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https://www.readbyqxmd.com/read/28530267/lanthanide-based-peptide-biosensor-to-monitor-cdk4-cyclin-d-kinase-activity
#1
Juan A González-Vera, David Bouzada, Céline Bouclier, M Eugenio Vázquez, May C Morris
We describe a lanthanide biosensor that responds to CDK4 kinase activity in melanoma cell extracts through a significant and dose dependent increase in luminescence, thanks to sensitization of a DOTA[Tb(3+)] complex incorporated into a CDK4 substrate peptide by a unique tryptophan residue in an adjacent phosphoaminoacid binding moiety.
May 22, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28529635/synthesis-of-5-18-f-fluoro-%C3%AE-methyl-tryptophan-new-trp-based-pet-agents
#2
Benjamin C Giglio, Haiyang Fei, Mengzhe Wang, Hui Wang, Liu He, Huijuan Feng, Zhanhong Wu, Hongjian Lu, Zibo Li
Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (α-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of (18)F into the tryptophan aromatic ring...
2017: Theranostics
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#3
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28527020/changes-in-serum-levels-of-kynurenine-metabolites-in-paediatric-patients-affected-by-adhd
#4
Melania Evangelisti, Pietro De Rossi, Jole Rabasco, Renato Donfrancesco, Luana Lionetto, Matilde Capi, Gabriele Sani, Maurizio Simmaco, Ferdinando Nicoletti, Maria Pia Villa
This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
May 19, 2017: European Child & Adolescent Psychiatry
https://www.readbyqxmd.com/read/28526475/identification-and-preliminary-structure-activity-relationships-of-1-indanone-derivatives-as-novel-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#5
Dingding Gao, Yingxia Li
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein...
May 10, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28525989/determination-of-genetic-effects-of-atf3-and-cdkn1a-genes-on-milk-yield-and-compositions-in-chinese-holstein-population
#6
REVIEW
Bo Han, Weijun Liang, Lin Liu, Yanhua Li, Dongxiao Sun
BACKGROUND: Our previous RNA-sequencing study revealed that the ATF3 and CDKN1A genes were remarkably differentially expressed between the mammary glands of lactating Holstein cows with extremely high and low milk protein and fat percentage so that both of them were considered as candidates for milk composition. Herein, we further verified whether these genes have genetic effects on milk production traits in a Chinese Holstein cow population. RESULTS: By re-sequencing the entire coding and regulatory regions, we identified four SNPs in 5'promoter region, two in exons, seven in 3' un-translated region (UTR), and six in 3'flanking region of ATF3 gene, and one SNP in exon 5, two in 3'UTR, and two in 3'flanking region of CDKN1A gene...
May 19, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28525263/yellow-and-orange-fluorescent-proteins-with-tryptophan-based-chromophores
#7
Nina G Bozhanova, Mikhail S Baranov, Karen S Sarkisyan, Roman Gritсenko, Konstantin V Mineev, Svetlana V Golodukhina, Nadezhda S Baleeva, Konstantin A Lukyanov, Alexander S Mishin
Rapid development of new microscopy techniques exposed the need for genetically encoded fluorescent tags with special properties. Recent works demonstrated the potential of fluorescent proteins with tryptophan-based chromophores. We applied rational design and random mutagenesis to the monomeric red fluorescent protein FusionRed and found two groups of mutants carrying tryptophan-based chromophore: with yellow (535 nm) or orange (565 nm) emission. On the basis of the properties of proteins, a model synthetic chromophore, and a computational modelling we concluded that the presence of a ketone-containing chromophore in different isomeric forms can explain the observed yellow and orange phenotypes...
May 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28524767/immune-biomarkers-in-older-adults-role-of-physical-activity
#8
Vanessa Valdiglesias, María Sánchez-Flores, Ana Maseda, Laura Lorenzo-López, Diego Marcos-Pérez, Ana López-Cortón, Barbara Strasser, Dietmar Fuchs, Blanca Laffon, José C Millán-Calenti, Eduardo Pásaro
Aging is associated with a decline in the normal functioning of the immune system. Several studies described the relationship between immunological alterations, including immunosenescence and inflammation, and aging or age-related outcomes, such as sarcopenia, depression, and neurodegenerative disorders. Physical activity is known to improve muscle function and to exert a number of benefits on older adult health, including reduced risk for heart and metabolic system chronic diseases. However, the positive influence of physical activity on the immune system has not been elucidated...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28523591/assessment-of-the-neuroprotective-effects-of-arginine-rich-protamine-peptides-poly-arginine-peptides-r12-cyclic-r22-and-arginine-tryptophan-containing-peptides-following-in-vitro-excitotoxicity-and-or-permanent-middle-cerebral-artery-occlusion-in-rats
#9
Bruno P Meloni, Diego Milani, Jane L Cross, Vince W Clark, Adam B Edwards, Ryan S Anderton, David J Blacker, Neville W Knuckey
We have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine peptides containing tryptophan or other amino acids (phenylalanine, tyrosine, glycine or leucine) in in vitro glutamic acid excitotoxicity and in vivo rat permanent middle cerebral artery occlusion models of stroke...
May 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28520912/lower-levels-of-cervicovaginal-tryptophan-are-associated-with-natural-clearance-of-chlamydia-in-women
#10
Stephen J Jordan, Kristin M Olson, Stephen Barnes, Landon S Wilson, Taylor F Berryhill, Rakesh Bakshi, LaDraka' T Brown, Christen G Press, William M Geisler
Chlamydia trachomatis (Ct) infection causes significant morbidity. In vitro studies demonstrate Ct growth inhibition occurs by interferon-gamma (IFN-γ)-mediated depletion of intracellular tryptophan, and some Ct strains utilize extracellular indole to restore tryptophan levels. Whether tryptophan levels are associated with Ct infection in clearance humans remains unknown. We evaluated tryptophan, indole, and IFN-γ levels in cervicovaginal lavages from women with either naturally cleared Ct infection or persisting Ct infection...
May 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28518204/integrated-metabolomics-and-metallomics-analyses-in-acute-coronary-syndrome-patients
#11
Xuejiao Yin, Leonardo Pinto de Carvalho, Mark Y Chan, Sam Fong Yau Li
Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality. Accurate risk prediction in ACS patients is critically important for helping clinicians make therapeutic decisions, such as recommending a more aggressive intervention and intensive follow-up. However, risk stratification in ACS patients remains challenging, and the identification of novel predictors is necessary for improving the prognostic prediction in ACS patients. We employed metallomics and untargeted metabolomics approaches to discover new biomarkers from the plasma samples of 20 ACS patients and 20 non-ACS patients...
May 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28516405/characterization-of-dissolved-organic-matter-in-an-urbanized-estuary-located-in-northeastern-brazil
#12
Maria de Lara Palmeira de Macedo Arguelho, José do Patrocínio Hora Alves, Adnívia Santos Costa Monteiro, Carlos Alexandre Borges Garcia
The Sal River estuary, which is located in the state of Sergipe, Northeastern Brazil, stands out as an urban estuary, anthropogenically impacted by untreated and treated wastewater discharge. Synchronous fluorescence spectroscopy and measurement of dissolved organic carbon (DOC) were used for characterization of dissolved organic matter (DOM) in the estuarine water. Dissolved organic carbon concentrations ranged from 7.5 to 19.0 mg L(-1) and, in general, the highest values were recorded during dry season...
June 2017: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/28516297/subcritical-water-hydrolysis-of-peptides-amino-acid-side-chain-modifications
#13
Thomas Powell, Steve Bowra, Helen J Cooper
Previously we have shown that subcritical water may be used as an alternative to enzymatic digestion in the proteolysis of proteins for bottom-up proteomics. Subcritical water hydrolysis of proteins was shown to result in protein sequence coverages greater than or equal to that obtained following digestion with trypsin; however, the percentage of peptide spectral matches for the samples treated with trypsin were consistently greater than for those treated with subcritical water. This observation suggests that in addition to cleavage of the peptide bond, subcritical water treatment results in other hydrolysis products, possibly due to modifications of amino acid side chains...
May 17, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28515297/attenuation-of-foot-and-mouth-disease-virus-by-engineering-viral-polymerase-fidelity
#14
Devendra K Rai, Fayna Diaz-San Segundo, Grace Campagnola, Anna Keith, Elizabeth A Schafer, Anna Kloc, Teresa de Los Santos, Olve Peersen, Elizabeth Rieder
Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp or 3D(pol)) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allows FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D(pol) in combination with prior results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514856/cell-adhesion-on-rgd-displaying-knottins-with-varying-number-of-tryptophan-amino-acids-to-tune-the-affinity-for-assembly-on-cucurbit-8-uril-surfaces
#15
Shrikrishnan Sankaran, Emanuela Cavatorta, Jurriaan Huskens, Pascal Jonkheijm
Cell adhesion is studied on multivalent knottins, displaying RGD ligands with high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV2+). The binding affinity of the knottins with CB[8] and MV2+ surfaces was evaluated using surface plasmon resonance spectroscopy...
May 18, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28512916/regulation-of-bone-mass-through-pineal-derived-melatonin-mt2-pathway
#16
Kunal Sharan, Kirsty Lewis, Takahisa Furukawa, Vijay K Yadav
Tryptophan, an essential amino acid through a series of enzymatic reactions gives rise to various metabolites viz., serotonin and melatonin that regulate distinct biological functions. We show here that tryptophan metabolism in the pineal gland favors bone mass accrual through production of melatonin, a pineal-derived neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes the first step in the melatonin biosynthesis lead to a decrease in melatonin levels and a low bone mass due to an isolated decrease in bone formation while bone resorption parameters remained unaffected...
May 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28512464/insights-into-the-mechanism-of-proliferation-on-the-special-microbes-mediated-by-phenolic-acids-in-the-radix-pseudostellariae-rhizosphere-under-continuous-monoculture-regimes
#17
Hongmiao Wu, Junjian Xu, Juanying Wang, Xianjin Qin, Linkun Wu, Zhicheng Li, Sheng Lin, Weiwei Lin, Quan Zhu, Muhammad U Khan, Wenxiong Lin
As potent allelochemicals, phenolic acids are believed to be associated with replanting disease and cause microflora shift and structural disorder in the rhizosphere soil of continuously monocultured Radix pseudostellariae. The transcriptome sequencing was used to reveal the mechanisms underlying the differential response of pathogenic bacterium Kosakonia sacchari and beneficial bacterium Bacillus pumilus on their interactions with phenolic acids, the main allelochemicals in root exudates of R. pseudostellariae in the monoculture system...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28511977/role-of-acetylcholine-and-serotonin-in-novelty-processing-using-an-oddball-paradigm
#18
S Caldenhove, L G J M Borghans, A Blokland, A Sambeth
The processing of novel stimuli is known to take place in the hippocampus and frontal cortex, and is influenced by the cholinergic system. This ability is crucial to help detect changes in the environment and adapt behavior accordingly. Previous research has shown that acetylcholine (ACh) can interact with serotonin (5-HT) at the hippocampal level, which may have consequences for cognitive functioning. However, little is known about the exact nature of this ACh and 5-HT interaction as well their possible interactive effects on novelty processing...
May 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28511809/characterisation-of-the-selective-binding-of-antibiotics-vancomycin-and-teicoplanin-by-the-vans-receptor-regulating-type-a-vancomycin-resistance-in-the-enterococci
#19
C S Hughes, E Longo, M K Phillips-Jones, R Hussain
A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanRASA two-component system, comprising the histidine sensor kinase VanSA and the partner response regulator VanRA. The nature of the activating ligand for VanSA has not been identified, therefore this work sought to identify and characterise ligand(s) for VanSA. In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanSA protein...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28511640/tryptophan-catabolism-and-immune-activation-in-primary-and-chronic-hiv-infection
#20
Marco Gelpi, Hans J Hartling, Per M Ueland, Henrik Ullum, Marius Trøseid, Susanne D Nielsen
BACKGROUND: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation. METHODS: Prospective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (<200 CD4+ T cells/μL, N = 19))...
May 16, 2017: BMC Infectious Diseases
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