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Devin B Holman, Cassidy L Klima, Brenda J Ralston, Yan D Niu, Kim Stanford, Trevor W Alexander, Tim A McAllister
Bovine respiratory disease (BRD) is a significant and costly illness in feedlot cattle. Metagenomic analysis was performed on bronchoalveolar lavage samples obtained from 18 feedlot cattle that died of BRD.
October 5, 2017: Genome Announcements
E Benito, B Ramachandran, H Schroeder, G Schmidt, H Urbanke, S Burkhardt, V Capece, C Dean, A Fischer
Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease...
September 26, 2017: Translational Psychiatry
Mahalakshmi Ramadoss, Vijayalakshmi Mahadevan
Epigenetic and genomic alterations regulate the transcriptional landscape of cells during cancer onset and progression. Recent clinical studies targeting the epigenetic 'readers' (bromodomains) for cancer therapy have established the effectiveness of bromodomain (BRD) extraterminal (BET) inhibitors in treating several types of cancer. In this review, we discuss key mechanisms of BET inhibition and synergistic combinations of BET inhibitors with histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi), DNA methyltransferase inhibitors (DNMTi), kinase, B-cell lymphoma 2 (Bcl-2) and proteosome inhibitors, and immunomodulatory drugs for cancer therapy...
September 22, 2017: Drug Discovery Today
Guillaume Lhermie, Pierre-Louis Toutain, Farid El Garch, Alain Bousquet-Mélou, Sébastien Assié
The therapeutic efficacy of an early treatment protocol with an infection-stage adjusted fluoroquinolone regimen was evaluated in a field study on young bulls (YBs) presenting signs of bovine respiratory disease (BRD). A total of 195 YB (Charolais, Limousin, and Rouge-des-Prés breeds) from 6 farms implementing or not prophylactic antimicrobial treatments (PROPHY or absence) were randomly assigned to 1 of 2 experiment groups based on time of detection of BRD and first-line marbofloxacin regimen, early adjusted dose [Early 2 (E2)] or late standard dose [Late 10 (L10)]...
2017: Frontiers in Veterinary Science
Mohamed Zeineldin, James Lowe, Maria de Godoy, Nidia Maradiaga, Chelsey Ramirez, Mohamed Ghanem, Yassein Abd El-Raof, Brian Aldridge
Bovine respiratory disease (BRD) is one of the most serious causes of health and economic problems in the beef production industry, especially in recently weaned, intensely raised and newly transported feedlot cattle. While the importance of upper airway structure and function in the susceptibility of the lower respiratory tract to colonization with potential pathogens is well established, the role of the mucosal microbiota in respirtatory health is less well defined. The objective of this study was to characterize the nasopharyngeal microbiota of feedlot cattle at entry into a commercial feedlot, during initial management processing, and to compare the dynamics of change in these microbial communities between clinically healthy calves and those that develop BRD within the first month after entry...
September 2017: Veterinary Microbiology
Edouard Timsit, Jennyka Hallewell, Calvin Booker, Nicolas Tison, Samat Amat, Trevor W Alexander
Current information on prevalence and antimicrobial resistance (AMR) of bacterial respiratory pathogens is crucial to guide antimicrobial choice for control and treatment of bovine respiratory disease (BRD). The objectives were to describe the prevalence of three BRD-associated bacteria (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni) in the lower airways of feedlot cattle, and to analyze AMR in these bacteria. Cattle with (n=210) and without (n=107) BRD were sampled by trans-tracheal aspiration at four feedlots (Nov...
September 2017: Veterinary Microbiology
Mark A Hallen, Bruce R Donald
Motivation: When proteins mutate or bind to ligands, their backbones often move significantly, especially in loop regions. Computational protein design algorithms must model these motions in order to accurately optimize protein stability and binding affinity. However, methods for backbone conformational search in design have been much more limited than for sidechain conformational search. This is especially true for combinatorial protein design algorithms, which aim to search a large sequence space efficiently and thus cannot rely on temporal simulation of each candidate sequence...
July 15, 2017: Bioinformatics
Faten A M Abo-Aziza, Zaki A A
Background: In the field of cellular therapy, the impact of confluence degreeonharvesting or differentiation of BMMSCs and the effect of cell-to-cell contact remain controversial. Therefore, the effect of confluence on properties of BMMSCs was studied and efficiency of confluence-associated osteogenic differentiation was identified. Materials andMethods: The impact of 20, 50, 70, 80 and 100% confluences on proliferation properties of BMMSCs, expression of ERK and p-ERK proteins and glucose consumption rate was studied...
April 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
Sebastian Kostrhon, Georg Kontaxis, Tanja Kaufmann, Erika Schirghuber, Stefan Kubicek, Robert Konrat, Dea Slade
N-terminal histone tails are subject to many posttranslational modifications that are recognized by and interact with designated reader domains in histone-binding proteins. BROMO domain adjacent to zinc finger 2B (BAZ2B) is a multi-domain histone-binding protein that contains two histone reader modules, a plant homeodomain (PHD) and a bromodomain (BRD), linked by a largely disordered linker. While previous studies have reported a specificity of the PHD domain for the unmodified N-terminus of histone H3 and of the BRD domain for H3 acetylated at Lys-14 (H3K14ac), the exact mode of H3 binding by BAZ2B and its regulation are underexplored...
September 1, 2017: Journal of Biological Chemistry
Devan Griner, Caleb M Steffen, Kristopher M Day, Mark A Brzezienski
PURPOSE: Implant-based breast reconstruction is fraught with complications related to seroma formation. Soft tissue stabilization with progressive tension closure (PTC) has been shown to decrease seroma formation after various procedures but is less suitable for mastectomy flap stabilization. We evaluate the incidence of seroma in breast reconstruction using bioabsorbable barbed ribbon devices (BRDs) as a novel approach to PTC. METHODS: We performed a retrospective review of all patients whose mastectomy flaps were stabilized with BRDs...
August 29, 2017: Annals of Plastic Surgery
Aspen M Workman, Larry A Kuehn, Tara G McDaneld, Michael L Clawson, Carol G Chitko-McKown, John Dustin Loy
OBJECTIVE To evaluate the effect of serum antibody abundance against bovine coronavirus (BCV) on BCV shedding and risk of bovine respiratory disease (BRD) in beef calves from birth through the first 5 weeks in a feedlot. ANIMALS 890 natural-service crossbred beef calves from 4 research herds. PROCEDURES Serial blood samples for measurement of serum anti-BCV antibody abundance by an ELISA and nasal swab specimens for detection of BCV and other viral and bacterial BRD pathogens by real-time PCR methods were collected from all calves or subsets of calves at predetermined times from birth through the first 5 weeks after feedlot entry...
September 2017: American Journal of Veterinary Research
Keith Edward Baptiste, Niels Christian Kyvsgaard
A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications (prophylaxis, metaphylaxis) to healthy individuals. The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease (i.e. morbidity) and/or die (i.e. mortality). Bovine respiratory disease (BRD) represents the major indication for cattle antimicrobials worldwide. The objectives were to perform a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality...
September 29, 2017: Pathogens and Disease
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...
October 2017: Molecular Immunology
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
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...
October 2017: Foodborne Pathogens and Disease
Martin Hügle, Xavier Lucas, Dmytro Ostrovskyi, Pierre Regenass, Stefan Gerhardt, Oliver Einsle, Mirjam Hau, Manfred Jung, Bernhard Breit, Stefan Günther, Daniel Wohlwend
Bromodomain and extra-terminal domain (BET) 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. XDM-CBP is a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in screenings of several cancer cell lines in vitro to study its inhibitory potential on cancer cell proliferation...
October 2, 2017: Angewandte Chemie
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...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
Partha Dutta, Delphine Gomez, Mark T Gladwin
No abstract text is available yet for this article.
August 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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
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
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