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https://www.readbyqxmd.com/read/28222577/acute-ingestion-of-neuromuscular-enhancement-supplements-do-not-improve-power-output-work-capacity-and-cognition
#1
Jennifer A Bunn, Andrew Crossley, Morgan D Timiney
BACKGROUND: Improving motor unit recruitment and function is trainable and positively affects performance. Evidence suggests that supplementation of choline, uridine, and docosahexaenoic acid (DHA) may also enhance neuromuscular function. The purpose of this study was to assess the influence of acute ingestion of these supplements on anaerobic exercise performance and cognition. METHODS: Twenty college-aged trained males (21.2 ± 1.4 years, 181.2 ± 6.1 cm, 94.4 ± 20...
February 21, 2017: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/28222188/the-thermodynamics-of-pr55gag-rna-interaction-regulate-the-assembly-of-hiv
#2
Hanumant S Tanwar, Keith K Khoo, Megan Garvey, Lynne Waddington, Andrew Leis, Marcel Hijnen, Tony Velkov, Geoff J Dumsday, William J McKinstry, Johnson Mak
The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced by the oligomerization of Pr55Gag...
February 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28221022/quantitative-13c-traces-of-glucose-fate-in-hepatitis-b-virus-infected-hepatocytes
#3
Qianfen Wan, Yulan Wang, Huiru Tang
Quantitative characterization of 13C-labeled metabolites is an important part of the stable isotope tracing method widely used in metabolic flux analysis. Due to long relaxation time and low sensitivity of 13C nuclei, direct measurement of 13C labeled metabolites using one dimensional 13C NMR often fails to meet the demand of metabolomics studies especially with large number of samples and metabolites having low abundance. Although HSQC-based 2D NMR methods have improved sensitivity with inversion detection, they are time-consuming thus unsuitable for high-throughput absolute quantification of 13C-labeled metabolites...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28218716/sulfur-modifications-of-the-wobble-u34-in-trnas-and-their-intracellular-localization-in-eukaryotic-cells
#4
REVIEW
Yumi Nakai, Masato Nakai, Takato Yano
The wobble uridine (U34) of transfer RNAs (tRNAs) for two-box codon recognition, i.e., tRNA(Lys)UUU, tRNA(Glu)UUC, and tRNA(Gln)UUG, harbor a sulfur- (thio-) and a methyl-derivative structure at the second and fifth positions of U34, respectively. Both modifications are necessary to construct the proper anticodon loop structure and to enable them to exert their functions in translation. Thio-modification of U34 (s²U34) is found in both cytosolic tRNAs (cy-tRNAs) and mitochondrial tRNAs (mt-tRNAs). Although l-cysteine desulfurase is required in both cases, subsequent sulfur transfer pathways to cy-tRNAs and mt-tRNAs are different due to their distinct intracellular locations...
February 18, 2017: Biomolecules
https://www.readbyqxmd.com/read/28205048/mild-orotic-aciduria-in-umps-heterozygotes-a-metabolic-finding-without-clinical-consequences
#5
Saskia B Wortmann, Margaret A Chen, Roberto Colombo, Alessandro Pontoglio, Bader Alhaddad, Lorenzo D Botto, Tatiana Yuzyuk, Curtis R Coughlin, Maria Descartes, Stephanie Grűnewald, Bruno Maranda, Philippa B Mills, James Pitt, Catherine Potente, Richard Rodenburg, Leo A J Kluijtmans, Srirangan Sampath, Emil F Pai, Ron A Wevers, George E Tiller
BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life...
February 15, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28199831/inhibition-of-p2y6-signaling-in-agrp-neurons-reduces-food-intake-and-improves-systemic-insulin-sensitivity-in-obesity
#6
Sophie Marie Steculorum, Katharina Timper, Linda Engström Ruud, Nadine Evers, Lars Paeger, Stephan Bremser, Peter Kloppenburg, Jens Claus Brüning
Uridine-diphosphate (UDP) and its receptor P2Y6 have recently been identified as regulators of AgRP neurons. UDP promotes feeding via activation of P2Y6 receptors on AgRP neurons, and hypothalamic UDP concentrations are increased in obesity. However, it remained unresolved whether inhibition of P2Y6 signaling pharmacologically, globally, or restricted to AgRP neurons can improve obesity-associated metabolic dysfunctions. Here, we demonstrate that central injection of UDP acutely promotes feeding in diet-induced obese mice and that acute pharmacological blocking of CNS P2Y6 receptors reduces food intake...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28187683/proteomics-profiling-of-chimeric-truncated-tissue-plasminogen-activator-producing-chinese-hamster-ovary-cells-cultivated-in-a-chemically-defined-medium-supplemented-with-protein-hydrolysates
#7
Bahareh Azarian, Seyedeh Matin Sajedin, Amin Azimi, Mozhgan Raigani, Behrouz Vaziri, Fatemeh Davami
Background: Culture media enrichment through the addition of protein hydrolysates is beneficial for achieving higher protein expression. Methods: In this study, designing the optimum mixture of four soy and casein-derived hydrolysates was successfully performed by design of experiment and specific productivity increased in all predicted combinations. Protein profile of recombinant CHO (rCHO) cells producing tissue plasminogen activator in a serum-free medium (SFM) supplemented with designed hydrolysate additives was compared to that of rCHO cells cultivated in SFM...
11, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28181004/mass-spectrometric-analysis-of-non-canonical-cyclic-nucleotides
#8
Heike Bähre, Volkhard Kaever
Contemporary investigations regarding the (patho)physiological roles of the non-canonical cyclic nucleoside monophosphates (cNMP) cytidine 3',5'-cyclic monophosphate (cCMP) and uridine 3',5'-cyclic monophosphate (cUMP) have been hampered by the lack of highly specific and sensitive analytic methods for these analytes. In addition, the existence of 2',3'-cNMP besides 3',5'-cNMP has been described recently. HPLC coupled with tandem mass spectrometry (HPLC-MS/MS) is the method of choice for identification and quantification of low-molecular weight endogenous metabolites...
February 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28169522/entropy-and-enzyme-catalysis
#9
Johan Åqvist, Masoud Kazemi, Geir Villy Isaksen, Bjørn Olav Brandsdal
The role played by entropy for the enormous rate enhancement achieved by enzymes has been debated for many decades. There are, for example, several confirmed cases where the activation free energy is reduced by around 10 kcal/mol due to entropic effects, corresponding to a rate enhancement of ∼10(7) compared to the uncatalyzed reaction. However, despite substantial efforts from both the experimental and theoretical side, no real consensus has been reached regarding the origin of such large entropic contributions to enzyme catalysis...
February 7, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28163244/colonic-transcriptional-response-to-1%C3%AE-25-oh-2-vitamin-d3-in-african-and-european-americans
#10
Dereck Alleyne, David B Witonsky, Brandon Mapes, Shigeki Nakagome, Meredith Sommars, Ellie Hong, Katy A Muckala, Anna Di Rienzo, Sonia S Kupfer
Colorectal cancer (CRC) is a significant health burden especially among African Americans (AA). Epidemiological studies have correlated low serum vitamin D with CRC risk, and, while hypovitaminosis D is more common and more severe in AA, the mechanisms by which vitamin D modulates CRC risk and how these differ by race are not well understood. Active vitamin D (1α,25(OH)2D3) has chemoprotective effects primarily through transcriptional regulation of target genes in the colon. We hypothesized that transcriptional response to 1α,25(OH)2D3 differs between AA and European Americans (EA) irrespective of serum vitamin D and that regulatory variants could impact transcriptional response...
February 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28160163/nucleotide-selectivity-in-abiotic-rna-polymerization-reactions
#11
Kristin M Coari, Rebecca C Martin, Kopal Jain, Linda B McGown
In order to establish an RNA world on early Earth, the nucleotides must form polymers through chemical rather than biochemical reactions. The polymerization products must be long enough to perform catalytic functions, including self-replication, and to preserve genetic information. These functions depend not only on the length of the polymers, but also on their sequences. To date, studies of abiotic RNA polymerization generally have focused on routes to polymerization of a single nucleotide and lengths of the homopolymer products...
February 3, 2017: Origins of Life and Evolution of the Biosphere
https://www.readbyqxmd.com/read/28146050/uridine-triphosphate-thio-analogues-inhibit-platelet-p2y12-receptor-and-aggregation
#12
Dursun Gündüz, Christian Tanislav, Daniel Sedding, Mariana Parahuleva, Sentot Santoso, Christian Troidl, Christian W Hamm, Muhammad Aslam
Platelet P2Y12 is an important adenosine diphosphate (ADP) receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma, we demonstrate that UTP inhibits P2Y12 but not P2Y₁ receptors and antagonises 10 µM ADP-induced platelet aggregation in a concentration-dependent manner with an IC50 value of ~250 °µM...
January 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28143982/differential-binding-of-mitochondrial-transcripts-by-mrb8170-and-mrb4160-regulates-distinct-editing-fates-of-mitochondrial-mrna-in-trypanosomes
#13
Sameer Dixit, Michaela Müller-McNicoll, Vojtěch David, Kathi Zarnack, Jernej Ule, Hassan Hashimi, Julius Lukeš
: A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28134782/role-of-pseudouridine-formation-by-deg1-for-functionality-of-two-glutamine-isoacceptor-trnas
#14
Roland Klassen, Raffael Schaffrath
Loss of Deg1/Pus3 and concomitant elimination of pseudouridine in tRNA at positions 38 and 39 (ψ38/39) was shown to specifically impair the function of tRNA(Gln)UUG under conditions of temperature-induced down-regulation of wobble uridine thiolation in budding yeast and is linked to intellectual disability in humans. To further characterize the differential importance of the frequent ψ38/39 modification for tRNAs in yeast, we analyzed the in vivo function of non-sense suppressor tRNAs SUP4 and sup70-65 in the absence of the modifier...
January 26, 2017: Biomolecules
https://www.readbyqxmd.com/read/28130882/direct-intracellular-delivery-of-cell-impermeable-probes-of-protein-glycosylation-using-nanostraws
#15
Alexander Minyi Xu, Derek Schawn Wang, Peyton Shieh, Yuhong Cao, Nick Melosh
Bioorthogonal chemistry is an effective tool for measuring metabolic pathways and cellular activity, yet its use is currently limited due to the difficulty of introducing probes past the cell membrane and into the cytoplasm, especially as more complex probes are desired. Here we present a simple and minimally perturbative technique to deliver functional probes of glycolysylation into cells using a nanostructured "nanostraw" delivery system. Nanostraws provide large scale intracellular access to cells through fluidic conduits that remain small enough to minimize cell perturbation...
January 28, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28130447/pseudouridine-modification-inhibits-muscleblind-like-1-mbnl1-binding-to-ccug-repeats-and-minimally-structured-rna-through-reduced-rna-flexibility
#16
Elaine deLorimier, Melissa N Hinman, Jeremy Copperman, Kausiki Datta, Marina Guenza, J Andrew Berglund
Myotonic dystrophy type 2 is a genetic neuromuscular disease caused by the expression of expanded CCUG-repeat RNAs from the non-coding region of the CCHC-Type Zinc Finger Nucleic Acid Binding Protein (CNBP) gene. These CCUG repeats bind and sequester a family of RNA binding proteins known as Muscleblind-like 1, 2, and 3 (MBNL1, MBNL2, and MBNL3), and sequestration plays a significant role in pathogenicity. MBNL proteins are alternative splicing regulators that bind to the consensus RNA sequence YGCY (Y = pyrimidine)...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28130366/analysis-of-uracil-phosphoribosyltransferase-expression-in-mycobacterium-tuberculosis-and-evaluation-of-upp-knockout-strain-in-infected-mice
#17
Anne Drumond Villela, Ha Pham, Victoria Jones, Anna E Grzegorzewicz, Valnês da Silva Rodrigues-Junior, Maria Martha Campos, Luiz Augusto Basso, Mary Jackson, Diógenes Santiago Santos
The upp (Rv3309c)-encoded uracil phosphoribosyltransferase from Mycobacterium tuberculosis (MtUPRT) converts uracil and 5-phosphoribosyl-α-1-pyrophosphate into pyrophosphate and uridine 5'-monophosphate, the precursor of all pyrimidine nucleotides. A M. tuberculosis knockout strain for upp gene was generated by allelic replacement. Knockout and complemented strains were validated by a functional assay of uracil incorporation. A basal level of MtUPRT expression is shown to be independent of either growth medium used, addition of bases, or oxygen presence/absence...
January 26, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28129885/renoprotective-chemical-constituents-from-an-edible-mushroom-pleurotus-cornucopiae-in-cisplatin-induced-nephrotoxicity
#18
Seoung Rak Lee, Dahae Lee, Hae-Jeung Lee, Hyung Jun Noh, Kiwon Jung, Ki Sung Kang, Ki Hyun Kim
Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12)...
January 19, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28129265/parenteral-and-enteral-nutrition-in-surgical-critical-care-plasma-metabolomics-demonstrates-divergent-effects-on-nitrogen-fatty-acid-ribonucleotide-and-oxidative-metabolism
#19
Brodie A Parent, Max Seaton, Danijel Djukovic, Haiwei Gu, Brittany Wheelock, Daniel Raftery, Grant E O'Keefe
BACKGROUND: Artificial nutrition support is central to the care of critically ill patients and is primarily provided enterally (EN). There are circumstances when parenteral nutrition (PN) is considered necessary. We are uncertain how each of these approaches confer clinical benefits beyond simply providing calories. We sought to better understand how each of these techniques influence metabolism in critically-ill patients using a broad-based metabolomics approach. Metabolic responses to EN and PN may differ in ways that could help us understand how to optimize use of these therapies...
January 26, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28128958/chemoenzymatic-synthesis-of-4-fluoro-n-acetylhexosamine-uridine-diphosphate-donors-chain-terminators-in-glycosaminoglycan-synthesis
#20
Victor L Schultz, Xing Zhang, Kathryn Linkens, Jenna Rimel, Dixy E Green, Paul L DeAngelis, Robert J Linhardt
Unnatural uridine diphosphate (UDP)-sugar donors, UDP-4-deoxy-4-fluoro-N-acetylglucosamine (4FGlcNAc) and UDP-4-deoxy-4-fluoro-N-acetylgalactosamine (4FGalNAc), were prepared using both chemical and chemoenzymatic syntheses relying on N-acetylglucosamine-1-phosphate uridylyltransferase (GlmU). The resulting unnatural UDP-sugar donors were then tested as substrates in glycosaminoglycan synthesis catalyzed by various synthases. UDP-4FGlcNAc was transferred onto an acceptor by Pastuerella multocida heparosan synthase 1 and subsequently served as a chain terminator...
February 6, 2017: Journal of Organic Chemistry
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