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single cell methylation

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https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#1
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720530/downregulation-of-protein-phosphatase-2a-by-apolipoprotein-e-implications-for-alzheimer-s-disease
#2
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
July 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28716738/photodynamic-therapy-and-pain-a-systematic-review
#3
Jennifer Maria Ang, Irbaz Bin Riaz, Muhammad Umar Kamal, Gyorgy Paragh, Nathalie C Zeitouni
Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization. Procedure-associated pain limits widespread PDT use and by early termination of treatment can decrease overall therapeutic efficacy. Here we review and assess reported interventions on PDT-associated pain, in order to identify the most promising methods to manage treatment-associated pain and identify focus for future studies. Literature search was performed using MEDLINE, EMBASE, and the Cochrane Library by two independent reviewers to select publications that assessed and compared pain quantitatively during PDT treatment for actinic keratoses, basal cell carcinomas, and/or in situ squamous cell carcinomas...
July 14, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28709138/multimodal-nonlinear-microscope-based-on-a-compact-fiber-format-laser-source
#4
Francesco Crisafi, Vikas Kumar, Antonio Perri, Marco Marangoni, Giulio Cerullo, Dario Polli
We present a multimodal non-linear optical (NLO) laser-scanning microscope, based on a compact fiber-format excitation laser and integrating coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS) and two-photon-excitation fluorescence (TPEF) on a single platform. We demonstrate its capabilities in simultaneously acquiring CARS and SRS images of a blend of 6-μm poly(methyl methacrylate) beads and 3-μm polystyrene beads. We then apply it to visualize cell walls and chloroplast of an unprocessed fresh leaf of Elodea aquatic plant via SRS and TPEF modalities, respectively...
July 5, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28700344/decoy-receptor-1-dcr1-promoter-hypermethylation-and-response-to-irinotecan-in-metastatic-colorectal-cancer
#5
Linda J W Bosch, Geert Trooskens, Petur Snaebjornsson, Veerle M H Coupé, Sandra Mongera, Josien C Haan, Susan D Richman, Miriam Koopman, Jolien Tol, Tim de Meyer, Joost Louwagie, Luc Dehaspe, Nicole C T van Grieken, Bauke Ylstra, Henk M W Verheul, Manon van Engeland, Iris D Nagtegaal, James G Herman, Philip Quirke, Matthew T Seymour, Cornelis J A Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A Meijer
Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients.Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI))...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693997/lectin-from-canavalia-villosa-seeds-a-glucose-mannose-specific-protein-and-a-new-tool-for-inflammation-studies
#6
Claudia F Lossio, Cleane G Moreira, Renata M F Amorim, Clareane S Nobre, Mayara T L Silva, Cornevile C Neto, Vanir R Pinto-Junior, Ivanice B Silva, Julia Campos, Ana Maria S Assreuy, Benildo S Cavada, Kyria S Nascimento
With important carbohydrate binding properties, lectins are proteins able to decipher the glycocode, and as such, they can be used in bioassays involving cell-cell communication, protein targeting, inflammation, and hypernociception, among others. In this study, a new glucose/mannose-specific lectin from Canavalia villosa seeds (Cvill) was isolated by a single affinity chromatography step in a Sephadex(®) G-50 column, with a purification yield of 19.35mg of lectin per gram of powdered seed. Analysis of intact protein by mass spectrometry showed the lectin is composed of three polypeptide chains, including a 25...
July 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28693405/genetics-and-immunodysfunction-underlying-beh%C3%A3-et-s-disease-and-immunomodulant-treatment-approaches
#7
Arash Salmaninejad, Arezoo Gowhari, Seyedmojtaba Hosseini, Saeed Aslani, Meysam Yousefi, Tayyeb Bahrami, Masoume Ebrahimi, Abolfazl Nesaei, Masoud Zal
Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28689409/global-phosphoproteomic-analysis-of-insulin-akt-mtorc1-s6k-signaling-in-rat-hepatocytes
#8
Yuanyuan Zhang, Yajie Zhang, Yonghao Yu
Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic and physiological factors interact to cause insulin resistance, deregulated signaling by phosphorylation is a common underlying mechanism. In particular, the specific phosphorylation-dependent regulatory mechanisms and signaling outputs of insulin are poorly understood in hepatocytes, which represents one of the most important insulin-responsive cell types. Using primary rat hepatocytes as a model system, we performed reductive dimethylation (ReDi)-based quantitative mass spectrometric analysis and characterized the phosphoproteome that is regulated by insulin as well as its key downstream kinases including Akt, mTORC1, and S6K...
July 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28684555/statistically-robust-methylation-calling-for-whole-transcriptome-bisulfite-sequencing-reveals-distinct-methylation-patterns-for-mouse-rnas
#9
Carine Legrand, Francesca Tuorto, Mark Hartmann, Reinhard Liebers, Dominik Jacob, Mark Helm, Frank Lyko
(Cytosine-5) RNA methylation plays an important role in several biologically and pathologically relevant processes. However, owing to methodological limitations, the transcriptome-wide distribution of this mark has remained largely unknown. We previously established RNA bisulfite sequencing as a method for the analysis of RNA (cytosine-5) methylation patterns at single-base resolution. More recently, next-generation sequencing has provided opportunities to establish transcriptome-wide maps of this modification...
July 6, 2017: Genome Research
https://www.readbyqxmd.com/read/28682229/-epigenetic-mechanisms-and-alcohol-use-disorders-a-potential-therapeutic-target
#10
Rémi Legastelois, Jérôme Jeanblanc, Catherine Vilpoux, Erika Bourguet, Mickael Naassila
Alcohol use disorder is a devastating illness with a profound health impact, and its development is dependent on both genetic and environmental factors. This disease occurs over time and requires changes in brain gene expression. There is converging evidence suggesting that the epigenetic processes may play a role in the alcohol-induced gene regulations and behavior such as the intervention of DNA methylation and histone acetylation. Histone acetylation, like histone methylation, is a highly dynamic process regulated by two classes of enzymes: histone acetyltransferases and histone deacetylases (HDACs)...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28677607/design-synthesis-crystal-structure-and-in-vitro-cytotoxic-properties-of-a-novel-schiff-base-derived-from-indole-and-biphenyl
#11
Fan Zhi Bu, Xue Jie Tan, Dian Xiang Xing, Chao Wang
A novel and potentially active dihydroorotate dehydrogenase (DHODH) inhibitor, namely 3-({(E)-[(E)-1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1H-indole (BEHI) acetonitrile disolvate, C23H19N3·2CH3CN, has been designed and synthesized. The structure of BEHI was characterized by elemental analysis, Q-TOF (quadrupole time-of-flight) MS, NMR, UV-Vis and single-crystal X-ray diffraction. The antitumour activity of the target molecule was evaluated by the MTT method. Results indicated that BEHI exhibited rather potent cytotoxic activity against human A549 (IC50 = 20...
July 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/28676804/simultaneous-downregulation-of-mthfr-and-comt-in-switchgrass-affects-plant-performance-and-induces-lesion-mimic-cell-death
#12
Sijia Liu, Chunxiang Fu, Jiqing Gou, Liang Sun, David Huhman, Yunwei Zhang, Zeng-Yu Wang
Switchgrass (Panicum virgatum) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O-methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT-deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28674382/the-destiny-of-the-resistance-susceptibility-against-gcrv-is-controlled-by-epigenetic-mechanisms-in-cik-cells
#13
Xueying Shang, Chunrong Yang, Quanyuan Wan, Youliang Rao, Jianguo Su
Hemorrhagic disease caused by grass carp reovirus (GCRV) has severely threatened the grass carp (Ctenopharyngodon idella) cultivation industry. It is noteworthy that the resistance against GCRV infection was reported to be inheritable, and identified at both individual and cellular levels. Therefore, this work was inspired and dedicated to unravel the molecular mechanisms of fate decision post GCRV infection in related immune cells. Foremost, the resistant and susceptible CIK (C. idella kidney) monoclonal cells were established by single cell sorting, subculturing and infection screening successively...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674263/pharmacological-profiles-of-a-highly-potent-and-long-acting-angiotensin-ii-receptor-antagonist-fimasartan-in-rats-and-dogs-after-oral-administration
#14
Soo Heui Paik, Yong Ha Chi, Joo Han Lee, Hee-Soo Han, Kyung-Tae Lee
The pharmacological profile of fimasartan, [2-n-butyl-5-dimethylamino-thiocarbonyl-methyl-6-methyl-3-{[2-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-pyrimidin-4(3H)-one, a new non-peptide angiotensin type 1 (AT1)-selective angiotensin receptor antagonist, has been investigated in a variety of in vitro and in vivo experimental models. In the present study, fimasartan showed slow dissociation and irreversible binding to AT1 subtype receptors in membrane fractions of HEK-293 cells with a Kd of 0.03 nM and a T1/2 of 63...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28674067/genome-scale-mutational-analysis-of-geobacter-sulfurreducens-reveals-distinct-molecular-mechanisms-for-respiration-and-sensing-of-poised-electrodes-vs-fe-iii-oxides
#15
Chi Ho Chan, Caleb E Levar, Fernanda Jiménez-Otero, Daniel R Bond
Geobacter sulfurreducens generates electrical current by coupling intracellular oxidation of organic acids to reduction of proteins on the cell surface that are able to interface with electrodes. This ability is attributed to the bacterium's capacity to respire other extracellular electron acceptors that require contact, such as insoluble metal oxides. To directly investigate the genetic basis of electrode-based respiration, we constructed Geobacter sulfurreducens transposon-insertion sequencing (Tn-Seq) libraries for growth with soluble fumarate or an electrode as the electron acceptor...
July 3, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28667872/polysubstituted-2-aminoimidazoles-as-anti-biofilm-and-antiproliferative-agents-discovery-of-potent-lead
#16
Rupinder Kaur Gill, Virender Kumar, Stijn C A Robijns, Hans P L Steenackers, Erik V Van der Eycken, Jitender Bariwal
Most of the human bacterial infections are associated with the biofilm formation and the natural tolerance of biofilms to antibiotics challenges treatment. Because of their low immunity, cancer patients are especially susceptible to bacterial infections. Compounds with anti-biofilm activity could therefore become a useful adjunct to chemotherapy, in particular if they also show antiproliferative activities. Taking this into consideration and as a result of our continuous interest in 2-aminoimidazole derivatives, we have designed and synthesized a series of novel polysubstituted 2-aminoimidazoles (20a-x)...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28666936/human-induced-pluripotent-stem-cell-hipsc-derived-neurons-respond-to-convulsant-drugs-when-co-cultured-with-hipsc-derived-astrocytes
#17
Misawa Niki Ishii, Koji Yamamoto, Masanobu Shoji, Asano Asami, Yuji Kawamata
Accurate risk assessment for drug-induced seizure is expected to be performed before entering clinical studies because of its severity and fatal damage to drug development. Induced pluripotent stem cell (iPSC) technology has allowed the use of human neurons and glial cells in toxicology studies. Recently, several studies showed the advantage of co-culture system of human iPSC (hiPSC)-derived neurons with rodent/human primary astrocytes regarding neuronal functions. However, the application of hiPSC-derived neurons for seizure risk assessment has not yet been fully addressed, and not at all when co-cultured with hiPSC-derived astrocytes...
June 27, 2017: Toxicology
https://www.readbyqxmd.com/read/28665997/independent-regulation-of-gene-expression-level-and-noise-by-histone-modifications
#18
Shaohuan Wu, Ke Li, Yingshu Li, Tong Zhao, Ting Li, Yu-Fei Yang, Wenfeng Qian
The inherent stochasticity generates substantial gene expression variation among isogenic cells under identical conditions, which is frequently referred to as gene expression noise or cell-to-cell expression variability. Similar to (average) expression level, expression noise is also subject to natural selection. Yet it has been observed that noise is negatively correlated with expression level, which manifests as a potential constraint for simultaneous optimization of both. Here, we studied expression noise in human embryonic cells with computational analysis on single-cell RNA-seq data and in yeast with flow cytometry experiments...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28661661/caulobacter-crescentus-cell-cycle-regulated-dna-methyltransferase-uses-a-novel-mechanism-for-substrate-recognition
#19
Clayton B Woodcock, Aziz B Yakubov, Norbert O Reich
Caulobacter crescentus relies on DNA methylation by the cell cycle-regulated methyltransferase (CcrM) in addition to key transcription factors to control the cell cycle and direct cellular differentiation. CcrM is shown here to efficiently methylate its cognate recognition site 5'-GANTC-3' in single-stranded and hemimethylated double-stranded DNA. We report the Km, kcat, kmethylation, and Kd for single-stranded and hemimethylated substrates, revealing discrimination of 10(7)-fold for noncognate sequences. The enzyme also shows a similar discrimination against single-stranded RNA...
July 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28661138/three-dimensional-scaffold-chip-with-thermosensitive-coating-for-capture-and-reversible-release-of-individual-and-cluster-of-circulating-tumor-cells
#20
Shi-Bo Cheng, Min Xie, Yan Chen, Jun Xiong, Ya Liu, Zhen Chen, Shan Guo, Ying Shu, Ming Wang, Bifeng Yuan, Wei-Guo Dong, Wei-Hua Huang
Tumor metastasis is attributed to circulating tumor cells (CTC) or CTC clusters. Many strategies have hitherto been designed to isolate CTCs, but there are few methods that can capture and gently release CTC clusters as efficient as single CTCs. Herein, we developed a three-dimensional (3D) scaffold chip with thermosensitive coating for high-efficiency capture and release of individual and cluster of CTCs. The 3D scaffold chip successfully combines the specific recognition and physically obstructed effect of 3D scaffold structure to significantly improve cell clusters capture efficiency...
June 29, 2017: Analytical Chemistry
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