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https://www.readbyqxmd.com/read/29434723/screening-for-key-genes-and-transcription-factors-in-ankylosing-spondylitis-by-rna-seq
#1
Zhongyang Xu, Xiuyu Wang, Yanping Zheng
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis and autoimmune disease, the etiology and pathogenesis of which remain largely unknown. In the present study, blood samples were harvested from patients with AS and from healthy volunteers as a normal control (NC) for RNA-sequencing. Differentially expressed genes (DEGs) in the AS group compared with the NC group were identified, and gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29343446/s-adenosyl-methionine-prevents-asd-like-behaviors-triggered-by-early-postnatal-valproic-acid-exposure-in-very-young-mice
#2
Asher Ornoy, Liza Weinstein-Fudim, Matanel Tfilin, Zivanit Ergaz, Joseph Yanai, Moshe Szyf, Gadi Turgeman
INTRODUCTION: A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. METHODS: ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight...
January 14, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29340929/s-adenosyl-methionine-and-transmethylation-pathways-in-neuropsychiatric-diseases-throughout-life
#3
Jin Gao, Catherine M Cahill, Xudong Huang, Joshua L Roffman, Stefania Lamon-Fava, Maurizio Fava, David Mischoulon, Jack T Rogers
S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways...
January 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29340097/s-adenosyl-methionine-sam-alters-the-transcriptome-and-methylome-and-specifically-blocks-growth-and-invasiveness-of-liver-cancer-cells
#4
Yan Wang, ZhongSheng Sun, Moshe Szyf
S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241413/novel-missense-mutations-in-gidb-gene-associated-with-streptomycin-resistance-in-mycobacterium-tuberculosis-insights-from-molecular-dynamics
#5
Bharati Pandey, Sonam Grover, Sukriti Goyal, Salma Jamal, Aditi Singh, Jagdeep Kaur, Abhinav Grover
Streptomycin was the first antibiotic used for the treatment of tuberculosis by inhibiting translational proof reading. Point mutation in gidB gene encoding S-adenosyl methionine (SAM)-dependent 7-methylguanosine (m7G) methyltransferase required for methylation of 16S rRNA confers streptomycin (STR) resistance. As there was no structural substantiation experimentally, gidB protein model was built by threading algorithm. In this work, molecular dynamics (MD) simulations coupled with binding free energy calculations were performed to outline the mechanism underlying high-level streptomycin resistance associated with three novel missense mutants including S70R, T146M and R187M...
December 14, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29232372/attenuated-expression-of-mtr-in-both-prenatally-androgenized-mice-and-women-with-the-hyperandrogenic-phenotype-of-pcos
#6
Lei Lei, Lijun Ding, Jing Su, Mengyuan Liu, Qingqing Shi, Jianjun Zhou, Haixiang Sun, Guijun Yan
Polycystic ovary syndrome (PCOS) is a common endocrine, metabolic and heterogeneous disorder in women of reproductive age, the exact etiology of which remains unknown. To unravel the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Using microarray analysis, 1188 differentially expressed genes, including 671 upregulated and 517 downregulated genes, were identified in ovaries from PNA mice. Five differentially expressed genes (Aldh1a7, Bhmt, Mtr, Nrcam, Ptprg) were validated, and decreased MTR expression was shown in ovaries of PNA mice...
2017: PloS One
https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#7
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29194039/validation-of-a-high-performance-liquid-chromatography-method-for-thiopurine-s-methyltransferase-activity-in-whole-blood-using-6-mercaptopurine-as-substrate
#8
Hannah Rieger, Patrik Schmidt, Elke Schaeffeler, Manabu Abe, Mira Schiffhauer, Matthias Schwab, Nicolas von Ahsen, Gabriela Zurek, Hartmut Kirchherr, Maria Shipkova, Eberhard Wieland
BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely performed in patients to adjust drug therapy. METHODS: We further optimized a previously established high-performance liquid chromatography (HPLC) method by measuring TPMT activity in whole blood instead of isolated erythrocytes, which is based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S-adenosyl-methionine as methyl donor...
December 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29180119/cyclopropane-fatty-acid-synthesis-affects-cell-shape-and-acid-resistance-in-leishmania-mexicana
#9
Wei Xu, Sumit Mukherjee, Yu Ning, Fong-Fu Hsu, Kai Zhang
Cyclopropane fatty acid synthase (CFAS) catalyzes the transfer of a methylene group from S-adenosyl methionine to an unsaturated fatty acid, generating a cyclopropane fatty acid (CFA). The gene encoding CFAS is present in many bacteria and several Leishmania spp. including Leishmania mexicana, Leishmania infantum and Leishmania braziliensis. In this study, we characterized the CFAS-null and -overexpression mutants in L. mexicana, the causative agent for cutaneous leishmaniasis in Mexico and central America...
November 24, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29176927/conceptualizing-eukaryotic-metabolic-sensing-and-signaling
#10
Sunil Laxman
For almost all cells, nutrient availability, from glucose to amino acids, dictates their growth or developmental programs. This nutrient availability is closely coupled to the overall intracellular metabolic state of the cell. Therefore, cells have evolved diverse, robust and versatile modules to sense intracellular metabolic states, activate signaling outputs and regulate outcomes to these states. Yet, signaling and metabolism have been viewed as important but separate. This short review attempts to position aspects of intracellular signaling from a metabolic perspective, highlighting how conserved, core principles of metabolic sensing and signaling can emerge from an understanding of metabolic regulation...
March 2017: Journal of the Indian Institute of Science
https://www.readbyqxmd.com/read/29157356/effect-of-exogenous-progesterone-on-embryo-size-and-ewe-uterine-gene-expression-in-an-ovine-dam-size-model-of-maternal-constraint
#11
Lisanne M Fermin, Sarah J Pain, Patrick C H Morel, Kristene R Gedye, Paul R Kenyon, Hugh T Blair
Progesterone (P4), acting via its receptor, regulates uterine function and histotroph production, which are crucial to embryo growth. This study aimed to examine exogenous P4 effects on embryo size and differential endometrial gene expression at Day 19 of gestation using a 'dam size' sheep model of maternal constraint. Purebred Suffolk (S, genotypically large) embryos were transferred into recipient groups of Cheviot (C, genotypically small) or Suffolk ewes that had, or had not, been pre-treated with P4 from Days 0 to 6 of pregnancy...
November 21, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29116772/n-6-allyladenosine-a-new-small-molecule-for-rna-labeling-identified-by-mutation-assay
#12
Xiao Shu, Qing Dai, Tong Wu, Ian R Bothwell, Yanan Yue, Zezhou Zhang, Jie Cao, Qili Fei, Minkui Luo, Chuan He, Jianzhao Liu
RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report N(6)-allyladenosine (a(6)A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a(6)A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mammalian cells. We also show that human RNA N(6)-methyladenosine (m(6)A) methyltransferases METTL3/METTL14 can work with a synthetic cofactor, namely allyl-SAM (S-adenosyl methionine with methyl replaced by allyl) in order to site-specifically install an allyl group to the N(6)-position of A within specific sequence to generate a(6)A-labeled RNAs...
November 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29091948/selection-and-validation-of-appropriate-reference-genes-for-quantitative-real-time-pcr-analysis-in-salvia-hispanica
#13
Rahul Gopalam, Sunny D Rupwate, Ajay W Tumaney
Quantitative real-time polymerase chain reaction (qRT-PCR) has become the most popular choice for gene expression studies. For accurate expression analysis, it is pertinent to select a stable reference gene to normalize the data. It is now known that the expression of internal reference genes varies considerably during developmental stages and under different experimental conditions. For Salvia hispanica, an economically important oilseed crop, there are no reports of stable reference genes till date. In this study, we chose 13 candidate reference genes viz...
2017: PloS One
https://www.readbyqxmd.com/read/29080162/determination-of-s-adenosylmethionine-decarboxylase-activity-in-plants
#14
Antonio F Tiburcio, Rubén Alcázar
The synthesis of spermidine, spermine and thermospermine requires the addition of aminopropyl groups from decarboxylated S-adenosyl-methionine (dSAM). The synthesis of dSAM is catalyzed by S-adenosylmethionine decarboxylase. dSAM levels are usually low, which constitutes a rate-limiting factor in the synthesis of polyamines. In this chapter, we provide a protocol for the determination of SAMDC activity in plants through the detection of radiolabelled CO2 released during the SAMDC reaction.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29020412/emerging-role-of-one-carbon-metabolism-and-dna-methylation-enrichment-on-%C3%AE-containing-gabaa-receptor-expression-in-the-cerebellum-of-subjects-with-alcohol-use-disorders-aud
#15
Eleonora Gatta, James Auta, David P Gavin, Dulal K Bhaumik, Dennis R Grayson, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamatergic granule cells. Here, we studied whether chronic alcohol consumption induces changes in GABAA receptor subunit expression and whether these changes are associated with alterations in epigenetic mechanisms via DNA methylation...
August 19, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28973912/structural-basis-underlying-complex-assembly-and-conformational-transition-of-the-type-i-r-m-system
#16
Yan-Ping Liu, Qun Tang, Jie-Zhong Zhang, Li-Fei Tian, Pu Gao, Xiao-Xue Yan
Type I restriction-modification (R-M) systems are multisubunit enzymes with separate DNA-recognition (S), methylation (M), and restriction (R) subunits. Despite extensive studies spanning five decades, the detailed molecular mechanisms underlying subunit assembly and conformational transition are still unclear due to the lack of high-resolution structural information. Here, we report the atomic structure of a type I MTase complex (2M+1S) bound to DNA and cofactor S-adenosyl methionine in the "open" form. The intermolecular interactions between M and S subunits are mediated by a four-helix bundle motif, which also determines the specificity of the interaction...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28955359/purification-and-in-vitro-activity-of-mitochondria-targeted-nitrogenase-cofactor-maturase-nifb
#17
Stefan Burén, Xi Jiang, Gema López-Torrejón, Carlos Echavarri-Erasun, Luis M Rubio
Active NifB is a milestone in the process of engineering nitrogen fixing plants. NifB is an extremely O2-sensitive S-adenosyl methionine (SAM)-radical enzyme that provides the key metal cluster intermediate (NifB-co) for the biosyntheses of the active-site cofactors of all three types of nitrogenases. NifB and NifB-co are unique to diazotrophic organisms. In this work, we have expressed synthetic codon-optimized versions of NifB from the γ-proteobacterium Azotobacter vinelandii and the thermophilic methanogen Methanocaldococcus infernus in Saccharomyces cerevisiae and in Nicotiana benthamiana...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28949991/structural-insights-into-substrate-selectivity-of-ribosomal-rna-methyltransferase-rlmcd
#18
Yiyang Jiang, Fudong Li, Jihui Wu, Yunyu Shi, Qingguo Gong
RlmCD has recently been identified as the S-adenosyl methionine (SAM)-dependent methyltransferase responsible for the formation of m5U at U747 and U1939 of 23S ribosomal RNA in Streptococcus pneumoniae. In this research, we determine the high-resolution crystal structures of apo-form RlmCD and its complex with SAH. Using an in-vitro methyltransferase assay, we reveal the crucial residues for its catalytic functions. Furthermore, structural comparison between RlmCD and its structural homologue RumA, which only catalyzes the m5U1939 in Escherichia coli, implicates that a unique long linker in the central domain of RlmCD is the key factor in determining its substrate selectivity...
2017: PloS One
https://www.readbyqxmd.com/read/28944535/overexpression-of-sbmyb60-in-sorghum-bicolor-impacts-both-primary-and-secondary-metabolism
#19
Erin D Scully, Tammy Gries, Nathan A Palmer, Gautam Sarath, Deanna L Funnell-Harris, Lisa Baird, Paul Twigg, Javier Seravalli, Thomas E Clemente, Scott E Sattler
Few transcription factors have been identified in C4 grasses that either positively or negatively regulate monolignol biosynthesis. Previously, the overexpression of SbMyb60 in sorghum (Sorghum bicolor) has been shown to induce monolignol biosynthesis, which leads to elevated lignin deposition and altered cell wall composition. To determine how SbMyb60 overexpression impacts other metabolic pathways, RNA-Seq and metabolite profiling were performed on stalks and leaves. 35S::SbMyb60 was associated with the transcriptional activation of genes involved in aromatic amino acid, S-adenosyl methionine (SAM) and folate biosynthetic pathways...
September 25, 2017: New Phytologist
https://www.readbyqxmd.com/read/28939775/translesion-synthesis-dna-polymerases-promote-error-free-replication-through-the-minor-groove-dna-adduct-3-deaza-3-methyladenine
#20
Jung-Hoon Yoon, Jayati Roy Choudhury, Jeseong Park, Satya Prakash, Louise Prakash
N3-Methyladenine (3-MeA) is formed in DNA by reaction with S-adenosylmethionine, the reactive methyl donor, and by reaction with alkylating agents. 3-MeA protrudes into the DNA minor groove and strongly blocks synthesis by replicative DNA polymerases (Pols). However, the mechanisms for replicating through this lesion in human cells remain unidentified. Here we analyzed the roles of translesion synthesis (TLS) Pols in the replication of 3-MeA-damaged DNA in human cells. Because 3-MeA has a short half-life in vitro, we used the stable 3-deaza analog, 3-deaza-3-methyladenine (3-dMeA), which blocks the DNA minor groove similarly to 3-MeA...
November 10, 2017: Journal of Biological Chemistry
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