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https://www.readbyqxmd.com/read/29334455/modulating-the-molybdenum-coordination-sphere-of-escherichia-coli-trimethylamine-n-oxide-reductase
#1
Paul Kaufmann, Benjamin R Duffus, Biljana Mitrova, Chantal Iobbi-Nivol, Christian Teutloff, Manfred Nimtz, Lothar Jänsch, Ulla Wollenberger, Silke Leimkühler
The well-studied enterobacterium Escherichia coli present in the human gut is able to reduce TMAO to trimethylamine (TMA) during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme belonging to the dimethylsulfoxide (DMSO) reductase family of molybdoenzymes. We report on a system for the in vitro reconstitution of TorA with molybdenum cofactors (Moco) from different sources. Higher TMAO reductase activities for TorA were obtained when using Moco-sources containing a sulfido ligand at the molybdenum atom...
January 15, 2018: Biochemistry
https://www.readbyqxmd.com/read/29332336/downregulation-of-guanine-nucleotide-binding-protein-beta-1-gnb1-is-associated-with-worsened-prognosis-of-clearcell-renal-cell-carcinoma-and-is-related-to-vegf-signaling-pathway
#2
C Chen, H Chi, L Min, Z Junhua
PURPOSE: Clear-cell renal cell carcinoma (ccRCC) is characterized by genetic abnormalities, while the role of Guanine Nucleotide-Binding Protein Beta 1 (GNB1) in ccRCC has not been studied. We thus aimed to evaluate the expression and prognostic value of GNB1 in ccRCC. METHODS: A two-stage study (exploration and validation) was conducted using in silico and immunohistochemical (IHC) scoring of ccRCC samples from our institute, to evaluate the association between GNB1 expression and clinicopathological parameters of ccRCC patients...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330301/genetic-control-of-predominantly-error-free-replication-through-an-acrolein-derived-minor-groove-dna-adduct
#3
Jung-Hoon Yoon, Richard P Hodge, Linda C Hackfeld, Jeseong Park, Jayati Roy Choudhury, Satya Prakash, Louise Prakash
Acrolein, an α, β unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from metabolic oxidation of polyamines, and it is an ubiquitous environmental pollutant. The reaction of acrolein with the N2 of guanine in DNA leads to the formation of γ-hydroxy-1-N2-propano-2' deoxyguanosine (γ-HOPdG) which can exist in DNA in a ring-closed or a ring-opened form. Here we identify the translesion synthesis (TLS) DNA polymerases (Pols) which conduct replication through the permanently ring-opened reduced form of γ-HOPdG [(r) γ-HOPdG] and show that replication through this adduct is mediated via Rev1/Polη, Polι/Polκ, and Polθ dependent pathways, respectively...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29329083/a-label-free-electrochemical-system-for-comprehensive-monitoring-of-o-chlorophenol
#4
Xiaolin Zhu, Kexin Zhang, Nan Lu, Yangyang Yu, Xing Yuan, Jiunian Guan
o-Chlorophenol (OCP) is a priority pollutant that poses serious health threats to the public. The following study designs a simple electrochemical system to monitor the concentration and toxicity of OCP. This system was primarily characterized by the integration of both physicochemical and biological monitoring procedures that had a synergistic effect between the functionalized carbon nanotubes and rhodamine B. This resulted in excellent electrocatalytic activities toward OCP and cellular purine bases. The peak current of OCP was linear with concentrations ranging from 0...
January 4, 2018: Chemosphere
https://www.readbyqxmd.com/read/29327208/analysis-of-dna-modifications-in-aging-research
#5
REVIEW
Dustin R Masser, Niran Hadad, Hunter Porter, Michael B Stout, Archana Unnikrishnan, David R Stanford, Willard M Freeman
As geroscience research extends into the role of epigenetics in aging and age-related disease, researchers are being confronted with unfamiliar molecular techniques and data analysis methods that can be difficult to integrate into their work. In this review, we focus on the analysis of DNA modifications, namely cytosine methylation and hydroxymethylation, through next-generation sequencing methods. While older techniques for modification analysis performed relative quantitation across regions of the genome or examined average genome levels, these analyses lack the desired specificity, rigor, and genomic coverage to firmly establish the nature of genomic methylation patterns and their response to aging...
January 11, 2018: GeroScience
https://www.readbyqxmd.com/read/29326313/dna-methylation-and-age-independent-cardiovascular-risk-an-epigenome-wide-approach-the-regicor-registre-giron%C3%A3-del-cor-study
#6
Alba Fernández-Sanlés, Sergi Sayols-Baixeras, Santiago Curcio, Isaac Subirana, Jaume Marrugat, Roberto Elosua
OBJECTIVE: The objectives of this study were to decipher whether age-independent cardiovascular risk is associated with DNA methylation at 5'-cytosine-phosphate-guanine-3' (CpG) level and to determine whether these differential methylation signatures are associated with the incidence of cardiovascular events. APPROACH AND RESULTS: We designed a 2-stage, cross-sectional, epigenome-wide association study. Age-independent cardiovascular risk calculation was based on vascular age and on the residuals of the relationship between age and cardiovascular risk...
January 11, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29325019/deep-molecular-phenotypes-link-complex-disorders-and-physiological-insult-to-cpg-methylation
#7
Shaza B Zaghlool, Dennis O Mook-Kanamori, Sara Kader, Nisha Stephan, Anna Halama, Rudolf Engelke, Hina Sarwath, Eman K Al-Dous, Yasmin A Mohamoud, Werner Roemisch-Margl, Jerzy Adamski, Gabi Kastenmüller, Nele Friedrich, Alessia Visconti, Pei-Chien Tsai, Tim Spector, Jordana Bell, Mario Falchi, Annika Wahl, Melanie Waldenberger, Annette Peters, Christian Gieger, Maija Pezer, Gordan Lauc, Johannes Graumann, Joel A Malek, Karsten Suhre
Epigenetic regulation of cellular function provides a mechanism for rapid organismal adaptation to changes in health, lifestyle, and environment. Associations of cytosine-guanine di-nucleotide (CpG) methylation with clinical endpoints that overlap with metabolic phenotypes suggest a regulatory role for these CpG sites in the body's response to disease or environmental stress. We previously identified 20 CpG sites in an epigenome-wide association study (EWAS) with metabolomics that were also associated in recent EWASs with diabetes-, obesity-, and smoking-related endpoints...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29322767/ph-dependent-switching-of-base-pairs-using-artificial-nucleobases-with-carboxyl-groups
#8
Tanasak Kaewsomboon, Shuhei Nishizawa, Takashi Kanamori, Hideya Yuasa, Akihiro Ohkubo
In this study we report synthesis of modified oligonucleotides consisting of benzoic acid or isophthalic acid residues as new nucleobases. As evaluated by UV thermal denaturation analysis at different pH conditions (5.0, 6.0, 7.0, and 8.0), these modified oligonucleotides exhibited pH-dependent recognition of natural nucleobases and one is first found to be capable of base pair switching in response to a pH change. The isophthalic acid residue incorporated into the oligonucleotide on a D-threoninol backbone could preferentially bind with adenine but with guanine in response to a change in the pH conditions from pH 5 to pH 7 (or 8) without significant difference in duplex stability...
January 11, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29321251/control-of-septin-filament-flexibility-and-bundling-by-subunit-composition-and-nucleotide-interactions
#9
Anum Khan, Jay Newby, Amy S Gladfelter
Septins self-assemble into heteromeric rods and filaments to act as scaffolds and modulate membrane properties. How cells tune the biophysical properties of septin filaments to control filament flexibility and length, and in turn the size, shape, and position of higher-order septin structures is not well understood. We examined how rod composition and nucleotide availability influence physical properties of septins such as annealing, fragmentation, bundling and bending. We found that septin complexes have symmetric termini, even when both Shs1 and Cdc11 are coexpressed...
January 10, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29321250/myosin-ii-interacting-guanine-nucleotide-exchange-factor-myogef-promotes-bleb-retraction-via-stimulating-cortex-reassembly-at-the-bleb-membrane
#10
Meng Jiao, Di Wu, Qize Wei
Blebs are involved in various biological processes such as cell migration, cytokinesis, and apoptosis. While the expansion of blebs is largely an intracellular pressure-driven process, the retraction of blebs is believed to be driven by RhoA activation that leads to the reassembly of the actomyosin cortex at the bleb membrane. However, it is still poorly understood how RhoA is activated at the bleb membrane. Here, we provide evidence demonstrating that nonmuscle myosin II-interacting guanine nucleotide exchange factor (MYOGEF) is implicated in bleb retraction via stimulating RhoA activation and the reassembly of an actomyosin network at the bleb membrane during bleb retraction...
January 10, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29321004/rcc2-over-expression-in-tumor-cells-alters-apoptosis-and-drug-sensitivity-by-regulating-rac1-activation
#11
Nan Wu, Dong Ren, Su Li, Wenli Ma, Shaoyan Hu, Yan Jin, Sheng Xiao
BACKGROUND: Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. METHODS: Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs...
January 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29320630/structural-insight-into-the-discrimination-between-8-oxoguanine-glycosidic-conformers-by-dna-repair-enzymes-a-molecular-dynamics-study-of-hogg1-and-fpg
#12
Shahin Sowlati-Hashjin, Stacey D Wetmore
hOgg1 and FPG are the primary DNA repair enzymes responsible for removing the major guanine oxidative product (G), namely 7,8-dihydro-8-oxoguanine (OG), in humans and bacteria, respectively. While natural G adopts the anti conformation and forms a Watson-Crick pair with cytosine (C), OG can also adopt the syn conformation and form a Hoogsteen pair with adenine (A). hOgg1 removes OG paired with C, but is inactive toward the OG:A pair. In contrast, FPG removes OG from OG:C pairs, and also exhibits appreciable (although diminished) activity toward OG:A pairs...
January 10, 2018: Biochemistry
https://www.readbyqxmd.com/read/29318657/crystal-structure-of-tetrameric-human-rabin8-gef-domain
#13
Melanie Vetter, Niels Boegholm, Anni Christensen, Sagar Bhogaraju, Marie B Andersen, Anna Lorentzen, Esben Lorentzen
Rab GTPases and their effectors, activators and guanine nucleotide exchange factors (GEFs) are essential for vesicular transport. Rab8 and its GEF Rabin8 function in formation of the cilium organelle important for developmental signaling and sensory reception. Here we show by size exclusion chromatography and analytical ultracentrifugation that Rabin8 exists in equilibrium between dimers and tetramers. The crystal structure of tetrameric Rabin8 GEF domain reveals an occluded Rab8 binding site suggesting that this oligomer is enzymatically inactive, a notion we verify experimentally using Rabin8/Rab8 GEF assays...
January 10, 2018: Proteins
https://www.readbyqxmd.com/read/29317815/double-stranded-phosphodiester-cytosine-guanine-oligodeoxynucleotide-complexed-with-calcium-phosphate-as-a-potent-vaccine-adjuvant-for-activating-cellular-and-th1-type-humoral-immunities
#14
Nobutaka Hanagata, Xianglan Li, Min-Hua Chen, Jie Li, Shinya Hattori
Conventional class B cytosine-guanine (CpG) (CpG-B) oligodeoxynucleotide (ODNs) consisting of a single-stranded (ss) phosphorothioate (PT) backbone (ss CpG-B-PT) is converted from a proinflammatory cytokine inducer to a type-I interferon (IFN) inducer when complexed with cationic materials. In this study, we designed ss CpG-B and double-stranded (ds) CpG-B ODNs with a phosphodiester (PD) backbone (ss CpG-B-PD and ds CpG-B-PD, respectively) that became type-I IFN inducers upon complexation with Lipofectamine 2000 (Lipo), a cationic liposome...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29317519/%C3%AE-arrestin-biased-%C3%AE-adrenergic-signaling-promotes-extinction-learning-of-cocaine-reward-memory
#15
Bing Huang, Youxing Li, Deqin Cheng, Guanhong He, Xing Liu, Lan Ma
Extinction learning of cocaine-associated contextual cues can help prevent cocaine addicts from relapsing. Pharmacological manipulation of β-adrenergic receptor (β-AR) during extinction learning is being developed as a potential strategy to treat drug addiction. We demonstrated that the extinction learning of cocaine-associated memory was mediated by β-arrestin2-biased but not heterotrimeric guanine nucleotide-binding protein (G protein)-dependent β-adrenergic signaling. We found that administration of the nonbiased β-AR antagonist propranolol, but not the G protein-biased β-AR antagonist carvedilol, blocked extinction learning of cocaine-conditioned place preference and the associated ERK activation in the infralimbic prefrontal cortex...
January 9, 2018: Science Signaling
https://www.readbyqxmd.com/read/29317163/investigations-into-the-efficacy-of-multi-component-cocaine-vaccines
#16
Atsushi Kimishima, Margaret E Olson, Kim D Janda
Although cocaine addiction remains a serious health and societal problem in the United States, no FDA-approved treatment has been developed. Vaccines offer an exciting strategy for the treatment of cocaine addiction; however, vaccine formulations need to be optimized to improve efficacy. Herein, we examine the effectiveness of a tricomponent cocaine vaccine, defined as having its hapten (GNE) and adjuvant (cytosine-guanine oligodeoxynucleotide 1826, CpG ODN 1826) covalently linked via the immunogenic protein ovalbumin (OVA)...
December 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29316733/single-labeled-oligonucleotides-showing-fluorescence-changes-upon-hybridization-with-target-nucleic-acids
#17
REVIEW
Gil Tae Hwang
Sequence-specific detection of nucleic acids has been intensively studied in the field of molecular diagnostics. In particular, the detection and analysis of single-nucleotide polymorphisms (SNPs) is crucial for the identification of disease-causing genes and diagnosis of diseases. Sequence-specific hybridization probes, such as molecular beacons bearing the fluorophore and quencher at both ends of the stem, have been developed to enable DNA mutation detection. Interestingly, DNA mutations can be detected using fluorescently labeled oligonucleotide probes with only one fluorophore...
January 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29314494/dysregulation-of-rab5-mediated-endocytic-pathways-in-alzheimer-s-disease
#18
REVIEW
Wei Xu, Fang Fang, Jianqing Ding, Chengbiao Wu
Increasing evidence has pointed to that dysregulation of the endo-lysosomal system is an early cellular phenotype of pathogenesis for Alzheimer's disease (AD). Rab5, a small GTPase, plays a critical role in mediating these processes. Abnormal overactivation of Rab5 has been observed in post-mortem brain samples of Alzheimer's patients as well as brain samples of mouse models of AD. Recent genome-wide association studies of Alzheimer's disease have identified RIN3 (Ras and Rab Interactor 3) as a novel risk factor for the disease...
January 3, 2018: Traffic
https://www.readbyqxmd.com/read/29311059/g-quadruplex-dna-motifs-in-the-malaria-parasite-plasmodium-falciparum-and-their-potential-as-novel-antimalarial-drug-targets
#19
Lynne M Harris, Katelyn R Monsell, Florian Noulin, M Toyin Famodimu, Nicolas Smargiasso, Christian Damblon, Paul Horrocks, Catherine J Merrick
G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur in vivo in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite Plasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29310241/hsa-mir-1587-g-quadruplex-formation-and-dimerization-induced-by-nh4-molecular-crowding-environment-and-jatrorrhizine-derivatives
#20
Wei Tan, Long Yi, Zhentao Zhu, Lulu Zhang, Jiang Zhou, Gu Yuan
A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K+, Na+ and low concentration of NH4+ (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH4+ (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces...
March 1, 2018: Talanta
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