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https://www.readbyqxmd.com/read/29783192/interaction-of-dna-and-mononucleotides-with-theophylline-investigated-using-electrochemical-biosensors-and-biosensing
#1
Katarína Nemčeková, Ján Labuda, Viktor Milata, Jana Blaškovičová, Jozef Sochr
The understanding of DNA-drug interaction mechanism is among the important aspects of biological studies for drug design, discovery and pharmaceutical development processes. Published rather detailed FTIR and UV-visible spectroscopic studies on the interactions of theophylline, theobromine and caffeine with calf thymus DNA have shown effective binding of these methylxanthine derivatives to DNA and RNA involving H-bonds. However, to our knowledge, there is no such investigation using electrochemical approach...
May 3, 2018: Bioelectrochemistry
https://www.readbyqxmd.com/read/29782554/hijacking-of-multiple-phospholipid-biosynthetic-pathways-and-induction-of-membrane-biogenesis-by-a-picornaviral-3cd-protein
#2
Sravani Banerjee, David Aponte-Diaz, Calvin Yeager, Suresh D Sharma, Gang Ning, Hyung S Oh, Qingxia Han, Masato Umeda, Yuji Hara, Robert Y L Wang, Craig E Cameron
RNA viruses induce specialized membranous structures for use in genome replication. These structures are often referred to as replication organelles (ROs). ROs exhibit distinct lipid composition relative to other cellular membranes. In many picornaviruses, phosphatidylinositol-4-phosphate (PI4P) is a marker of the RO. Studies to date indicate that the viral 3A protein hijacks a PI4 kinase to induce PI4P by a mechanism unrelated to the cellular pathway, which requires Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1, GBF1, and ADP ribosylation factor 1, Arf1...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782187/effects-of-maternal-vitamin-d-supplementation-on-the-maternal-and-infant-epigenome
#3
Cindy M Anderson, Shannon L Gillespie, Doria K Thiele, Jody L Ralph, Joyce E Ohm
INTRODUCTION: Mothers and infants are at high risk for inadequate vitamin D status. Mechanisms by which vitamin D may affect maternal and infant DNA methylation are poorly understood. OBJECTIVE: This study quantified the effects of vitamin D3 supplementation on DNA methylation in pregnant and lactating women and their breastfed infants. MATERIALS AND METHODS: In this randomized controlled pilot study, pregnant women received vitamin D3 400 international units (IU) (n = 6; control) or 3,800 IU (n = 7; intervention) daily from late second trimester through 4-6 weeks postpartum...
May 21, 2018: Breastfeeding Medicine: the Official Journal of the Academy of Breastfeeding Medicine
https://www.readbyqxmd.com/read/29780538/competition-between-li-and-na-in-sodium-transporters-and-receptors-which-na-binding-sites-are-therapeutic-li-targets
#4
Todor Dudev, Karine Mazmanian, Carmay Lim
Sodium (Na+ ) acts as an indispensable allosteric regulator of the activities of biologically important neurotransmitter transporters and G-protein coupled receptors (GPCRs), which comprise well-known drug targets for psychiatric disorders and addictive behavior. How selective these allosteric Na+ -binding sites are for the cognate cation over abiogenic Li+ , a first-line drug to treat bipolar disorder, is unclear. Here, we reveal how properties of the host protein and its binding cavity affect the outcome of the competition between Li+ and Na+ for allosteric binding sites in sodium transporters and receptors...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780486/glucose-nucleobase-pairs-within-dna-impact-of-hydrophobicity-alternative-linking-unit-and-dna-polymerase-nucleotide-insertion-studies
#5
Empar Vengut-Climent, Pablo Peñalver, Ricardo Lucas, Irene Gómez-Pinto, Anna Aviñó, Alicia M Muro-Pastor, Elsa Galbis, M Violante de Paz, Célia Fonseca Guerra, F Matthias Bickelhaupt, Ramón Eritja, Carlos González, Juan Carlos Morales
Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside-RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs...
April 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780475/development-of-microfluidic-platforms-for-the-synthesis-of-metal-complexes-and-evaluation-of-their-dna-affinity-using-online-fret-melting-assays
#6
Viktoria Rakers, Paolo Cadinu, Joshua B Edel, Ramon Vilar
Guanine-rich DNA sequences can fold into quadruple-stranded structures known as G-quadruplexes. These structures have been proposed to play important biological roles and have been identified as potential drug targets. As a result, there is increasing interest in developing small molecules that can bind to G-quadruplexes. So far, these efforts have been mostly limited to conventional batch synthesis. Furthermore, no quick on-line method to assess new G-quadruplex binders has been developed. Herein, we report on two new microfluidic platforms to: (a) readily prepare G-quadruplex binders (based on metal complexes) in flow, quantitatively and without the need for purification before testing; (b) a microfluidic platform (based on FRET melting assays of DNA) that enables the real-time and on-line assessment of G-quadruplex binders in continuous flow...
April 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29778492/tanovea%C3%A2-for-the-treatment-of-lymphoma-in-dogs
#7
REVIEW
Erik De Clercq
Tanovea® (first named GS-9219, then VDC-1101, generic name: rabacfosadine) is a pro-prodrug or "double" prodrug of PMEG [9-(2-phosphonylmethoxyethyl)guanine], which has been conditionally approved by the US FDA (Food and Drug Administration) for the treatment of lymphoma in dogs. Tanovea has been demonstrated to be effective against non-Hodgkin's lymphoma (NHL) in dogs, as well as canine cutaneous T-cell lymphoma, spontaneous canine multiple myeloma, naïve canine multicentric lymphoma and relapsed canine B-cell lymphoma...
May 17, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29777899/congenital-dyshormonogenic-hypothyroidism-with-goiter-caused-by-a-sodium-iodide-symporter-slc5a5-mutation-in-a-family-of-shih-tzu-dogs
#8
E A Soler Arias, V A Castillo, J D Garcia, J C Fyfe
An iodide transport defect (ITD) in the thyroid gland was determined to cause congenital dyshormonogenic hypothyroidism with goiter (CDHG) in 2 members of a family of Shih-Tzu dogs. Strikingly, both dogs were also diagnosed with dilated cardiomyopathy at 24 and 1.5 mo of age. The only sign of hypothyroidism was a moderate growth delay in the adult dog. The ITD was recognized by the absence of uptake of technetium-99m in the salivary glands (sg) and goiter observed by scintigraphy. In the same scan, radiopharmaceutical uptake was found in the anterior mediastinum of both dogs and in the right axillary lymph node in the oldest dog...
April 24, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29777239/inference-about-causation-between-body-mass-index-and-dna-methylation-in-blood-from-a-twin-family-study
#9
Shuai Li, Ee Ming Wong, Minh Bui, Tuong L Nguyen, Ji-Hoon Eric Joo, Jennifer Stone, Gillian S Dite, Pierre-Antoine Dugué, Roger L Milne, Graham G Giles, Richard Saffery, Melissa C Southey, John L Hopper
BACKGROUND: Several studies have reported DNA methylation in blood to be associated with body mass index (BMI), but few have investigated causal aspects of the association. We used a twin family design to assess this association at two life points and applied a novel analytical approach to appraise the evidence for causality. METHODS: The methylation profile of DNA from peripheral blood was measured for 479 Australian women from 130 twin families. Linear regression was used to estimate the associations of DNA methylation at ~410,000 cytosine-guanine dinucleotides (CpGs), and of the average DNA methylation at ~20,000 genes, with current BMI, BMI at age 18-21 years, and the change between the two (BMI change)...
May 17, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29776603/regulation-of-g-protein-%C3%AE-%C3%AE-signaling
#10
Kanishka Senarath, Dinesh Kankanamge, Saroopa Samaradivakara, Kasun Ratnayake, Mithila Tennakoon, Ajith Karunarathne
Heterotrimeric guanine nucleotide-binding proteins (G proteins) deliver external signals to the cell interior, upon activation by the external signal stimulated G protein-coupled receptors (GPCRs).While the activated GPCRs control several pathways independently, activated G proteins control the vast majority of cellular and physiological functions, ranging from vision to cardiovascular homeostasis. Activated GPCRs dissociate GαGDPβγ heterotrimer into GαGTP and free Gβγ. Earlier, GαGTP was recognized as the primary signal transducer of the pathway and Gβγ as a passive signaling modality that facilitates the activity of Gα...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29775996/interplay-between-adenylate-metabolizing-enzymes-and-amp-activated-protein-kinase
#11
REVIEW
Marcella Camici, Simone Allegrini, Maria Grazia Tozzi
Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps. The salvage pathways utilize hypoxanthine, guanine and adenine to generate the corresponding mononucleotides...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29773874/mutations-in-six-nephrosis-genes-delineate-a-pathogenic-pathway-amenable-to-treatment
#12
Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A Lawson, Weizhen Tan, Tobias Hermle, Jillian K Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A Braun, Heon Yung Gee, David Schapiro, Amar J Majmundar, Carolin E Sadowski, Werner L Pabst, Ankana Daga, Amelie T van der Ven, Johanna M Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A Soliman, Shrikant M Mane, Lewis Kaufman, Douglas R Lowy, Mohamad A Jairajpuri, Richard P Lifton, York Pei, Martin Zenker, Shigeo Kure, Friedhelm Hildebrandt
No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773556/prdx1-and-mth1-cooperate-to-prevent-ros-mediated-inhibition-of-telomerase
#13
Wareed Ahmed, Joachim Lingner
Telomerase counteracts telomere shortening and cellular senescence in germ, stem, and cancer cells by adding repetitive DNA sequences to the ends of chromosomes. Telomeres are susceptible to damage by reactive oxygen species (ROS), but the consequences of oxidation of telomeres on telomere length and the mechanisms that protect from ROS-mediated telomere damage are not well understood. In particular, 8-oxoguanine nucleotides at 3' ends of telomeric substrates inhibit telomerase in vitro, whereas, at internal positions, they suppress G-quadruplex formation and were therefore proposed to promote telomerase activity...
May 17, 2018: Genes & Development
https://www.readbyqxmd.com/read/29772375/duplex-functional-g-quadruplex-nmm-fluorescent-probe-for-label-free-detection-of-lead-ii-and-mercury-ii-ions
#14
Qian Zhu, Lanhua Liu, Yunpeng Xing, Xiaohong Zhou
To meet the severe water pollution status, multi-target biosensor becomes one of research focus. We herein report a novel duplex functional fluorescent biosensor for the label-free and separate detection of Pb2+ and Hg2+ with high sensitivity and selectivity. A K+ -induced fluorescent G-quadruplex probe was assembled by a guanine-rich sequence (AGRO100) and N-methyl mesoporphyrin IX(NMM). It changed into a more stably non-fluorescent G-quadruplex structure and a hairpin-like structure upon binding Pb2+ and Hg2+ ions, respectively...
May 1, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29772239/small-gtpase-r-ras-participates-in-neural-tube-formation-in-zebrafish-embryonic-spinal-cord
#15
Shinya Ohata, Hideko Uga, Hitoshi Okamoto, Toshiaki Katada
Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29771499/guanine-and-8-azaguanine-in-anomeric-dna-hybrid-base-pairs-stability-fluorescence-sensing-and-efficient-mismatch-discrimination-with-%C3%AE-d-nucleosides
#16
Jiang Liu, Sachin Asaram Ingale, Frank Seela
The α-anomers of 8-aza-2'-deoxyguanosine (αGd*) and 2'-deoxyguanosine (αGd) were site-specifically incorporated in 12-mer duplexes opposite to the four canonical DNA constituents dA, dG, dT and dC. Oligodeoxyribonucleotides containing αGd* display significant fluorescence at slightly elevated pH (8.0). Oligodeoxyribonucleotides incorporating β-anomeric 8-aza-2'-deoxyguanosine (Gd*) and canonical dG were studied for comparison. For αGd* synthesis, an efficient purification of anomeric 8-azaguanine nucleosides was developed on the basis of protected intermediates and a new αGd* phosphoramidite was prepared...
May 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29769549/detection-of-chikungunya-virus-dna-using-two-dimensional-mos-2-nanosheets-based-disposable-biosensor
#17
Chaitali Singhal, Manika Khanuja, Nahid Chaudhary, C S Pundir, Jagriti Narang
Development of platforms for a reliable, rapid, sensitive and selective detection of chikungunya virus (CHIGV) is the need of the hour in developing countries. To the best of our knowledge, there are no reports available for the electrochemical detection of CHIGVDNA. Therefore, we aim at developing a biosensor based on molybdenum disulphide nanosheets (MoS2 NSs) for the point-of-care diagnosis of CHIGV. Briefly, MoS2 NSs were synthesized by chemical route and characterized using scanning electron microscopy, transmission electron microscopy, UV-Vis spectroscopy, Raman spectroscopy and X-Ray Diffraction...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769144/contributions-of-the-rhoa-guanine-nucleotide-exchange-factor-net1-to-polyoma-middle-t-antigen-mediated-mammary-gland-tumorigenesis-and-metastasis
#18
Yan Zuo, Arzu Ulu, Jeffrey T Chang, Jeffrey A Frost
BACKGROUND: The RhoA activating protein Net1 contributes to breast cancer cell proliferation, motility, and invasion in vitro, yet little is known about its roles in mammary gland tumorigenesis and metastasis. METHODS: Net1 knockout (KO) mice were bred to mice with mammary gland specific expression of the polyoma middle T antigen (PyMT) oncogene. Mammary gland tumorigenesis and lung metastasis were monitored. Individual tumors were assessed for proliferation, apoptosis, angiogenesis, RhoA activation, and activation of PyMT-dependent signaling pathways...
May 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29767962/targeting-photo-induced-dna-destruction-by-ru-ii-tetraazaphenathrene-in-live-cells-by-signal-peptide
#19
Christopher S Burke, Aisling Byrne, Tia E Keyes
Exploiting NF-κB transcription factor peptide conjugation, a Ru(II)-bis-tap complex (tap = 1,4,5,8-tetraazaphenanthrene) was targeted specifically to the nuclei of live mammalian (HeLa and CHO) cells for the first time. DNA binding in the nucleus of live cells was evident from gradual extinction of the metal complex luminescence after it had crossed the nuclear envelope, attributed to guanine quenching of the ruthenium emission via photoinduced electron transfer. Resonance Raman imaging confirmed that the complex remained in the nucleus after emission is extinguished...
May 16, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29767200/nmr-analyses-on-n-hydroxymethylated-nucleobases-implications-for-formaldehyde-toxicity-and-nucleic-acid-demethylases
#20
S Shishodia, D Zhang, A H El-Sagheer, T Brown, T D W Claridge, C J Schofield, R J Hopkinson
Formaldehyde is produced in cells by enzyme-catalysed demethylation reactions, including those occurring on N-methylated nucleic acids. Formaldehyde reacts with nucleobases to form N-hydroxymethylated adducts that may contribute to its toxicity/carcinogenicity when added exogenously, but the chemistry of these reactions has been incompletely defined. We report NMR studies on the reactions of formaldehyde with canonical/modified nucleobases. The results reveal that hydroxymethyl hemiaminals on endocyclic nitrogens, as observed with thymidine and uridine monophosphates, are faster to form than equivalent hemiaminals on exocyclic nitrogens; however, the exocyclic adducts, as formed with adenine, guanine and cytosine, are more stable in solution...
May 16, 2018: Organic & Biomolecular Chemistry
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