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https://www.readbyqxmd.com/read/28802127/investigations-on-the-molecular-mode-of-action-of-the-novel-immunostimulator-zelnate-activation-of-the-cgas-sting-pathway-in-mammalian-cells
#1
Thomas Ilg
Bovine respiratory disease (BRD) is usually prevented or treated with vaccines and/or antibiotics. The use of antibiotics is, however, of concern due to the potential promotion of microbial resistance and the occurrence of residues. Recently an alternative aid in the treatment of BRD, the cationic lipid/bacterial plasmid DNA liposome-based immunomodulator ZelNate, has entered the veterinary market. In the present study, we provide data on the molecular mode of action of ZelNate. Despite the presence of numerous non-methylated CpG motifs in its plasmid DNA, ZelNate proved to be inactive on human and mouse toll-like receptor 9 (TLR9) in cell culture, in both recombinant and natural cellular receptor settings...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28781907/development-and-validation-of-a-stability-indicating-hplc-method-for-the-simultaneous-determination-of-florfenicol-and-flunixin-meglumine-combination-in-an-injectable-solution
#2
Nidal Batrawi, Hani Naseef, Fuad Al-Rimawi
The combination of the powerful antimicrobial agent florfenicol and the nonsteroidal anti-inflammatory flunixin meglumine is used for the treatment of bovine respiratory disease (BRD) and control of BRD-associated pyrexia, in beef and nonlactating dairy cattle. This study describes the development and validation of an HPLC-UV method for the simultaneous determination of florfenicol and flunixin, in an injectable preparation with a mixture of excipients. The proposed RP-HPLC method was developed by a reversed phase- (RP-) C18e (250 mm × 4...
2017: Journal of Analytical Methods in Chemistry
https://www.readbyqxmd.com/read/28768141/a-randomized-trial-to-assess-the-effect-of-fluoroquinolone-metaphylaxis-on-the-fecal-prevalence-and-quinolone-susceptibilities-of-salmonella-and-campylobacter-in-feedlot-cattle
#3
Ashley B Smith, David G Renter, Natalia Cernicchiaro, Xiaorong Shi, Jason S Nickell, Daniel J Keil, T G Nagaraja
The study objective was to determine effects of fluoroquinolone metaphylaxis on fecal prevalence of Salmonella and Campylobacter and fecal prevalence of quinolone-resistant Salmonella and Campylobacter in feedlot cattle. On Day 0, cattle (n = 288) at risk for bovine respiratory disease (BRD) were randomly assigned to either a nontreated control pen (12 pens) or a fluoroquinolone-treated (enrofloxacin; Baytril(®) 100) pen (12 pens). Rectal fecal samples were collected from cattle on days 0, 7, 14, 21, and 28...
August 2, 2017: Foodborne Pathogens and Disease
https://www.readbyqxmd.com/read/28766825/beyond-the-bet-family-targeting-cbp-p300-with-4-acyl-pyrroles
#4
Martin Hügle, Xavier Lucas, Dmytro Ostrovskyi, Pierre Regenass, Stefan Gerhardt, Oliver Einsle, Mirjam Hau, Manfred Jung, Bernhard Breit, Stefan Günther, Daniel Wohlwend
BET bromodomain inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms, and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. Here, we introduce XDM-CBP, a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. In addition to X-ray crystal structure analysis and thermodynamic profiling, we used XDM-CBP in in vitro cell screenings of several cancer cell lines to study its inhibitory potential on cancer cell proliferation...
August 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28765013/structure-based-design-synthesis-and-in-vitro-antiproliferative-effects-studies-of-novel-dual-brd4-hdac-inhibitors
#5
Mingfeng Shao, Linhong He, Li Zheng, Lingxiao Huang, Yuanyuan Zhou, Taijing Wang, Yong Chen, Mingsheng Shen, Fang Wang, Zhuang Yang, Lijuan Chen
Histone acetylation marks play important roles in controlling gene expressions and are removed by histone deacetylases (HDACs). These marks are read by bromodomain and extra-terminal (BET) proteins, whose targeted inhibitors are under clinical investigation. BET and HDAC inhibitors have been demonstrated to be synergistically killing in Mycinduced murine lymphoma. Herein, we combine the inhibitory activities of BET and HDAC into one molecule through structure-based design method and evaluate its function. The majority of these synthesized compounds showed inhibitory activity against second bromdomains(BRD) of BRD4 and HDAC1...
July 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28747456/do-brd-4-s-of-a-feather-flock-together-how-an-inflammation-driven-epigenetic-regulator-may-link-pulmonary-hypertension-and-coronary-artery-disease
#6
EDITORIAL
Partha Dutta, Delphine Gomez, Mark T Gladwin
No abstract text is available yet for this article.
August 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28727052/rapid-communication-subclinical-bovine-respiratory-disease-loci-and-pathogens-associated-with-lung-lesions-in-feedlot-cattle
#7
J N Kiser, T E Lawrence, M Neupane, C M Seabury, J F Taylor, J E Womack, H L Neibergs
Bovine respiratory disease (BRD) is an economically important disease of feedlot cattle that is caused by viral and bacterial pathogen members of the BRD complex. Many cases of subclinical BRD go untreated and are not detected until slaughter, when lung lesions are identified. The objectives of this study were to identify which BRD pathogens were associated with the presence of lung lesions at harvest and to identify genomic loci that were associated with susceptibility to lung lesions as defined by consolidation of the lung and/or the presence of fibrin tissue...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28727007/best-management-practices-for-newly-weaned-calves-for-improved-health-and-well-being
#8
B K Wilson, C J Richards, D L Step, C R Krehbiel
Morbidity and mortality in newly weaned calves resulting from bovine respiratory disease (BRD) continue to be the most significant problems facing the beef industry. Morbidity attributed to BRD accounts for approximately 75% of total feedlot morbidity. Several experiments have documented the economic impacts of BRD. Direct costs attributable to BRD include death loss, treatment and labor costs, and prevention costs, while indirect costs associated with BRD include decreased growth performance and feed efficiency, increased days on feed, and decreased carcass merit and market value...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28714688/design-of-a-chemical-probe-for-the-bromodomain-and-plant-homeodomain-finger-containing-brpf-family-of-proteins
#9
Niall Igoe, Elliott D Bayle, Cynthia Tallant, Oleg Fedorov, Julia C Meier, Pavel Savitsky, Catherine Rogers, Yannick Morias, Sarah Scholze, Helen Boyd, Danen Cunoosamy, David M Andrews, Anne Cheasty, Paul E Brennan, Susanne Müller, Stefan Knapp, Paul V Fish
The bromodomain and PHD finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRD1 over BRPF3, whereas binding to BRD9 was weaker. 16 has excellent selectivity over non-class IV BRD proteins. Target engagement of BRPF1B and BRD1 with 16 was demonstrated in nanoBRET and FRAP assays...
July 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28706277/dna-binding-drives-the-association-of-brg1-hbrm-bromodomains-with-nucleosomes
#10
Emma A Morrison, Julio C Sanchez, Jehnna L Ronan, Daniel P Farrell, Katayoun Varzavand, Jenna K Johnson, Brian X Gu, Gerald R Crabtree, Catherine A Musselman
BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements...
July 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28705198/evaluation-of-a-multiplex-real-time-pcr-for-detection-of-four-bacterial-agents-commonly-associated-with-bovine-respiratory-disease-in-bronchoalveolar-lavage-fluid
#11
Henk J Wisselink, Jan B W J Cornelissen, Fimme J van der Wal, Engbert A Kooi, Miriam G Koene, Alex Bossers, Bregtje Smid, Freddy M de Bree, Adriaan F G Antonis
BACKGROUND: Pasteurella multocida, Mannheimia haemolytica, Histophilus somni and Trueperella pyogenes are four bacterial agents commonly associated with bovine respiratory disease (BRD). In this study a bacterial multiplex real-time PCR (the RespoCheck PCR) was evaluated for the detection in bronchoalveolar lavage fluid (BALF) of these four bacterial agents. RESULTS: The analytical sensitivity of the multiplex real-time PCR assay determined on purified DNA and on bacterial cells of the four target pathogens was one to ten fg DNA/assay and 4 × 10(-1) to 2 × 10(0) CFU/assay...
July 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28667417/enhanced-biomass-and-oxidative-stress-tolerance-of-synechococcus-elongatus-pcc-7942-overexpressing-the-dhar-gene-from-brassica-juncea
#12
Young-Saeng Kim, Il-Sup Kim, Joseph S Boyd, Arnaud Taton, James W Golden, Ho-Sung Yoon
OBJECTIVES: To improve the oxidative stress tolerance, biomass yield, and ascorbate/dehydroascorbate (AsA/DHA) ratio of Synechococcus elongatus PCC 7942 in the presence of H2O2, by heterologous expression of the dehydroascorbate reductase (DHAR) gene from Brassica juncea (BrDHAR). RESULTS: Under H2O2 stress, overexpression of BrDHAR in the transgenic strain (BrD) of S. elongatus greatly increased the AsA/DHA ratio. As part of the AsA recycling system, the oxidative stress response induced by reactive oxygen species was enhanced, and intracellular H2O2 level decreased...
June 30, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28630323/role-of-the-cbp-catalytic-core-in-intramolecular-sumoylation-and-control-of-histone-h3-acetylation
#13
Sangho Park, Robyn L Stanfield, Maria A Martinez-Yamout, H Jane Dyson, Ian A Wilson, Peter E Wright
The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28624514/bromodomain-containing-proteins-in-prostate-cancer
#14
REVIEW
Alfonso Urbanucci, Ian G Mills
Several oncogenic factors have been involved in prostate cancer progression. However, therapeutic approaches still focus on suppression of androgen receptor (AR) signaling. In fact, whereas the full-length AR incorporates a ligand-binding domain, which has become a drug target for competitive inhibitors, other transcription factors often do not have tractable binding pockets that aid drug development. Consequently drug development efforts have turned to transcription co-regulators, often chromatin-modifying enzymes or factors that bind to epigenetic modifications to chromatin...
June 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28619153/identification-of-candidate-protein-markers-of-bovine-parainfluenza-virus-type-3-infection-using-an-in-vitro-model
#15
Darren W Gray, Michael D Welsh, Simon Doherty, Mark H Mooney
Bovine Parainfluenza Virus Type 3 (BPI3V) infections are often asymptomatic, causing respiratory tissue damage and immunosuppression, predisposing animals to severe bacterial pneumonia, the leading cause of Bovine Respiratory Disease (BRD) mortality. As with many pathogens, routine BPI3V serology does not indicate the presence of damaged respiratory tissue or active infection. In vitro proteomic marker screening using disease relevant cell models could help identify markers of infection and tissue damage that are also detectable during in vivo infections...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28615070/a-randomised-clinical-trial-of-a-metaphylactic-treatment-with-tildipirosin-for-bovine-respiratory-disease-in-veal-calves
#16
J Berman, D Francoz, J Dubuc, S Buczinski
BACKGROUND: Bovine respiratory disease (BRD) is a major problem in veal calf rearing units. The objective of this randomised clinical trial was to assess the effectiveness of tildipirosin as a metaphylactic treatment in veal calves on the number of BRD treatments, lung consolidation on thoracic ultrasonography (TUS) and average daily gain (ADG). A total of 209 veal calves from a pre-weaning fattening unit were randomly allocated to receive one of two treatments (tildipirosin 4 mg/kg, subcutaneously, n = 109; placebo 0...
June 14, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28602021/evaluation-of-mollicutes-microorganisms-in-respiratory-disease-of-cattle-and-their-relationship-to-clinical-signs
#17
G Tortorelli, N Carrillo Gaeta, B L Mendonça Ribeiro, L Miranda Marques, J Timenetsky, L Gregory
BACKGROUND: Bovine respiratory disease (BRD) is an important problem in cattle production that is responsible for economic losses in dairy herds. Mycoplasma spp. are described as an important etiological agent of BRD. HYPOTHESIS: To evaluate the occurrence of the most important mycoplasmas in the lower respiratory tract of healthy and BRD cattle in relationship to clinical signs of BRD. ANIMALS: Sixty young dairy cattle were classified as healthy (n = 32) or cattle showing clinical signs of BRD (n = 28)...
July 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28592170/current-options-to-manage-waldenstr%C3%A3-m-s-macroglobulinemia
#18
Giulia Benevolo, Maura Nicolosi, Elisa Santambrogio, Umberto Vitolo
Waldenström's macroglobulinemia (WM) is a rare, incurable B-cell lymphoma, with a median survival of 5-10 years in symptomatic patients. There is no consensus on the standard of care and several agents are currently used in these patients. Areas covered: In this article, we will review the use of standard therapies and new drugs investigated such as monoclonal antibodies, proteasome inhibitors, immunomodulatory agents, Bruton's tyrosine kinase inhibitors and novel agents in early-stage development. Expert commentary: RCD (Rituximab/Cyclophosphamide/Dexamethasone) is an effective and safe treatment in first line in WM...
June 19, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28591577/androgen-receptor-deregulation-drives-bromodomain-mediated-chromatin-alterations-in-prostate-cancer
#19
Alfonso Urbanucci, Stefan J Barfeld, Ville Kytölä, Harri M Itkonen, Ilsa M Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R Jeffrey Karnes, Ashley E Ross, Edward M Schaeffer, Donald J Vander Griend, Stefan Knapp, Eva Corey, Felix Y Feng, Peter S Nelson, Fahri Saatcioglu, Karen E Knudsen, Teuvo L J Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G Mills
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28541716/investigational-bet-bromodomain-protein-inhibitors-in-early-stage-clinical-trials-for-acute-myelogenous-leukemia-aml
#20
REVIEW
Thorsten Braun, Claude Gardin
Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials...
July 2017: Expert Opinion on Investigational Drugs
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