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https://www.readbyqxmd.com/read/28106753/naphthalimides-selectively-inhibit-the-activity-of-bacterial-replicative-dna-ligases-and-display-bactericidal-effects-against-tubercle-bacilli
#1
Malgorzata Korycka-Machala, Marcin Nowosielski, Aneta Kuron, Sebastian Rykowski, Agnieszka Olejniczak, Marcin Hoffmann, Jaroslaw Dziadek
The DNA ligases, enzymes that seal breaks in the backbones of DNA, are essential for all organisms, however bacterial ligases essential for DNA replication use β-nicotinamide adenine dinucleotide as their co-factor, whereas those that are essential in eukaryotes and viruses use adenosine-5'-triphosphate. This fact leads to the conclusion that NAD⁺-dependent DNA ligases in bacteria could be targeted by their co-factor specific inhibitors. The development of novel alternative medical strategies, including new drugs, are a top priority focus areas for tuberculosis research due to an increase in the number of multi-drug resistant as well as totally drug resistant tubercle bacilli strains...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28104455/a-novel-role-for-endothelial-tetrahydrobiopterin-in-mitochondrial-redox-balance
#2
Jade Bailey, Andrew Shaw, Roman Fischer, Brent J Ryan, Benedikt M Kessler, James McCullagh, Richard Wade-Martins, Keith M Channon, Mark J Crabtree
The redox co-factor tetrahydrobiopterin (BH4) regulates nitric oxide (NO) and reactive oxygen species (ROS) production by endothelial NOS (eNOS) and is an important redox-dependent signalling molecule in the endothelium. Loss of endothelial BH4 is observed in cardiovascular disease (CVD) states and results in decreased NO and increased superoxide (O2(-)) generation via eNOS uncoupling. Genetic mouse models of augmented endothelial BH4 synthesis have shown proof of concept that endothelial BH4 can alter CVD pathogenesis...
January 16, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28103242/genome-wide-binding-of-posterior-hoxa-d-transcription-factors-reveals-subgrouping-and-association-with-ctcf
#3
Ivana Jerković, Daniel M Ibrahim, Guillaume Andrey, Stefan Haas, Peter Hansen, Catrin Janetzki, Irene González Navarrete, Peter N Robinson, Jochen Hecht, Stefan Mundlos
Homeotic genes code for key transcription factors (HOX-TFs) that pattern the animal body plan. During embryonic development, Hox genes are expressed in overlapping patterns and function in a partially redundant manner. In vitro biochemical screens probing the HOX-TF sequence specificity revealed largely overlapping sequence preferences, indicating that co-factors might modulate the biological function of HOX-TFs. However, due to their overlapping expression pattern, high protein homology, and insufficiently specific antibodies, little is known about their genome-wide binding preferences...
January 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28096217/high-throughput-analysis-reveals-novel-maternal-germline-rnas-crucial-for-primordial-germ-cell-preservation-and-proper-migration
#4
Dawn A Owens, Amanda M Butler, Tristan H Aguero, Karen M Newman, Derek Van Booven, Mary Lou King
During oogenesis, hundreds of maternal RNAs are selectively localized to the animal or vegetal pole, including determinants of somatic and germline fates. Although microarray analysis has identified localized determinants, it is not comprehensive and is limited to known transcripts. Here, we utilized high-throughput RNA-sequencing analysis to comprehensively interrogate animal and vegetal pole RNAs in the fully grown Xenopus laevis oocyte. We identified 411 (198 annotated) and 27 (15 annotated) enriched mRNAs at the vegetal and animal pole, respectively...
January 15, 2017: Development
https://www.readbyqxmd.com/read/28094105/sonographic-alteration-of-substantia-nigra-is-related-to-parkinsonism-predominant-course-of-x-linked-dystonia-parkinsonism
#5
Uwe Walter, Raymond Rosales, Alessandro Rocco, Ana Westenberger, Aloysius Domingo, Criscely L Go, Norbert Brüggemann, Christine Klein, Lillian V Lee, Dirk Dressler
INTRODUCTION: X-linked recessive dystonia-parkinsonism (XDP, DYT3) is highly prevalent in the Philippines and manifests with varying phenotype. We sought to evaluate the significance of transcranial brain sonography as a biomarker for parkinsonism-predominant phenotype. METHODS: 90 Filipino participants were enrolled into a cross-sectional study: 39 patients with XDP, 21 asymptomatic first-degree relatives of XDP patients, and 30 healthy control subjects. Echogenicity of the substantia nigra and the lenticular nuclei was digitally quantified...
January 10, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28093457/functional-analysis-of-the-mammalian-rna-ligase-for-ire1-in-the-unfolded-protein-response
#6
Juthakorn Poothong, Witoon Tirasophon, Randal J Kaufman
The unfolded protein response (UPR) is a conserved signaling pathway activated upon the accumulation of unfolded proteins within the endoplasmic reticulum (ER), termed ER stress. Upon ER stress, HAC1 / XBP1 undergoes exon/intron specific excision by IRE1 to remove an intron and liberate the 5' and 3' exons. In yeast, the 5' and 3' HAC1 exons are subsequently ligated by tRNA ligase (Rlg1p) whereas XBP1 ligation in mammalian cells is catalyzed by a recently identified ligase, RtcB. In this study, the RNA ligase activity of the human RtcB involved in the unconventional splicing of XBP1 / HAC1 mRNA was explored in an rlg1-100 mutant yeast strain...
January 16, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28090671/lgp2-plays-an-essential-role-in-hcv-infection-induced-interferon-responses
#7
Lei Hei, Jin Zhong
: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are cytosolic pattern recognition receptors (PRR) that detect non-self RNA and activate downstream interferon (IFN) signaling. One of the RLRs, Laboratory of genetics and physiology 2 (LGP2) was originally thought to be a negative feedback regulator in RIG-I signaling pathway, but growing evidence indicates LGP2 is one co-factor of Melanoma Differentiation-Associated protein 5 (MDA5) in MDA5-mediated IFN signaling activation...
January 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28089968/prevalence-of-anti-infliximab-antibodies-and-their-associated-co-factors-in-children-with-refractory-arthritis-and-or-uveitis-a-retrospective-longitudinal-cohort-study
#8
Florence A Aeschlimann, Felix Angst, Kevin D Hofer, Elvira Cannizzaro Schneider, Silke Schroeder-Kohler, Roger Lauener, Desirée van der Kleij, Theo Rispens, Rotraud K Saurenmann
OBJECTIVE: Infliximab (IFX) is a monoclonal tumor necrosis factor-α-inhibiting antibody used in children with refractory arthritis and uveitis. Immunogenicity is associated with a lack of clinical response and infusion reactions in adults; data on immunogenicity in children treated with IFX for rheumatic diseases are scarce. We aimed to describe the prevalence of anti-IFX antibodies and determine co-factors associated with anti-IFX antibodies in children with inflammatory rheumatic and ocular diseases...
January 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28077791/carcinoma-risk-variant-of-ebna1-deregulates-epstein-barr-virus-episomal-latency
#9
Jayaraju Dheekollu, Kimberly Malecka, Andreas Wiedmer, Henri-Jacques Delecluse, Alan Ks Chiang, Dario C Altieri, Troy E Messick, Paul M Lieberman
Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28072826/rna-dependent-rna-polymerases-of-both-virulent-and-benign-rabbit-caliciviruses-induce-striking-rearrangement-of-golgi-membranes
#10
Nadya Urakova, Tanja Strive, Michael Frese
The extremely pathogenic Rabbit haemorrhagic disease virus (RHDV) and the completely benign Rabbit calicivirus (RCV) are closely related members of the genus Lagovirus (family Caliciviridae). The molecular mechanisms that determine the dramatic difference in virulence are unknown, but indirect evidence suggests that different properties of their RNA-dependent RNA polymerases (RdRps) may at least partially be responsible for the contrasting phenotypes. Here we report that the unusual ability of the RHDV RdRp to induce a striking rearrangement of the Golgi network is not specific to RHDV, but a common feature of virulent and benign rabbit caliciviruses alike...
2017: PloS One
https://www.readbyqxmd.com/read/28065867/cloning-expression-purification-and-biophysical-analysis-of-two-putative-halogenases-from-the-glycopeptide-a47-934-gene-cluster-of-streptomyces-toyocaensis
#11
Tabata P Cardoso, Larissa A de Sá, Priscila Dos S Bury, Sair M Chavez-Pacheco, Marcio V B Dias
Glycopeptides are an important class of antibiotics used in the treatment of several infections, including those caused by methicillin resistant Staphylococcus aureus. Glycopeptides are biosynthesized by a Non Ribosomal Peptide Synthase (NRPS) and the resulting peptide precursors are decorated by several tailoring enzymes, such as halogenases and glycosyltransferases. These enzymes are important targets of protein engineering to produce new derivatives of known antibiotics. Herein we show the production of two putative halogenases, denominated StaI and StaK, involved in the biosynthesis of the glycopeptide A47,934 in Streptomyces toyocaensis NRRL 15,009...
January 5, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28065841/the-neurotoxic-mechanisms-of-amphetamine-step-by-step-for-striatal-dopamine-depletion
#12
Che-Se Tung, Shang-Tang Chang, Chuen-Lin Huang, Nai-Kuei Huang
Amphetamine (AMPH) is a commonly abused psychostimulant that induces neuronal cell death/degeneration in humans and experimental animals. Although multiple neurotoxic mechanisms of AMPH have been intensively investigated, the interplay between these mechanisms has remained elusive. In this study, we used a rat model of AMPH-induced long-lasting striatal dopamine (DA) depletion and identified mechanisms of neurotoxicity, energy failure, excitotoxicity, and oxidative stress. Pretreatment with nicotinamide (NAM, a co-factor for the electron transport chain) blocked AMPH-induced free radical formation, energy failure, and striatal DA decrease...
January 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28063999/relationship-between-intracellular-ph-metabolic-co-factors-and-caspase-3-activation-in-cancer-cells-during-apoptosis
#13
Tatiana F Sergeeva, Marina V Shirmanova, Olga A Zlobovskaya, Alena I Gavrina, Varvara V Dudenkova, Maria M Lukina, Konstantin A Lukyanov, Elena V Zagaynova
A complex cascade of molecular events occurs in apoptotic cells but cell-to-cell variability significantly complicates determination of the order and interconnections between different processes. For better understanding of the mechanisms of programmed cell death, dynamic simultaneous registration of several parameters is required. In this paper we used multiparameter fluorescence microscopy to analyze energy metabolism, intracellular pH and caspase-3 activation in living cancer cells in vitro during staurosporine-induced apoptosis...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28057741/factor-viii-v-c-domain-swaps-reveal-discrete-c-domain-roles-in-factor-viii-function-and-intracellular-trafficking
#14
Eduard H T M Ebberink, Eveline A M Bouwens, Esther Bloem, Mariëtte Boon-Spijker, Maartje Van den Biggelaar, Jan Voorberg, Alexander B Meijer, Koen Mertens
Factor VIII C-domains are believed to contain specific function in co-factor activity and in interaction with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study we furthermore addressed the contribution of individual factor VIII C-domains in intracellular targeting, von Willebrand factor binding and co-factor activity by factor VIII/V C-domain swapping...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28050066/antiphospholipid-syndrome-a-diagnostic-challenge
#15
REVIEW
R S Mallhi, Neerja Kushwaha, T Chatterjee, J Philip
The antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilic disorder that is characterized by thrombosis (venous, arterial and microvascular) and obstetric morbidity due to a diverse family of antibodies against phospholipid-binding proteins present in plasma. The term antiphospholipid antibody is actually a misnomer as the antibodies are not against the phospholipid per se, but target the plasma protein co-factors, which bind to anionic PLs. The exact etiology has not been elucidated and is multifactorial...
December 2016: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#16
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28042827/bag2-interferes-with-chip-mediated-ubiquitination-of-hsp72
#17
Bianca Schönbühler, Verena Schmitt, Heike Huesmann, Andreas Kern, Martin Gamerdinger, Christian Behl
The maintenance of cellular proteostasis is dependent on molecular chaperones and protein degradation pathways. Chaperones facilitate protein folding, maturation, and degradation, and the particular fate of a misfolded protein is determined by the interaction of chaperones with co-chaperones. The co-factor CHIP (C-terminus of HSP70-inteacting protein, STUB1) ubiquitinates chaperone substrates and directs proteins to the cellular degradation systems. The activity of CHIP is regulated by two co-chaperones, BAG2 and HSPBP1, which are potent inhibitors of the E3 ubiquitin ligase activity...
December 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28031463/new-insights-into-structural-disorder-in-human-respiratory-syncytial-virus-phosphoprotein-and-implications-for-binding-of-protein-partners
#18
Nelson Pereira, Christophe Cardone, Safa Lassoued, Marie Galloux, Jenna Fix, Nadine Assrir, Ewen Lescop, François Bontems, Jean-François Eléouët, Christina Sizun
Phosphoprotein is the main co-factor of the viral RNA polymerase of Mononegavirales. It is involved in multiple interactions that are essential for the polymerase function. Most prominently it positions the polymerase complex onto the nucleocapsid, but also acts as a chaperone for the nucleoprotein. Mononegavirales phosphoproteins lack sequence conservation, but contain all large disordered regions. We show here that N-and C-terminal intrinsically disordered regions account for 80% of the phosphoprotein of the Respiratory Syncytial Virus...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28009091/in-vitro-spontaneous-contractile-activity-of-colonic-smooth-muscle-in-naive-lewis-rats-acute-effect-of-gonadal-hormones
#19
Christine Baumgartner, Thomas Hubacher, Magali Krayer, Juergen Gschossmann
AIM: Functional gastrointestinal disorders affect females more often. Changes in colonic motility may be etiological co-factors for the clinical symptoms. The aim of the present study was to analyze the influence of gonadal hormones on colonic contractile activity. METHODS: In vitro measurements of colonic contractile activity in longitudinal smooth muscle strips of female and male Lewis rats were performed in an organ chamber experiment set-up. After administration of a gonadal hormone (estrogen (EST), progesterone (PROG) and testosterone (TEST)) or ethanol (ETH) solution as control, stimulation with acetylcholine (ACh) or inhibition with norepinephrine (NE) was performed...
December 23, 2016: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28007937/directed-evolution-of-p450cin-for-mediated-electron-transfer
#20
Ketaki D Belsare, Thomas Horn, Anna Joëlle Ruff, Ronny Martinez, Anders Magnusson, Dirk Holtmann, Jens Schrader, Ulrich Schwaneberg
Directed evolution is a powerful method to optimize enzyme properties for application demands. Interesting targets are P450 monooxygenases which catalyze the stereo- and regiospecific hydroxylation of chemically inert C-H bonds. Synthesis employing P450s under cell-free reaction conditions is limited by low total turnover numbers, enzyme instability, low product yields and the requirement of the expensive co-factor NADPH. Bioelectrocatalysis is an alternative to replace NADPH in cell-free P450-catalyzed reactions...
December 22, 2016: Protein Engineering, Design & Selection: PEDS
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