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https://www.readbyqxmd.com/read/28727234/kynurenine-a-tryptophan-metabolite-that-accumulates-with-age-induces-bone-loss
#1
Mona El Refaey, Meghan E McGee-Lawrence, Sadanand Fulzele, Eileen J Kennedy, Wendy B Bollag, Mohammed Elsalanty, Qing Zhong, Ke-Hong Ding, Nathaniel G Bendzunas, Xing-Ming Shi, Jianrui Xu, William D Hill, Maribeth H Johnson, Monte Hunter, Jessica L Pierce, Kanglun Yu, Mark W Hamrick, Carlos M Isales
Age-dependent bone loss occurs in humans and in several animal species, including rodents. The underlying causal mechanisms are probably multifactorial, although an age-associated increase in the generation of reactive oxygen species has been frequently implicated. We previously reported that aromatic amino acids function as antioxidants and are anabolic for bone and that they may potentially play a protective role in an aging environment. We hypothesized that upon oxidation the aromatic amino acids would not only lose their anabolic effects but also potentially become a catabolic byproduct...
July 20, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#2
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28724760/uv-radiation-activates-toll-like-receptor-9-expression-in-primary-human-keratinocytes-an-event-inhibited-by-human-papillomavirus-type-38-e6-and-e7-oncoproteins
#3
Laura Pacini, Maria Grazia Ceraolo, Assunta Venuti, Giusi Melita, Uzma A Hasan, Rosita Accardi, Massimo Tommasino
Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergise with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes (PHKs) as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720200/influence-of-erythrocyte-aggregation-on-radial-migration-of-platelet-sized-spherical-particles-in-shear-flow
#4
Cyrille Guilbert, Boris Chayer, Louise Allard, François T H Yu, Guy Cloutier
Blood platelets when activated are involved in the mechanisms of hemostasis and thrombosis, and their migration toward injured vascular endothelium necessitates interaction with red blood cells (RBCs). Rheology co-factors such as a high hematocrit and a high shear rate are known to promote platelet mass transport toward the vessel wall. Hemodynamic conditions promoting RBC aggregation may also favor platelet migration, particularly in the venous system at low shear rates. The aim of this study was to confirm experimentally the impact of RBC aggregation on platelet-sized micro particle migration in a Couette flow apparatus...
July 5, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28712805/direct-spectroscopic-detection-of-atp-turnover-reveals-mechanistic-divergence-of-abc-exporters
#5
Alberto Collauto, Smriti Mishra, Aleksei Litvinov, Hassane S Mchaourab, Daniella Goldfarb
We have applied high-field (W-band) pulse electron-nuclear double resonance (ENDOR) and electron-electron double resonance (ELDOR)-detected nuclear magnetic resonance (EDNMR) to characterize the coordination sphere of the Mn(2+) co-factor in the nucleotide binding sites (NBSs) of ABC transporters. MsbA and BmrCD are two efflux transporters hypothesized to represent divergent catalytic mechanisms. Our results reveal distinct coordination of Mn(2+) to ATP and transporter residues in the consensus and degenerate NBSs of BmrCD...
July 13, 2017: Structure
https://www.readbyqxmd.com/read/28710890/food-allergy-phenotypes-the-key-to-personalized-therapy
#6
Antoine Deschildre, Stéphanie Lejeune, Mélanie Cap, Sophie Flammarion, Line Jouannic, Flore Amat, Jocelyne Just
Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE mediated FAs), and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, co-factors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management...
July 15, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28710857/ros-mediated-selection-for-increased-nadph-availability-in-escherichia-coli
#7
REVIEW
T Steele Reynolds, Colleen M Courtney, Keesha E Erickson, Lisa M Wolfe, Anushree Chatterjee, Prashant Nagpal, Ryan T Gill
The economical production of chemicals and fuels by microbial processes remains an intense area of interest in biotechnology. A key limitation in such efforts concerns the availability of key co-factors, in this case NADPH, required for target pathways. Many of the strategies pursued for increasing NADPH availability in Escherichia coli involve manipulations to the central metabolism, which can create redox imbalances and overall growth defects. In this study we used a reactive oxygen species based selection to search for novel methods of increasing NADPH availability...
July 15, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28705199/the-m-phase-specific-hyperphosphorylation-of-staufen2-involved-the-cyclin-dependent-kinase-cdk1
#8
Rémy Beaujois, Elizabeth Ottoni, Xin Zhang, Christina Gagnon, Sami HSine, Stéphanie Mollet, Wildriss Viranaicken, Luc DesGroseillers
BACKGROUND: Staufen2 (STAU2) is an RNA-binding protein involved in the post-transcriptional regulation of gene expression. This protein was shown to be required for organ formation and cell differentiation. Although STAU2 functions have been reported in neuronal cells, its role in dividing cells remains deeply uncharacterized. Especially, its regulation during the cell cycle is completely unknown. RESULTS: In this study, we showed that STAU2 isoforms display a mitosis-specific slow migration pattern on SDS-gels in all tested transformed and untransformed cell lines...
July 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28688209/quantifying-the-efficiency-of-saccharomyces-cerevisiae-translocation-tags
#9
Amy M Ehrenworth, Mitchell A Haines, Amy Wong, Pamela Peralta-Yahya
Compartmentalization of metabolic pathways into organelles of the yeast Saccharomyces cerevisiae has been used to improve chemical production. Pathway compartmentalization aids chemical production by bringing enzymes into close proximity to one another, placing enzymes near key starting metabolites or essential co-factors, increasing the effective concentration of metabolic intermediates, and providing a more suitable chemical environment for enzymatic activity. Although several translocation tags have been used to localize enzymes to different yeast organelles, their translocation efficiencies have not been quantified...
July 8, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28686580/upregulation-of-lyar-induces-neuroblastoma-cell-proliferation-and-survival
#10
Yuting Sun, Bernard Atmadibrata, Denise Yu, Matthew Wong, Bing Liu, Nicholas Ho, Dora Ling, Andrew E Tee, Jenny Wang, Imran N Mungrue, Pei Y Liu, Tao Liu
The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and consequently causing cell proliferation. Paradoxically, N-Myc is well known to induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N-Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The nuclear zinc finger protein LYAR has recently been shown to modulate gene expression by forming a protein complex with the protein arginine methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene expression by binding to its gene promoter...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28684647/hypersensitivity-to-antipyretics-pathogenesis-diagnosis-and-management
#11
REVIEW
Q U Lee
Antipyretics are commonly prescribed drugs and hypersensitivity occurs at rates of 0.01% to 0.3%. Hypersensitivity can be due to immune mechanisms that include type I to IV hypersensitivity. Type I hypersensitivity results from specific immunoglobulin E production following sensitisation on first exposure. Subsequent exposures elicit degranulation of mast cells, culminating an immediate reaction. Non-type I hypersensitivity is a delayed reaction that involves various effector cells, resulting in maculopapular rash, fixed drug eruptions, drug reaction with eosinophilia and systemic symptoms, and Stevens-Johnson syndrome/toxic epidermal necrolysis...
July 7, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28680153/disruption-of-key-nadh-binding-pocket-residues-of-the-mycobacterium-tuberculosis-inha-affects-dd-coa-binding-ability
#12
Daniel J Shaw, Kirsty Robb, Beatrice V Vetter, Madeline Tong, Virginie Molle, Neil T Hunt, Paul A Hoskisson
Tuberculosis (TB) is a global health problem that affects over 10 million people. There is an urgent need to develop novel antimicrobial therapies to combat TB. To achieve this, a thorough understanding of key validated drug targets is required. The enoyl reductase InhA, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-TB drug isoniazid. To better understand the activity of this protein a series of mutants, targeted to the NADH co-factor binding pocket were created...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680107/a-novel-synthetic-approach-of-cerium-oxide-nanoparticles-with-improved-biomedical-activity
#13
Fanny Caputo, Marta Mameli, Andrzej Sienkiewicz, Silvia Licoccia, Francesco Stellacci, Lina Ghibelli, Enrico Traversa
Cerium oxide nanoparticles (CNPs) are novel synthetic antioxidant agents proposed for treating oxidative stress-related diseases. The synthesis of high-quality CNPs for biomedical applications remains a challenging task. A major concern for a safe use of CNPs as pharmacological agents is their tendency to agglomerate. Herein we present a simple direct precipitation approach, exploiting ethylene glycol as synthesis co-factor, to synthesize at room temperature nanocrystalline sub-10 nm CNPs, followed by a surface silanization approach to improve nanoparticle dispersibility in biological fluids...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676501/lifespan-extension-by-peroxidase-dual-oxidase-mediated-ros-signaling-through-pyrroloquinoline-quinone-in-c-elegans
#14
Hiroyuki Sasakura, Hiroki Moribe, Masahiko Nakano, Kazuto Ikemoto, Kosei Takeuchi, Ikue Mori
Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase/dual oxidase system, which could extend lifespan in Caenorhabditis elegans (C. elegans). A redox co-factor, pyrroloquinoline quinone (PQQ), activates dual oxidase (DUOX)/BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase/MLT-7, eventually ensuring the adequate levels of ROS...
July 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28675645/adult-onset-nocturnal-enuresis-identifying-causes-cofactors-and-impact-on-quality-of-life
#15
Dominic Lee, Benjamin E Dillon, Gary E Lemack
OBJECTIVES: The objectives of the present study were: (i) Evaluate common co-pathologies associated with, and potentially contributing to adult onset Nocturnal enuresis (NE) in a tertiary referral population; and (ii) quantify its impact on QoL with validated questionnaires. METHODS: Following Institutional Review Board approval, patients with adult onset NE were reviewed with history, physical examination, urodynamic studies, questionnaires: Overactive bladder questionnaire short-form (OAB-qSF), Urogenital Distress Inventory (UDI-6), AUA symptom score (AUA-SS) and Patient Global Impression scale (PGIS)...
July 3, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/28665962/biochemical-characterization-of-functional-domains-of-the-chaperone-cosmc
#16
Melinda S Hanes, Kelley W Moremen, Richard D Cummings
Cosmc is an endoplasmic reticulum chaperone necessary for normal protein O-GalNAc glycosylation through regulation of T-synthase, its single client. Loss-of-function of Cosmc results in expression of the Tn antigen, which is associated with multiple human diseases including cancer. Despite intense interest in dysregulated expression of the Tn antigen, little is known about the structure and function of Cosmc, including domain organization, secondary structure, oligomerization, and co-factors. Limited proteolysis experiments show that Cosmc contains a structured N-terminal domain (CosmcΔ256), and biochemical characterization of CosmcΔ256 reveals wild type chaperone activity...
2017: PloS One
https://www.readbyqxmd.com/read/28656748/amp-binding-stabilizes-the-ktn-domain-of-the-shewanella-denitrificans-kef-potassium-efflux-system
#17
Christos Pliotas, Samuel C Grayer, Silvia Ekkerman, Anthony Kn Chan, Jess Healy, Phedra Marius, Wendy Bartlett, Amjad Khan, Wilian Augusto Cortopassi, Shane A Chandler, Tim Rasmussen, Justin Lp Benesch, Robert S Paton, Timothy D W Claridge, Samantha Miller, Ian Rylance Booth, James H Naismith, Stuart J Conway
Ligand binding is one of the most fundamental properties of proteins. Ligand functions fall into three basic types: substrates, regulatory molecules, and co-factors essential to protein stability, reactivity, or enzyme-substrate complex formation. The regulation of potassium ion movement in bacteria is predominantly under the control of regulatory ligands that gate the relevant channels and transporters, which possess subunits or domains that contain Rossmann folds (RFs). Here we demonstrate that AMP is bound to both RFs of the dimeric bacterial Kef potassium efflux system (Kef), where it plays a structural role...
June 28, 2017: Biochemistry
https://www.readbyqxmd.com/read/28651373/sex-dependent-differences-in-liver-and-gut-metabolomic-profiles-with-acarbose-and-calorie-restriction-in-c57bl-6-mice
#18
Victoria K Gibbs, Rachel A Brewer, Nathan D Miyasaki, Amit Patki, Daniel L Smith
Acarbose, an alpha-glucosidase inhibitor used in treating type 2 diabetes, impairs complex carbohydrate digestion and absorption and extends lifespan in mice (without a requisite reduction in food intake). To assess sex-differential effects coincident with calorie restriction versus a non-restricted longevity enhancing intervention, we evaluated the metabolite profiles (by LC/MS) from livers and cecal contents of C57BL/6J mice (n=4/sex/group,) which were maintained for 10 months under one of three diet treatments: ad libitum control diet (CON), ad libitum control diet containing 0...
June 23, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28649368/wnt-target-genes-and-where-to-find-them
#19
REVIEW
Aravinda-Bharathi Ramakrishnan, Ken M Cadigan
Wnt/β-catenin signaling is highly conserved throughout metazoans, is required for numerous essential events in development, and serves as a stem cell niche signal in many contexts. Misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt stimulation results in stabilization and nuclear import of β-catenin, which then acts as a transcriptional co-activator. Transcription factors of the T-cell family (TCF) are the best-characterized nuclear binding partners of β-catenin and mediators of Wnt gene regulation...
2017: F1000Research
https://www.readbyqxmd.com/read/28647601/benzaldehyde-dehydrogenase-driven-phytoalexin-biosynthesis-in-elicitor-treated-pyrus-pyrifolia-cell-cultures
#20
Shashank Sagar Saini, Deepa Teotia, Mariam Gaid, Anirudh Thakur, Ludger Beerhues, Debabrata Sircar
Pyrus pyrifolia (Asian pear) cell cultures respond to yeast extract (YE) treatment by accumulating benzoate-derived biphenyl phytoalexins, namely, noraucuparin and aucuparin. Biphenyl phytoalexins are defense-marker metabolites of the sub-tribe Malinae of the family Rosaceae. The substrates for biphenyl biosynthesis are benzoyl-CoA and malonyl-CoA, which combine in the presence of biphenyl synthase (BIS) to produce 3,5-dihydroxybiphneyl. In the non-β-oxidative pathway, benzoyl-CoA is directly derived from benzoic acid in a reaction catalyzed by benzoate-CoA ligase (BZL)...
June 13, 2017: Journal of Plant Physiology
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