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https://www.readbyqxmd.com/read/28318037/deoxycytidine-and-deoxythymidine-treatment-for-thymidine-kinase-2-deficiency
#1
Carlos Lopez-Gomez, Rebecca J Levy, Maria J Sanchez-Quintero, Marti Juanola-Falgarona, Emanuele Barca, Beatriz Garcia-Diaz, Saba Tadesse, Caterina Garone, Michio Hirano
OBJECTIVE: Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene TK2 cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, dCMP and dTMP, prolongs the lifespan of Tk2-deficient (Tk2(-/-) ) mice by 2-3 fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: 1) deoxynucleosides might be the major active agents and 2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28290905/-therapy-of-high-risk-patients-after-decompensation-of-heart-failure-under-nt-probnp-control-main-results
#2
A A Skvortsov, D E Koshkina, O Yu Narusov, V N Protasov, V P Masenko, S N Tereshchenko
AIM: to compare efficacy of treatment of high risk patients after acute decompensation (AD) of chronic heart failure (CHF) based on monitoring of NT-proBNP concentration and standard treatment. MATERIAL AND METHODS: Patients (n=100) with class III-IV CHF and left ventricular ejection fraction (LV EF) <40% due to ischemic heart disease (IHD), dilated cardiomyopathy (DCMP), or arterial hypertension (AH) after compensation of HF before discharge were distributed into groups of low (NT-proBNP <1400 picog/ml, n=30) or high (NT-proBNP more or equal 1400 picog/ml, n=70) risk...
July 2016: Kardiologiia
https://www.readbyqxmd.com/read/28290856/-chronic-heart-failure-with-preserved-systolic-function-and-reversible-dilatation-of-cardiac-chambers
#3
O V Blagova, S V Volkov, A V Nedostup, A O Korobkov, I V Mostovoy, N G Sergushina, N V Gagarina, E A Mershina
Diagnosis of dilation (D) cardiomyopathy (CMP) requires exclusion not only of inflammatory and genetically determined forms but also of some rare diseases. This 51 year old patient with history of moderate arterial hypertension approached a cardiologist because of new onset atrial fibrillation and dyspnea. Echocardiography detected dilation of all cardiac chambers with relatively preserved ejection fraction, causing suspicion of DCMP. Among conditions excluded were coronary atherosclerosis, congenital heart defect with left to right shunt, primary pulmonary hypertension, pulmonary embolism, hypertensive heart, tachycardia induced CMP, arrhythmogenic right ventricular dysplasia, noncompaction myocardium...
June 2016: Kardiologiia
https://www.readbyqxmd.com/read/28271879/formation-and-determination-of-endogenous-methylated-nucleotides-in-mammals-by-chemical-labeling-coupled-with-mass-spectrometry-analysis
#4
Huan Zeng, Chu-Bo Qi, Ting Liu, Hua-Ming Xiao, Qing-Yun Cheng, Han-Peng Jiang, Bifeng Yuan, Yu-Qi Feng
5-Methylcytosine (5-mC) is an important epigenetic mark that plays critical roles in a variety of cellular pro-cesses. To properly exert physiological functions, the distribution of 5-mC needed to be tightly controlled in both DNA and RNA. In addition to methyltransferase-mediated DNA and RNA methylation, pre-methylated nucleotides can be potentially incorporated into DNA and RNA during replication and transcription. To exclude the pre-modified nucleotides into DNA and RNA, endogenous 5-methyl-2'-deoxycytidine monophosphate (5-Me-dCMP) generated from nucleic acids metabolism can be enzymatically deaminated to thymidine mono-phosphate (TMP)...
March 8, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28202452/entire-plastid-phylogeny-of-the-carrot-genus-daucus-apiaceae-concordance-with-nuclear-data-and-mitochondrial-and-nuclear-dna-insertions-to-the-plastid
#5
David M Spooner, Holly Ruess, Massimo Iorizzo, Douglas Senalik, Philipp Simon
PREMISE OF THE STUDY: We explored the phylogenetic utility of entire plastid DNA sequences in Daucus and compared the results with prior phylogenetic results using plastid and nuclear DNA sequences. METHODS: We used Illumina sequencing to obtain full plastid sequences of 37 accessions of 20 Daucus taxa and outgroups, analyzed the data with phylogenetic methods, and examined evidence for mitochondrial DNA transfer to the plastid (DcMP). KEY RESULTS: Our phylogenetic trees of the entire data set were highly resolved, with 100% bootstrap support for most of the external and many of the internal clades, except for the clade of D...
February 15, 2017: American Journal of Botany
https://www.readbyqxmd.com/read/28198522/cardiovascular-drug-utilization-post-implant-is-related-to-clinical-outcome-in-heart-failure-patients-receiving-cardiac-resynchronization-therapy
#6
Zoltan Bakos, Christian Reitan, Anna Werther-Evaldsson, Anders Roijer, Pyotr PLatonov, Rasmus Borgquist
BACKGROUND: In select patients with heart failure, cardiac resynchronization therapy (CRT) is the most common complementary treatment besides medical treatment. We aimed to assess the association between post CRT-implant changes in cardiovascular medication and cardiovascular mortality and heart failure hospitalization. METHODS: 211 patients on optimal medical therapy eligible for CRT were retrospectively included in this study (72 ± 7 years, 80% male, 66% left bundle branch block [LBBB], 48% dilated cardiomyopathy [DCMP]) and investigated at baseline and after 6 months ...
February 15, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28150748/efficient-n-tailing-of-blunt-dna-ends-by-moloney-murine-leukemia-virus-reverse-transcriptase
#7
Yoshiyuki Ohtsubo, Yuji Nagata, Masataka Tsuda
Moloney murine leukemia virus reverse transcriptase (MMLV-RT) is a widely used enzyme for cDNA synthesis. Here we show that MMLV-RT has a strong template-independent polymerase activity using blunt DNA ends as substrate that generates 3' overhangs of A, C, G, or T. Nucleotides were appended efficiently in the order A > G > T > C, and tail lengths varied from 4 to 5, 2 to 7, 2 to 4, and 2 to 3 for A, C, G, and T, respectively. The activity was so strong that nearly all our test DNA ends were appended with at least one A, C, G, or T...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070248/childhood-cardiomyopathies-a-study-in-tertiary-care-hospital-in-upper-egypt
#8
Mohamed Abd Elaal Bakeet, Montaser Mohamed Mohamed, Ahmed Ahmed Allam, Rania Gamal
INTRODUCTION: Cardiomyopathy (CMP) is defined by the World Health Organization (WHO) as a disease of the myocardium associated with cardiac dysfunction. An understanding of CMP is very important, as it is a common cause of heart failure in children, and the most common indication for heart transplantation in children older than one year, but data on CMP in Egypt are scarce. The aim of this study was to determine the number, risk factors, clinical presentation, complications and outcome of different types of childhood cardiomyopathies in Sohag University Hospital...
November 2016: Electronic Physician
https://www.readbyqxmd.com/read/28000775/structural-basis-of-the-substrate-preference-towards-cmp-for-a-thymidylate-synthase-mila-involved-in-mildiomycin-biosynthesis
#9
Gong Zhao, Cheng Chen, Wei Xiong, Tuling Gao, Zixin Deng, Geng Wu, Xinyi He
Modified pyrimidine monophosphates such as methyl dCMP (mdCMP), hydroxymethyl dUMP (hmdUMP) and hmdCMP in some phages are synthesized by a large group of enzymes termed as thymidylate synthases (TS). Thymidylate is a nucleotide required for DNA synthesis and thus TS is an important drug target. In the biosynthetic pathway of the nucleoside fungicide mildiomycin isolated from Streptomyces rimofaciens ZJU5119, a cytidylate (CMP) hydroxymethylase, MilA, catalyzes the conversion of CMP into 5'-hydroxymethyl CMP (hmCMP) with an efficiency (kcat/KM) of 5-fold faster than for deoxycytidylate (dCMP)...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905387/-dilated-cardiomyopathy-as-a-cause-of-ischemic-stroke
#10
S G Zhdanova, S S Petrikov, G R Ramazanov, L T Khamidova, I S Aliev, Z O Sarkisyan
Dilated cardiomyopathy (DCMP) is a disease of the myocardium characterized by the dilatation of heart cavities with the development of systolic dysfunction but without a decrease in the thickness of the myocardium. DCMP is a frequent cause of cardioembolic syndrome, in particular cardioembolic ischemic stroke (CES). A case of a patient with DCMP after CES is presented.
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27820863/pyrimidine-salvage-enzymes-are-essential-for-de-novo-biosynthesis-of-deoxypyrimidine-nucleotides-in-trypanosoma-brucei
#11
Christopher Leija, Filipa Rijo-Ferreira, Lisa N Kinch, Nick V Grishin, Nicole Nischan, Jennifer J Kohler, Zeping Hu, Margaret A Phillips
The human pathogenic parasite Trypanosoma brucei possess both de novo and salvage routes for the biosynthesis of pyrimidine nucleotides. Consequently, they do not require salvageable pyrimidines for growth. Thymidine kinase (TK) catalyzes the formation of dTMP and dUMP and is one of several salvage enzymes that appear redundant to the de novo pathway. Surprisingly, we show through analysis of TK conditional null and RNAi cells that TK is essential for growth and for infectivity in a mouse model, and that a catalytically active enzyme is required for its function...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27730780/dobutamine-stress-echocardiography-need-for-a-better-gold-standard
#12
Ankush Sachdeva, Biswajit Paul
Dobutamine stress echocardiography (DSE) has come a long way as establishing itself as a feasible, safe, effective, relatively cheaper non-invasive technique to detect population suffering from coronary artery disease (CAD) and following up patients post revascuralization. Besides these DSE is commonly used to diagnose low gradient, low flow true severe aortic stenosis (AS); differentiating it from pseudo- AS and to follow up patients with dilated cardiomyopathy (DCMP). Various non-invasive techniques have different sensitivity and specificity to accurately judge a viable myocardium and to accurately detect the improvement in regional wall motion abnormality (RWMA) post-revascularization, leading to an overall increase in left ventricular ejection fraction (LVEF)...
February 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27728067/multidrug-combination-therapy-favours-dcmp-survival-rates
#13
Harsh Kumar Garg
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27683219/rev1-is-a-base-excision-repair-enzyme-with-5-deoxyribose-phosphate-lyase-activity
#14
Rajendra Prasad, Vladimir Poltoratsky, Esther W Hou, Samuel H Wilson
Rev1 is a member of the Y-family of DNA polymerases and is known for its deoxycytidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. In light of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cells treated with a base excision repair-inducing agent, we questioned whether Rev1 could also be involved in base excision repair (BER)...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27660390/impact-of-ribonucleotide-backbone-on-translesion-synthesis-and-repair-of-7-8-dihydro-8-oxoguanine
#15
Akira Sassa, Melike Çağlayan, Yesenia Rodriguez, William A Beard, Samuel H Wilson, Takehiko Nohmi, Masamitsu Honma, Manabu Yasui
Numerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols κ and η in vitro The primer extension reaction catalyzed by human replicative pol α was strongly blocked by 8-oxo-rG...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27611246/replicative-bypass-of-o-2-alkylthymidine-lesions-in-vitro
#16
Nicole L Williams, Pengcheng Wang, Yinsheng Wang
DNA alkylation represents a major type of DNA damage and is generally unavoidable due to ubiquitous exposure to various exogenous and endogenous sources of alkylating agents. Among the alkylated DNA lesions, O(2)-alkylthymidines (O(2)-alkyldT) are known to be persistent and poorly repaired in mammalian systems and have been shown to accumulate in the esophagus, lung, and liver tissue of rats treated with tobacco-specific N-nitrosamines, i.e., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN)...
October 17, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27547471/noncompaction-and-dilated-cardiomyopathy-in-a-patient-with-schizophrenia
#17
Josef Finsterer, Claudia Stöllberger
Objectives. Psychosis and left ventricular hypertrabeculation (or noncompaction) (LVHT) have not been described in the same patient. Here we report a patient with a long-term history of schizophrenia who was later diagnosed with dilated cardiomyopathy (dCMP) and LVHT. Case Report. A 47-year-old Caucasian male developed nondifferentiated schizophrenia at the age of 26 y. Since the age of 33 y he was regularly drinking alcohol. At the age of 47 y he developed heart failure. Transthoracic echocardiography showed an enlarged left ventricle, reduced systolic function, and surprisingly LVHT in the apical segment...
2016: Case Reports in Cardiology
https://www.readbyqxmd.com/read/27462586/dilated-cardiomyopathy-with-graves-disease-in-a-young-child
#18
Yu Jung Choi, Jun Ho Jang, So Hyun Park, Jin-Hee Oh, Dae Kyun Koh
Graves disease (GD) can lead to complications such as cardiac arrhythmia and heart failure. Although dilated cardiomyopathy (DCMP) has been occasionally reported in adults with GD, it is rare in children. We present the case of a 32-month-old boy with DCMP due to GD. He presented with irritability, vomiting, and diarrhea. He also had a history of weight loss over the past few months. On physical examination, he had tachycardia without fever, a mild diffuse goiter, and hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary edema, while the echocardiography revealed a dilated left ventricle with an ejection fraction (EF) of 28%...
June 2016: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27404553/bypass-of-mutagenic-o-6-carboxymethylguanine-dna-adducts-by-human-y-and-b-family-polymerases
#19
Michael H Räz, Hannah R Dexter, Christopher L Millington, Barbara van Loon, David M Williams, Shana J Sturla
The generation of chemical alkylating agents from nitrosation of glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O(6)-carboxymethylguanine (O(6)-CMG) is a product of DNA alkylation derived from nitrosated glycine. Although the tendency of the structurally related adduct O(6)-methylguanine to code for the misincoporation of TTP during DNA replication is well-established, the impact of the presence of the O(6)-CMG adduct in a DNA template on the efficiency and fidelity of translesion DNA synthesis (TLS) by human DNA polymerases (Pols) has hitherto not been described...
September 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27377385/mechanism-of-the-allosteric-regulation-of-streptococcus-mutans-2-deoxycytidylate-deaminase
#20
Yanhua Li, Zhen Guo, Li Jin, Deqiang Wang, Zengqiang Gao, Xiaodong Su, Haifeng Hou, Yuhui Dong
In cells, dUMP is the intermediate precursor of dTTP in its synthesis during deoxynucleotide metabolism. In Gram-positive bacteria and eukaryotes, zinc-dependent deoxycytidylate deaminases (dCDs) catalyze the conversion of dCMP to dUMP. The activity of dCD is allosterically activated by dCTP and inhibited by dTTP. Here, the crystal structure of Streptococcus mutans dCD (SmdCD) complexed with dTTP is presented at 2.35 Å resolution, thereby solving the first pair of activator-bound and inhibitor-bound structures from the same species to provide a more definitive description of the allosteric mechanism...
July 2016: Acta Crystallographica. Section D, Structural Biology
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