitors-as-new-potent-and-broad-spectrum-anti-hiv-1-agents
#16
Valeria Famiglini, Giuseppe La Regina, Antonio Coluccia, Domiziana Masci, Andrea Brancale, Roger Badia, Eva Riveira Muñoz, Jose A Este, Emmanuele Crespan, Alessandro Brambilla, Giovanni Maga, Myriam Catalano, Cristina Limatola, Francesca Romana Romana Formica, Roberto Cirilli, Ettore Novellino, Romano Silvestri
We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L and K103N-Y181C HIV-1 strains. Six racemic mixtures, 8, 23-25, 31 and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31 and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers...
June 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28628279/acyclic-nucleoside-phosphonates-containing-9-deazahypoxanthine-and-a-5-membered-heterocycle-as-selective-inhibitors-of-plasmodial-6-oxopurine-phosphoribosyltransferases
#17
Martin Maxmilian Kaiser, Ondřej Baszczyňski, Dana Hocková, Lenka Poštová-Slavětínská, Martin Dračínský, Dianne T Keough, Luke W Guddat, Zlatko Janeba
Acyclic nucleoside phosphonates (ANPs) are an important class of therapeutic drugs that act as antiviral agents by inhibiting viral DNA polymerases and reverse transcriptases. ANPs containing a 6-oxopurine instead of 6-aminopurine or pyrimidine bases are inhibitors of the purine salvage enzyme, hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase (HG[X]PRT). Such compounds, and their prodrugs, are able to arrest the growth of Plasmodium falciparum (Pf) in cell culture. A new series of ANPs has been synthesized and tested as inhibitors of human HGPRT, PfHGXPRT and Plasmodium vivax (Pv) HGPRT...
June 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28627823/hepatitis-c-an-overview-of-various-laboratory-assays-with-their-mode-of-diagnostic-cooperation
#18
REVIEW
Mohammad-Ayman A Safi
BACKGROUND: This review describes in chronological order the different assays for hepatitis C virus (HCV) antibodies, for the core antigen and for the HCV-RNA. METHODS: By ascending chronological order, the enzyme-linked immunosorbent assay (ELISA), rapid diagnostic tests (RDTs), HCV-Ab IgG avidity index (HCV AI), and Cy3-labeled microarray assay have been described for HCV antibodies in addition to ELISA for the total HCV core antigen (Ag). RESULTS: The recombinant immunoblot assay (RIBA) is a confirmatory test for HCV-Ab in blood, which is no longer needed due to the use of the sensitive third and fourth generation ELISA in addition to HCV-RNA detection by the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28627695/targeted-cdx2-expression-inhibits-aggressive-phenotypes-of-colon-cancer-cells-in-vitro-and-in-vivo
#19
Jianbao Zheng, Sai He, Jie Qi, Xiaolong Wang, Junhui Yu, Yunhua Wu, Qi Gao, Kai Wang, Xuejun Sun
Loss of caudal type homeobox 2 (CDX2) is associated with the development of human colorectal cancer, while human telomerase reverse transcriptase (hTERT) frequently occurs in variety of human cancers. We investigated the effects of restoration of CDX2 expression using a hypoxia-inducible hTERT promoter-driven vector (pLVX-5HRE-hTERTp-CDX2-3FLAG) on colon cancer cell viability, cell cycle distribution, apoptosis, colony formation, invasion ability and xenograft tumor growth in nude mice. CDX2 overexpression significantly inhibited viability, colony formation, and the invasion and migration ability of LoVo cells, and induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions...
June 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28627628/phosphorothioate%C3%A2-modified-antisense-oligonucleotides-against-human-telomerase-reverse-transcriptase-sensitize-cancer-cells-to-radiotherapy
#20
Fei Cao, Xiaoping Ju, Di Chen, Lingong Jiang, Xiaofei Zhu, Shuiwang Qing, Fang Fang, Yuxin Shen, Zhen Jia, Huojun Zhang
Emergence of resistance, unavoidable systemic toxicity and unsatisfactory efficacy arethe main obstacles for traditional cancer therapy. Combination with phosphorothioate modified antisense oligonucleotides (PS‑ASODN) against human telomerase reverse transcriptase (hTERT) may enhance the therapeutic effect of irradiation. However, the effect of PS‑ASODN against hTERT on the anti‑tumor effects of irradiation in liver cancer remain unclear. In the current study, Walker 256 cells were transfected with hTERT PS‑ASODN...
June 14, 2017: Molecular Medicine Reports
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