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https://www.readbyqxmd.com/read/27914071/differential-radial-capillary-action-of-ligand-assay-dracala-for-high-throughput-detection-of-protein-metabolite-interactions-in-bacteria
#1
Mona W Orr, Vincent T Lee
Bacteria rely on numerous nucleotide second messengers for signal transduction such as cyclic AMP, cyclic-di-GMP, and cyclic-di-AMP. Although a number of receptors responsible for known regulated phenotypes have been established, the completeness of protein receptors in any given organism remains elusive. We have developed a method called differential radial capillary action of ligand assay (DRaCALA) that allows for an unbiased, systematic high-throughput screen for the detection of ligand binding proteins encoded by a genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27911438/evolutionary-convergence-in-experimental-pseudomonas-populations
#2
Peter A Lind, Andrew D Farr, Paul B Rainey
Model microbial systems provide opportunity to understand the genetic bases of ecological traits, their evolution, regulation and fitness contributions. Experimental populations of Pseudomonas fluorescens rapidly diverge in spatially structured microcosms producing a range of surface-colonising forms. Despite divergent molecular routes, wrinkly spreader (WS) niche specialist types overproduce a cellulosic polymer allowing mat formation at the air-liquid interface and access to oxygen. Given the range of ways by which cells can form mats, such phenotypic parallelism is unexpected...
December 2, 2016: ISME Journal
https://www.readbyqxmd.com/read/27904874/imaging-of-accidental-contamination-by-fluorine-18-solution-a-quick-troubleshooting-procedure
#3
Kalevi Kairemo, Aki Kangasmäki
To the best of our knowledge, imaging of accidental exposure to radioactive fluorine-18 (F-18) due to liquid spill has not been described earlier in the scientific literature. The short half-life of F-18 (t½=110 min), current radiation safety requirements, and Good Manufacturing Practice (GMP) regulations on radiopharmaceuticals have restrained the occurrence of these incidents. The possibility of investigating this type of incidents by gamma and positron imaging is also quite limited. Additionally, a quick and precise analysis of radiochemical contamination is cumbersome and sometimes challenging if the spills of radioactive materials are low in activity...
2016: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#4
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902332/inhibition-of-hepatitis-b-virus-replication-by-activation-of-the-cgas-sting-pathway
#5
Jing He, Ruidong Hao, Dan Liu, Xing Liu, Shaoshuai Wu, Shuting Guo, Yuan Wang, Deyin Guo
Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyzes synthesis of the second messenger cGAMP, which activates the downstream signaling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, we showed that the replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP...
October 31, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900812/spontaneous-assembly-of-an-organic-inorganic-nucleic-acid-z-dna-double-helix-structure
#6
Vladislav Kulikov, Naomi A B Johnson, Andrew J Surman, Marie Hutin, Sharon M Kelly, Mohammed Hezwani, De-Liang Long, Gerd Meyer, Leroy Cronin
Herein, we report a hybrid polyoxometalate organic-inorganic compound, Na2 [(HGMP)2 Mo5 O15 ]⋅7 H2 O (1; where GMP=guanosine monophosphate), which spontaneously assembles into a structure with dimensions that are strikingly similar to those of the naturally occurring left-handed Z-form of DNA. The helical parameters in the crystal structure of the new compound, such as rise per turn and helical twist per dimer, are nearly identical to this DNA conformation, allowing a close comparison of the two structures...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27899451/real-time-spatial-and-temporal-mapping-of-the-distribution-of-c-di-gmp-during-biofilm-development
#7
Harikrishnan A S Nair, Saravanan Periasamy, Yang Liang, Staffan Kjelleberg, Scott A Rice
Bis-(3 ́-5 ́)-cyclic dimeric guanosine monophosphate (c-di-GMP) is a dynamic intracellular signaling molecule that plays a central role in the biofilm life cycle. Current methodologies for the quantification of c-di-GMP are typically based on chemical extraction, representing end-point measurements. Chemical methodologies also fail to take into consideration the physiological heterogeneity of the biofilm and thus represents an average c-di-GMP concentration across the entire biofilm. To address these problems, a ratiometric, image-based quantification method has been developed based on expression of the green fluorescence protein (GFP) under the control of the c-di-GMP responsive cdrA promoter (1)...
November 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27897378/subcellular-clustering-of-a-putative-c-di-gmp-dependent-exopolysaccharide-machinery-affecting-macro-colony-architecture-in-bacillus-subtilis
#8
Patricia Bedrunka, Peter L Graumann
The structure of bacterial biofilms is predominantly established through the secretion of extracellular polymeric substances (EPS). We show that Bacillus subtilis contains an operon (ydaJ-N) whose induction leads to increased Congo Red staining of biofilms and strongly altered biofilm architecture, suggesting that it mediates the production of an unknown exopolysaccharide. Supporting this idea, overproduction of YdaJKLMN leads to cell clumping during exponential growth in liquid culture, and also causes colony morphology alterations in wild type cells, as well as in a mutant background lacking the major exopolysaccharide of B...
November 29, 2016: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/27895975/anti-helicobacter-pylori-effect-of-cag-nana-a-new-sialic-acid-derivative
#9
Yun-Hee Rhee, Hyun-Jeong Ku, Hye-Ji Noh, Hyang-Hyun Cho, Hee-Kyong Kim, Jin-Chul Ahn
AIM: To investigate the bactericidal effects of calcium chelated N-acetylneuraminic acid-glycomacropeptide (CaG-NANA) against Helicobacter pylori (H. pylori). METHODS: For manufacture of CaG-NANA, calcium (Ca) was combined with glycomacropeptide (GMP) by chelating, and N-acetylneuraminic acid (NANA) was produced with Ca-GMP substrate by an enzymatic method. The final concentration of each component was 5% Ca, 7% NANA, 85% GMP, and 3% water. For in vitro study, various concentrations of CaG-NANA were investigated under the minimal inhibitory concentration (MIC)...
November 15, 2016: World Journal of Gastrointestinal Pathophysiology
https://www.readbyqxmd.com/read/27893989/drug-discovery-targeting-heme-based-sensors-and-their-coupled-activities
#10
Eduardo Henrique Silva Sousa, Luiz Gonzaga de França Lopes, Gonzalo Gonzalez, Marie-Alda Gilles-Gonzalez
Heme-based sensors have emerged during the last 20years as being a large family of proteins that occur in all kingdoms of life. A myriad of biological adaptations are associated with these sensors, which include vasodilation, bacterial virulence, dormancy, chemotaxis, biofilm formation, among others. Due to the key activities regulated by these proteins along with many other systems that use similar output domains, there is a growing interest in developing small molecules as their regulators. Here, we review the development of potential activators and inhibitors for many of these systems, including human soluble guanylate cyclase, c-di-GMP-related enzymes, Mycobacterium tuberculosis DevR/DevS/DosT (differentially expressed in virulent strain response regulator/sensor/dormancysurvival sensorT), the Rev-erb-α and β nuclear receptor, among others...
November 20, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27886076/pathogens-inactivated-by-low-energy-electron-irradiation-maintain-antigenic-properties-and-induce-protective-immune-responses
#11
Jasmin Fertey, Lea Bayer, Thomas Grunwald, Alexandra Pohl, Jana Beckmann, Gaby Gotzmann, Javier Portillo Casado, Jessy Schönfelder, Frank-Holm Rögner, Christiane Wetzel, Martin Thoma, Susanne M Bailer, Ekkehard Hiller, Steffen Rupp, Sebastian Ulbert
Inactivated vaccines are commonly produced by incubating pathogens with chemicals such as formaldehyde or β-propiolactone. This is a time-consuming process, the inactivation efficiency displays high variability and extensive downstream procedures are often required. Moreover, application of chemicals alters the antigenic components of the viruses or bacteria, resulting in reduced antibody specificity and therefore stimulation of a less effective immune response. An alternative method for inactivation of pathogens is ionizing radiation...
November 23, 2016: Viruses
https://www.readbyqxmd.com/read/27881736/reactive-oxygen-species-drive-evolution-of-pro-biofilm-variants-in-pathogens-by-modulating-cyclic-di-gmp-levels
#12
Song Lin Chua, Yichen Ding, Yang Liu, Zhao Cai, Jianuan Zhou, Sanjay Swarup, Daniela I Drautz-Moses, Stephan Christoph Schuster, Staffan Kjelleberg, Michael Givskov, Liang Yang
The host immune system offers a hostile environment with antimicrobials and reactive oxygen species (ROS) that are detrimental to bacterial pathogens, forcing them to adapt and evolve for survival. However, the contribution of oxidative stress to pathogen evolution remains elusive. Using an experimental evolution strategy, we show that exposure of the opportunistic pathogen Pseudomonas aeruginosa to sub-lethal hydrogen peroxide (H2O2) levels over 120 generations led to the emergence of pro-biofilm rough small colony variants (RSCVs), which could be abrogated by l-glutathione antioxidants...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27879319/amp-activated-kinase-ampk-promotes-innate-immunity-and-antiviral-defense-through-modulation-of-stimulator-of-interferon-genes-sting-signaling
#13
Daniel Prantner, Darren J Perkins, Stefanie N Vogel
The host protein Stimulator of Interferon Genes (STING) has been shown to be essential for recognition of both viral and intracellular bacterial pathogens, but its regulation remains unclear. Previously, we reported that mitochondrial membrane potential regulates STING-dependent IFN-beta induction independently of ATP synthesis. Since mitochondrial membrane potential controls calcium homeostasis, and AMP-activated protein kinase (AMPK) is regulated, in part, by intracellular calcium, we postulated that AMPK participates in STING activation; however, its role has yet to be been defined...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27873282/ebv-directed-t-cell-therapeutics-for-ebv-associated-lymphomas
#14
Lauren P McLaughlin, Stephen Gottschalk, Cliona M Rooney, Catherine M Bollard
Epstein Barr virus (EBV) is a human gamma herpes virus that establishes latency in B cells after primary infection. EBV generally only causes a mild, self-limiting viral illness but is also associated with several malignancies including posttransplantation lymphoproliferative disorder in the immunosuppressed host as well as Hodgkin and non-Hodgkin lymphoma in the immune competent host. The expression of EBV antigens by lymphoma has important applications as targets for adoptive T cell therapy. However, as many lymphomas only express subdominant EBV antigens that are less immunogenic, novel strategies are needed to manufacture EBV-specific T cell products specific for Latent Membrane Protein 1 (LMP1) and LMP2, which are expressed in lymphomas with type II and III latency...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27871960/useful-implications-of-low-dose-long-term-use-of-pde-5-inhibitors
#15
REVIEW
Taymour Mostafa
INTRODUCTION: Phosphodiesterase type 5 (PDE-5) hydrolyzes cyclic guanylate monophosphate (cGMP) specifically to 5' GMP, promoting successful corporeal vascular relaxation and penile erection during sexual stimulation. Oral PDE-5 inhibitors such as sildenafil, vardenafil, tadalafil, and avanafil have provided noninvasive, effective, well-tolerated treatment for erectile dysfunction (ED) patients and, at the same time, stimulated both academic and clinical interests. Lately, some oral PDE-5 inhibitors were released as low-dose preparations with the concept of potential daily administration and long-term use...
July 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27871906/adenosine-but-not-guanosine-protects-vaginal-epithelial-cells-from-trichomonas-vaginalis-cytotoxicity
#16
Camila Braz Menezes, Amanda Piccoli Frasson, Lucia Collares Meirelles, Tiana Tasca
Trichomonas vaginalis causes the most common non-viral sexually transmitted disease worldwide. The cytoadherence and cytotoxicity upon the vaginal epithelial cells are crucial for the infection. Extracellular nucleotides are released during cell damage and, along with their nucleosides, can activate purinoceptors. The opposing effects of nucleotides versus nucleosides are regulated by ectonucleotidases. Herein we evaluated the hemolysis and cytolysis induced by T. vaginalis, as well as the extracellular nucleotide hydrolysis along with the effects mediated by nucleotides and nucleosides on cytotoxicity...
November 18, 2016: Microbes and Infection
https://www.readbyqxmd.com/read/27863906/post-translational-control-of-intracellular-pathogen-sensing-pathways
#17
REVIEW
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
November 15, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27863149/cgas-expression-in-patients-with-systemic-lupus-erythematosus
#18
Jie An, Laura Durcan, Reynold M Karr, Tracy A Briggs, Gillian I Rice, Thomas H Teal, Joshua J Woodward, Keith B Elkon
OBJECTIVES Type I interferon (IFN-I) is implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) and 'interferonopathies' such as Aicardi-Goutieres Syndrome. A recently discovered DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS) is linked to AGS and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to IFN-I production in SLE patients. METHODS SLE disease activity was measured by SELENA-SLEDAI. cGAS and interferon stimulated gene (ISG) mRNA expression was quantified by quantitative PCR ...
November 18, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27860834/regulation-of-mammalian-oocyte-meiosis-by-intercellular-communication-within-the-ovarian-follicle
#19
Laurinda Jaffe, Jeremy R Egbert
Meiotic progression in mammalian preovulatory follicles is controlled by the granulosa cells around the oocyte. Cyclic GMP (cGMP) generated in the granulosa cells diffuses through gap junctions into the oocyte, maintaining meiotic prophase arrest. Luteinizing hormone then acts on receptors in outer granulosa cells to rapidly decrease cGMP. This occurs by two complementary pathways: cGMP production is decreased by dephosphorylation and inactivation of the NPR2 guanylyl cyclase, and cGMP hydrolysis is increased by activation of the PDE5 phosphodiesterase...
November 14, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27857051/elevation-of-the-acth-cortisol-ratio-in-female-opioid-dependent-patients-a-biomarker-of-aging-and-correlate-of-metabolic-and-immune-activation
#20
(no author information available yet)
BACKGROUND: Whilst the hypothalamic-pituitary-adrenal (HPA) Axis is a major stress axis, and is necessarily perturbed in opioid dependency, and stress is a major contributor to aging mechanisms, the HPA axis has not been studied in opioid dependency in an age-dependent manner. OBJECTIVE: Hypothesis - Differences in age dependent levels of HPA components. DESIGN: Cross-sectional comparison of general medical and opioid dependent patients (ODP, GMP)...
September 18, 2016: Neuro Endocrinology Letters
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