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https://www.readbyqxmd.com/read/28538185/regulation-of-active-dna-demethylation-through-rar-mediated-recruitment-of-a-tet-tdg-complex
#1
Haider M Hassan, Bart Kolendowski, Majdina Isovic, Kerstin Bose, Helen J Dranse, Arthur V Sampaio, T Michael Underhill, Joseph Torchia
Retinoic acid (RA) plays important roles in development, growth, and homeostasis through regulation of the nuclear receptors for RA (RARs). Herein, we identify Hypermethylated in Cancer 1 (Hic1) as an RA-inducible gene. HIC1 encodes a tumor suppressor, which is often silenced by promoter hypermethylation in cancer. Treatment of cells with an RAR agonist causes a rapid recruitment of an RAR/RXR complex consisting of TDG, the lysine acetyltransferase CBP, and TET 1/2 to the Hic1 promoter. Complex binding coincides with a transient accumulation of 5fC/5caC and concomitant upregulation of Hic1 expression, both of which are TDG dependent...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28533366/mechanism-of-h2s-mediated-protection-against-oxidative-stress-in-escherichia-coli
#2
Alexander Mironov, Tatyana Seregina, Maxim Nagornykh, Lyly G Luhachack, Natalya Korolkova, Liubov Errais Lopes, Vera Kotova, Gennady Zavilgelsky, Rustem Shakulov, Konstantin Shatalin, Evgeny Nudler
Endogenous hydrogen sulfide (H2S) renders bacteria highly resistant to oxidative stress, but its mechanism remains poorly understood. Here, we report that 3-mercaptopyruvate sulfurtransferase (3MST) is the major source of endogenous H2S in Escherichia coli Cellular resistance to H2O2 strongly depends on the activity of mstA, a gene that encodes 3MST. Deletion of the ferric uptake regulator (Fur) renders ∆mstA cells hypersensitive to H2O2 Conversely, induction of chromosomal mstA from a strong pLtetO-1 promoter (P tet -mstA) renders ∆fur cells fully resistant to H2O2 Furthermore, the endogenous level of H2S is reduced in ∆fur or ∆sodA ∆sodB cells but restored after the addition of an iron chelator dipyridyl...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533243/roles-of-ramr-and-tet-a-mutations-in-conferring-tigecycline-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-clinical-isolates
#3
Sheng-Kang Chiu, Li-Yueh Huang, Hsi Chen, Yu-Kuo Tsai, Ci-Hong Liou, Jung-Chung Lin, L Kristopher Siu, Feng-Yee Chang, Kuo-Ming Yeh
Tigecycline is regarded as a last-resort treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, but increasing numbers of tigecycline-resistant K. pneumoniae isolates have been reported. Tigecycline resistance mechanisms are underdetermined in CRKP. This study aimed to elucidate mechanisms underlying tigecycline resistance in 16 tigecycline- and carbapenem-resistant K. pneumoniae (TCRKP) isolates. Mutations in tigecycline resistance determinant genes (ramR, acrR, oqxR, tet(A), tet(L), tet(X), tet(M), rpsJ) were assessed by PCR amplicon sequencing, and mutations in ramR and tet(A) exhibited high prevalences individually (81%) and in combination (63%)...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#4
Wei Qiu, Ai-Li Zhang, Ye Tian
Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#5
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28521490/transcript-levels-of-ten-eleven-translocation-type-1-3-in-cervical-cancer-and-non-cancerous-cervical-tissues
#6
Dorota Ewa Bronowicka-Kłys, Andrzej Roszak, Piotr Pawlik, Stefan Sajdak, Anna Sowińska, Paweł Piotr Jagodziński
Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521175/prognostic-significance-of-tet2-mutations-in-myelodysplastic-syndromes-a-meta-analysis
#7
Zhen Guo, Shao-Kai Zhang, Zhe Zou, Rui-Hua Fan, Xiao-Dong Lyu
Tet methylcytosine dioxygenase 2 (TET2) mutations occur frequently in myelodysplastic syndromes (MDS), but its prognostic impact has not been fully assessed and was controversial. Therefore, we performed a meta-analysis to evaluate the prognostic significance of TET2 mutations in MDS. PubMed, EMBASE databases and Cochrane Library were searched for studies reporting TET2 mutations and overall survival in MDS. Hazard ratios (HR) with 95% confidence interval (CI) were determined using random-effect modeling. A total of 1494 patients from nine studies were subjected to meta-analysis...
March 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28516210/antibiotic-resistance-genes-in-surface-water-of-eutrophic-urban-lakes-are-related-to-heavy-metals-antibiotics-lake-morphology-and-anthropic-impact
#8
Yuyi Yang, Chen Xu, Xinhua Cao, Hui Lin, Jun Wang
Urban lakes are impacted by heavy human activities and represent potential reservoirs for antibiotic resistance genes. In this study, six urban lakes in Wuhan, central China were selected to analyze the distribution of sulfonamide resistance (sul) genes, tetracycline resistance (tet) genes and quinolone resistance (qnr) genes and their relationship with heavy metals, antibiotics, lake morphology and anthropic impact. sul1 and sul2 were detected in all six lakes and dominated the types of antibiotic resistance genes, which accounted for 86...
May 17, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28514756/elevated-crp-levels-predict-poor-outcome-and-tumor-recurrence-in-patients-with-thymic-epithelial-tumors-a-pro-and-retrospective-analysis
#9
Stefan Janik, Christine Bekos, Philipp Hacker, Thomas Raunegger, Bahil Ghanim, Elisa Einwallner, Lucian Beer, Walter Klepetko, Leonhard Müllauer, Hendrik J Ankersmit, Bernhard Moser
OBJECTIVE: Scarce information exists on the pathogenesis of thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed to investigate the clinical relevance of CRP in patients with TETs. RESULTS: Pretreatment CRP serum concentrations were significantly elevated in patients with TETs, particularly TCs and metastatic TETs. After complete tumor resection CRP serum concentrations were decreased (p = 0...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514526/direct-medial-approach-in-surgical-fixation-of-fractures-in-the-posterior-aspect-of-the-medial-malleolus
#10
Ang Chay-You, Ling Marcus, Koh Joyce Suang-Bee, Howe Tet-Sen
BACKGROUND: Fractures in the posterior aspect of the medial malleolus form an important subset of ankle fractures and the indications for fixation include involvement of > 25% of the articular surface or an articular step off by > 2mm. Several approaches have been described but there has been no recent study on the direct medial approach. METHODS: Five fresh frozen cadaveric ankles were dissected using the direct medial approach. A longitudinal incision of 10cm was centered directly over the medial malleolus and deepened straight down to the bone...
May 17, 2017: Clinical Anatomy
https://www.readbyqxmd.com/read/28513551/the-regulatory-capacity-of-bivalent-genes-a-theoretical-approach
#11
Torsten Thalheim, Maria Herberg, Markus Loeffler, Joerg Galle
Bivalent genes are frequently associated with developmental and lineage specification processes. Resolving their bivalency enables fast changes in their expression, which potentially can trigger cell fate decisions. Here, we provide a theoretical model of bivalency that allows for predictions on the occurrence, stability and regulatory capacity of this prominent modification state. We suggest that bivalency enables balanced gene expression heterogeneity that constitutes a prerequisite of robust lineage priming in somatic stem cells...
May 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28513140/hybrid-prodrug-nanoparticles-with-tumor-penetration-and-programmed-drug-activation-for-enhanced-chemo-resistant-cancer-therapy
#12
Caiyan Zhao, Leihou Shao, Jianqing Lu, Xiongwei Deng, Yujia Tong, Yan Wu
Despite nanomedicine has shown great potential for reverse cancer cells resistance, the suboptimal transport across multiple biological obstacles seriously impedes its reaching targets at an efficacious level, which remains the challenging hurdle for clinical success in resistant cancer therapy. Here, a lipid-based hybrid nanoparticle was designed to efficiently deliver the therapeutics to resistant cells and treat resistant cancer in vivo. The hybrid nanoparticles (D-NPs/TET) are composed of a pH-responsive prodrug 1,2-distearoyl-snglycero-3-phosphoethanolamine (DSPE)-doxorubicin (DOX), a efflux inhibitor tetrandrine (TET) and a surfactant 1,2-distearoyl-snglycero-3-phosphoethanolamine-[methoxy (polyethylene glycol)-2000] (DSPE-mPEG2000), which hierarchically combatted the sequential physiological and pathological barriers of drug resistance, exhibited prolonged blood circulation, high tumor accumulation, and deep tumor parenchyma penetration...
May 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28510333/tetracycline-inducible-and-reversible-stable-gene-expression-in-human-ipsc-derived-neural-progenitors-and-in-the-postnatal-mouse-brain
#13
Aslam Abbasi Akhtar, Joshua J Breunig
The pB-tet-GOI plasmid system allows for stable piggyBac transposition-mediated integration into cells, a fluorescent nuclear reporter to identify cells that have been transfected, and robust transgene activation or suppression upon the addition of dox to the cell culture or diet of the animal. Furthermore, the addition of luciferase downstream of the target gene allows for quantitative assessment of gene activity in a non-invasive manner. The protocols herein provide instructions for the use of this system in cell lines and in the neonatal mouse brain...
May 16, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28504889/genetic-characterization-of-vana-enterococcus-faecium-isolates-from-wild-red-legged-partridges-in-portugal
#14
Vanessa Silva, Gilberto Igrejas, Isabel Carvalho, Fernando Peixoto, Lucas Cardoso, José Eduardo Pereira, Rosa Del Campo, Patricia Poeta
Vancomycin-resistant enterococci (VRE) have been detected in wild animals representing a public health concern. The red-legged partridge (Alectoris rufa) is a common game bird and its meat is consumed in several countries, including Portugal. Three hundred five fecal samples of red-legged partridge from the north of Portugal were screened for VRE. Samples were cultured on Slanetz-Bartley agar supplemented with vancomycin (4 mg/L) and six vanA-Enterococcus faecium were recovered. Isolates were tested for antibiotic resistance and virulence genes...
May 15, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28504700/lineage-specific-functions-of-tet1-in-the-postimplantation-mouse-embryo
#15
Rita Khoueiry, Abhishek Sohni, Bernard Thienpont, Xinlong Luo, Joris Vande Velde, Michela Bartoccetti, Bram Boeckx, An Zwijsen, Anjana Rao, Diether Lambrechts, Kian Peng Koh
The mammalian TET enzymes catalyze DNA demethylation. While they have been intensely studied as major epigenetic regulators, little is known about their physiological roles and the extent of functional redundancy following embryo implantation. Here we define non-redundant roles for TET1 at an early postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are not detectably expressed. TET1 regulates numerous genes defining differentiation programs in the epiblast and extraembryonic ectoderm...
May 15, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28501652/a-new-adenovector-system-for-implementing-thymulin-gene-therapy-for-inflammatory-disorders
#16
María F Zappa-Villar, Micaela López-León, Joaquín Pardo, Mariana Costa, Rosana Crespo, Mireille Dardenne, Rodolfo G Goya, Paula C Reggiani
Thymulin is a thymic peptide possessing anti-inflammatory effects. In order to manipulate thymulin expression in gene therapy studies, we built a bidirectional regulatable two-vector Tet-Off system and the corresponding control system. The experimental two-vector system, ETV, consists of a recombinant adenovector (RAd) harboring an expression cassette centered on a Tet-Off bidirectional promoter flanked by a synthetic gene for thymulin and the gene for humanized Green Fluorescent Protein (hGFP). The second adenovector of this system, RAd-tTA, constitutively expresses the regulatory protein tTA...
May 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28493125/conditional-knockdown-of-endogenous-micrornas-in-cho-cells-using-tet-on-sandi-sponge-vectors
#17
Alan Costello, Nga Lao, Martin Clynes, Niall Barron
MicroRNAs (miRNAs) are small, noncoding RNAs of about 22 nucleotides in length and have proven to be useful targets for genetic modifications for desirable phenotype in the biotech industry. The use of constitutively expressed "miRNA sponge" vectors in which multiple, tandem miRNA binding sites containing transcripts are transcriptionally regulated by a constitutive promoter for down regulating the levels of endogenous microRNAs in Chinese hamster ovary (CHO) cells has shown to be more advantageous than using synthetic antisense oligonucleotides...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28490739/honokiol-inhibits-ultraviolet-radiation-induced-immunosuppression-through-inhibition-of-ultraviolet-induced-inflammation-and-dna-hypermethylation-in-mouse-skin
#18
Ram Prasad, Tripti Singh, Santosh K Katiyar
Ultraviolet (UV) radiation exposure induces immunosuppression, which contributes to the development of cutaneous malignancies. We investigated the effects of honokiol, a phytochemical found in plants of the genus Magnolia, on UVB-induced immunosuppression using contact hypersensitivity (CHS) as a model in C3H/HeN mice. Topical application of honokiol (0.5 and 1.0 mg/cm(2) skin area) had a significant preventive effect on UVB-induced suppression of the CHS response. The inflammatory mediators, COX-2 and PGE2, played a key role in this effect, as indicated by honokiol inhibition of cyclooxygenase-2 (COX-2) expression and PGE2 production in the UVB-exposed skin...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28486946/thymic-epithelial-tumors-phenotype-relies-on-mir-145-5p-epigenetic-regulation
#19
Teresa Bellissimo, Federica Ganci, Enzo Gallo, Andrea Sacconi, Claudia Tito, Luciana De Angelis, Claudio Pulito, Silvia Masciarelli, Daniele Diso, Marco Anile, Vincenzo Petrozza, Felice Giangaspero, Edoardo Pescarmona, Francesco Facciolo, Federico Venuta, Mirella Marino, Giovanni Blandino, Francesco Fazi
BACKGROUND: Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p...
May 10, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28484230/an-all-in-one-tet-on-3g-inducible-piggybac-system-for-human-pluripotent-stem-cells-and-derivatives
#20
Lauren N Randolph, Xiaoping Bao, Chikai Zhou, Xiaojun Lian
Human pluripotent stem cells (hPSCs) offer tremendous promise in tissue engineering and cell-based therapies due to their unique combination of two properties: pluripotency and unlimited proliferative capacity. However, directed differentiation of hPSCs to clinically relevant cell lineages is needed to achieve the goal of hPSC-based therapies. This requires a deep understanding of how cell signaling pathways converge on the nucleus to control differentiation and the ability to dissect gene function in a temporal manner...
May 8, 2017: Scientific Reports
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