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https://www.readbyqxmd.com/read/27933889/next-generation-reduction-sensitive-lipid-conjugates-of-tenofovir-antiviral-activity-and-mechanism-of-release
#1
Kyle E Giesler, Dennis C Liotta
The pharmacokinetic properties of tenofovir (TFV) and other charged nucleoside analogues are dramatically improved upon conjugation to a lipid prodrug. We previously prepared reduction-sensitive lipid conjugates of TFV that demonstrate superior antiviral activity compared to other lipid conjugates including the clinically approved formulation, tenofovir disoproxil fumarate (TDF). In continuation of that work, we have synthesized next-generation conjugates with reduced cytotoxicity that retain potent antiviral activity against HIV-1 and HBV with a therapeutic index >100000 for our most potent conjugate...
November 23, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27931518/vitamin-c-enhances-the-expression-of-il17-in-a-jmjd2-dependent-manner
#2
Mi Hye Song, Varun Sasidharan Nair, Kwon Ik Oh
Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in CD4+Foxp3+ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes...
December 9, 2016: BMB Reports
https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#3
Xiang Li, Xiaojing Yue, William A Pastor, Lizhu Lin, Romain Georges, Lukas Chavez, Sylvia M Evans, Anjana Rao
TET-family dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and oxidized methylcytosines in DNA. Here, we show that mouse embryonic stem cells (mESCs), either lacking Tet3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly skewed toward cardiac mesodermal fate. Conversely, ectopic expression of Tet3 enhanced neural differentiation and limited cardiac mesoderm specification. Genome-wide analyses showed that Tet3 mediates cell-fate decisions by inhibiting Wnt signaling, partly through promoter demethylation and transcriptional activation of the Wnt inhibitor secreted frizzled-related protein 4 (Sfrp4)...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27925498/behavior-of-tetracycline-and-sulfamethoxazole-and-their-corresponding-resistance-genes-in-three-dimensional-biofilm-electrode-reactors-with-low-current
#4
Shuai Zhang, Hai L Song, Xiao L Yang, Xi Z Long, Xi Liu, Tong Q Chen
Antibiotics and antibiotic resistance genes (ARGs) have become major health concerns. In this study, three-dimensional biofilm-electrode reactors (3D-BERs) under low current were designed to assess their performance in removing tetracycline (TC) and sulfamethoxazole (SMX) from synthetic wastewater. In addition, the fates of the corresponding ARGs in microbial communities were investigated. The mass removal ratios of TC and SMX by the 3D-BERs were 82.6-97.3% and 72.2-93.2%, respectively. There were obvious increases in the relative abundances of all target genes after ∼2 months...
December 7, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27925387/microcomputed-tomography-evaluation-of-volumetric-shrinkage-of-bulk-fill-composites-in-class-ii-cavities
#5
Hamad Algamaiah, Camila S Sampaio, Lindiane C Rigo, Malvin N Janal, Marcelo Giannini, Estevam A Bonfante, Paulo G Coelho, Andre F Reis, Ronaldo Hirata
PURPOSE: This study aimed to quantify polymerization shrinkage of one conventional and three bulk-fill composites, under bonded and unbonded conditions, in Class II preparations using 3D microcomputed tomography (μCT) and report its location. MATERIALS AND METHODS: Preparations (2.5 mm occlusal depth × 4 mm wide × 4 mm mesial box and 1 mm beyond the CEJ distal box depth) were made in 48 human extracted molars (n = 6). Four composites were tested, one regular (Vitalescence/VIT) and three bulk-fill: SureFil SDR Flow (SDR), Tetric EvoCeram Bulk Fill (TET), and Filtek flowable Bulk Fill (FIL)...
December 7, 2016: Journal of Esthetic and Restorative Dentistry
https://www.readbyqxmd.com/read/27925229/plga-ptmc-cultured-bone-mesenchymal-stem-cell-scaffold-enhances-cartilage-regeneration-in-tissue-engineered-tracheal-transplantation
#6
Bingyang Yan, Zhipei Zhang, Xiaoping Wang, Yunfeng Ni, Yongshi Liu, Tao Liu, Wuping Wang, Hao Xing, Ying Sun, Jian Wang, Xiao-Fei Li
The treatment of long-segment tracheal defect requires the transplantation of effective tracheal substitute, and the tissue-engineered trachea (TET) has been proposed as an ideal tracheal substitute. The major cause of the failure of segmental tracheal defect reconstruction by TET is airway collapse caused by the chondromalacia of TET cartilage. The key to maintain the TET structure is the regeneration of chondrocytes in cartilage, which can secrete plenty of cartilage matrices. To address the problem of the chondromalacia of TET cartilage, this study proposed an improved strategy...
December 7, 2016: Artificial Organs
https://www.readbyqxmd.com/read/27924045/a-novel-method-for-the-simultaneous-identification-of-methylcytosine-and-hydroxymethylcytosine-at-a-single-base-resolution
#7
Yuki Kawasaki, Yukiko Kuroda, Isao Suetake, Shoji Tajima, Fumitoshi Ishino, Takashi Kohda
Since the discovery of oxidative demethylation of methylcytosine (mC) by Tet enzymes, an analytical method has been urgently needed that would enable the identification of mC and hydroxymethylcytosine (hmC) at the single base resolution level, because their roles in gene regulation are quite different from each other. However, the bisulfite sequencing method, the gold standard for DNA methylation analysis at present, does not distinguish them. Recently reported alternative methods, such as oxBS-seq and TAB-seq, are not even capable of determining mC and hmC simultaneously...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923996/binding-of-mbd-proteins-to-dna-blocks-tet1-function-thereby-modulating-transcriptional-noise
#8
Anne K Ludwig, Peng Zhang, Florian D Hastert, Stephanie Meyer, Cathia Rausch, Henry D Herce, Udo Müller, Anne Lehmkuhl, Ines Hellmann, Carina Trummer, Christian Storm, Heinrich Leonhardt, M Cristina Cardoso
Aberrant DNA methylation is a hallmark of various human disorders, indicating that the spatial and temporal regulation of methylation readers and modifiers is imperative for development and differentiation. In particular, the cross-regulation between 5-methylcytosine binders (MBD) and modifiers (Tet) has not been investigated. Here, we show that binding of Mecp2 and Mbd2 to DNA protects 5-methylcytosine from Tet1-mediated oxidation. The mechanism is not based on competition for 5-methylcytosine binding but on Mecp2 and Mbd2 directly restricting Tet1 access to DNA...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923773/mitochondrial-protein-lipoylation-and-the-2-oxoglutarate-dehydrogenase-complex-controls-hif1%C3%AE-stability-in-aerobic-conditions
#9
Stephen P Burr, Ana S H Costa, Guinevere L Grice, Richard T Timms, Ian T Lobb, Peter Freisinger, Roger B Dodd, Gordon Dougan, Paul J Lehner, Christian Frezza, James A Nathan
Hypoxia-inducible transcription factors (HIFs) control adaptation to low oxygen environments by activating genes involved in metabolism, angiogenesis, and redox homeostasis. The finding that HIFs are also regulated by small molecule metabolites highlights the need to understand the complexity of their cellular regulation. Here we use a forward genetic screen in near-haploid human cells to identify genes that stabilize HIFs under aerobic conditions. We identify two mitochondrial genes, oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which when mutated stabilize HIF1α in a non-hydroxylated form...
November 8, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27919426/diagnostic-accuracy-of-treadmill-exercise-tests-among-chinese-women-with-coronary-artery-diseases-a-systematic-review-and-meta-analysis
#10
REVIEW
Yi Sun, Wei Li, Lu Yin, Limei Wei, Yang Wang
BACKGROUND: The treadmill exercise test (TET) is one of the most common noninvasive diagnosis approaches for ischemic heart diseases, but potential reduction of TET accuracy among Chinese female patients was ignored by most studies, especially in perimenopause women. Hence, we aim to perform a systematic review and meta-analysis evaluating the TET diagnostic accuracy for Chinese women compared with coronary angiography (CAG). METHODS: PubMed, MEDLINE, EMBASE, CNKI and WANFANG (1990 to 2015) were performed to identify studies assessing the diagnostic accuracy of TET versus CAG...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27918559/mutations-along-a-tet2-active-site-scaffold-stall-oxidation-at-5-hydroxymethylcytosine
#11
Monica Yun Liu, Hedieh Torabifard, Daniel J Crawford, Jamie E DeNizio, Xing-Jun Cao, Benjamin A Garcia, G Andrés Cisneros, Rahul M Kohli
Ten-eleven translocation (TET) enzymes catalyze stepwise oxidation of 5-methylcytosine (mC) to yield 5-hydroxymethylcytosine (hmC) and the rarer bases 5-formylcytosine (fC) and 5-carboxylcytosine (caC). Stepwise oxidation obscures how each individual base forms and functions in epigenetic regulation, and prompts the question of whether TET enzymes primarily serve to generate hmC or are adapted to produce fC and caC as well. By mutating a single, conserved active site residue in human TET2, Thr1372, we uncovered enzyme variants that permit oxidation to hmC but largely eliminate fC and caC...
December 5, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#12
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27916660/isoform-switch-of-tet1-regulates-dna-demethylation-and-mouse-development
#13
Wenhao Zhang, Weikun Xia, Qiujun Wang, Aaron J Towers, Jiayu Chen, Rui Gao, Yu Zhang, Chia-An Yen, Ah Young Lee, Yuanyuan Li, Chen Zhou, Kaili Liu, Jing Zhang, Tian-Peng Gu, Xiuqi Chen, Zai Chang, Danny Leung, Shaorong Gao, Yong-Hui Jiang, Wei Xie
The methylcytosine oxidase TET proteins play important roles in DNA demethylation and development. However, it remains elusive how exactly they target substrates and execute oxidation. Interestingly, we found that, in mice, the full-length TET1 isoform (TET1e) is restricted to early embryos, embryonic stem cells (ESCs), and primordial germ cells (PGCs). By contrast, a short isoform (TET1s) is preferentially expressed in somatic cells, which lacks the N terminus including the CXXC domain, a DNA-binding module that often recognizes CpG islands (CGIs) where TET1 predominantly occupies...
November 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27916605/modulation-of-drug-resistance-and-biofilm-formation-of-staphylococcus-aureus-isolated-from-the-oral-cavity-of-tunisian-children
#14
Tarek Zmantar, Rihab Ben Slama, Kais Fdhila, Bochra Kouidhi, Amina Bakhrouf, Kamel Chaieb
OBJECTIVES: This study aims to investigate the antimicrobial and the anti-biofilm activities of Lactobacillus plantarum extract (LPE) against a panel of oral Staphylococcus aureus (n=9) and S. aureus ATCC 25923. The in vitro ability of LPE to modulate bacterial resistance to tetracycline, benzalchonium chloride (BC), and chlorhexidine (CHX) were tested also. METHODS: The MICs and MBCs of LPE, tetracycline (TET), CHX and BC were determined in absence and in presence of a sub-MIC doses of LPE (1/2 MIC)...
December 1, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27915294/insightful-directed-evolution-of-escherichia-coli-quorum-sensing-promoter-region-of-the-lsracdbfg-operon-a-tool-for-synthetic-biology-systems-and-protein-expression
#15
Pricila Hauk, Kristina Stephens, Ryan Mckay, Chelsea Ryan Virgile, Hana Ueda, Marc Ostermeier, Kyoung-Seok Ryu, Herman O Sintim, William E Bentley
Quorum sensing (QS) regulates many natural phenotypes (e.q. virulence, biofilm formation, antibiotic resistance), and its components, when incorporated into synthetic genetic circuits, enable user-directed phenotypes. We created a library of Escherichia coli lsr operon promoters using error-prone PCR (ePCR) and selected for promoters that provided E. coli with higher tetracycline resistance over the native promoter when placed upstream of the tet(C) gene. Among the fourteen clones identified, we found several mutations in the binding sites of QS repressor, LsrR...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911867/decreased-5-hydroxymethylcytosine-levels-correlate-with-cancer-progression-and-poor-survival-a-systematic-review-and-meta-analysis
#16
Zhaoli Chen, Xuejiao Shi, Lanwei Guo, Yuan Li, Mei Luo, Jie He
Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and then to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), resulting in genomic DNA demethylation. Decreased 5-hmC levels have been reported in a variety of cancers, and loss of 5-hmC might be considered an epigenetic hallmark of cancer. However, the prognostic value of decreased 5-hmC in cancers remain controversial. Here, a systematic review was performed by conducting an electronic search of PubMed, EMBASE, Web of Science and the Cochrane Library...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909720/tetrandrine-inhibits-glioma-stem-like-cells-by-repressing-%C3%AE-catenin-expression
#17
Yong Zhang, Yu-Lin Wen, Ji-Wei Ma, Jie-Cheng Ye, Xiao Wang, Jian-Xian Huang, Chao-Yue Meng, Xiao-Ze Xu, Shao-Xiang Wang, Xue-Yun Zhong
Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27908198/tet-proteins-master-regulators-of-vertebrate-body-plan-formation
#18
Ozren Bogdanović
No abstract text is available yet for this article.
December 2, 2016: Epigenomics
https://www.readbyqxmd.com/read/27905578/2-r-fluorinated-mc-hmc-fc-and-cac-triphosphates-are-substrates-for-dna-polymerases-and-tet-enzymes
#19
A S Schröder, E Parsa, K Iwan, F R Traube, M Wallner, S Serdjukow, T Carell
A deeper investigation of the chemistry that occurs on the newly discovered epigenetic DNA bases 5-hydroxymethyl-(hmdC), 5-formyl-(fdC), and 5-carboxy-deoxycytidine (cadC) requires chemical tool compounds, which are able to dissect the different potential reaction pathways in cells. Here we report that the 2'-(R)-fluorinated derivatives F-hmdC, F-fdC, and F-cadC, which are resistant to removal by base excision repair, are good substrates for DNA polymerases and TET enzymes. This result shows that the fluorinated compounds are ideal tool substances to investigate potential C-C-bond cleaving reactions in the context of active demethylation...
December 1, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27903986/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#20
Ambroise Marçais, Laetitia Waast, Julie Bruneau, Katia Hanssens, Vahid Asnafi, Philippe Gaulard, Felipe Suarez, Patrice Dubreuil, Antoine Gessain, Olivier Hermine, Claudine Pique
Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells...
November 26, 2016: Oncotarget
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