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https://www.readbyqxmd.com/read/28300771/inhibitors-of-brd4-protein-from-a-marine-derived-fungus-alternaria-sp-nh-f6
#1
Hui Ding, Dashan Zhang, Biao Zhou, Zhongjun Ma
Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein-protein interaction inhibitors have the potential to modulate multiple diseases by their profound anti-inflammatory and antiproliferative effects. In order to explore new BRD4 inhibitors as well as lead compounds for the development of new drugs, the secondary metabolites of Alternaria sp...
March 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28295570/agreement-among-4-sampling-methods-to-identify-respiratory-pathogens-in-dairy-calves-with-acute-bovine-respiratory-disease
#2
D Doyle, B Credille, T W Lehenbauer, R Berghaus, S S Aly, J Champagne, P Blanchard, B Crossley, L Berghaus, S Cochran, A Woolums
BACKGROUND: Four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (BRD): the nasal swab (NS), guarded nasopharyngeal swab (NPS), bronchoalveolar lavage (BAL), and transtracheal wash (TTW). Agreement among these methods has not been well characterized. OBJECTIVE: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD...
March 14, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28282443/the-bovine-paranasal-sinuses-bacterial-flora-epithelial-expression-of-nitric-oxide-and-potential-role-in-the-in-herd-persistence-of-respiratory-disease-pathogens
#3
Gerard M Murray, Rónan G O'Neill, Alison M Lee, Máire C McElroy, Simon J More, Aisling Monagle, Bernadette Earley, Joseph P Cassidy
The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3)...
2017: PloS One
https://www.readbyqxmd.com/read/28265460/thoracoscopy-as-a-safe-and-effective-technique-for-exploring-calves-affected-with-bovine-respiratory-disease
#4
Natividad Perez-Villalobos, Iñaki Espinosa-Crespo, José Sampayo-Cabrera, Juan-Vicente González-Martín, Antonio Gonzalez-Bulnes, Susana Astiz
BACKGROUND: Bovine respiratory disease (BRD) is one of the leading causes of economic losses in the beef and dairy industry. Reliable antemortem tools for diagnosing BRD would improve the efficacy of treatment and reduce costs. Here we examined whether the relatively simple technique of thoracoscopy can support BRD diagnosis under field conditions. We also compared various equipment set-ups in order to optimize the safety and efficacy of the procedure. A total of 24 thoracoscopic procedures were performed in 17 calves diagnosed with BRD and in 2 healthy control calves...
2017: Journal of Animal Science and Technology
https://www.readbyqxmd.com/read/28265070/bet-n-terminal-bromodomain-inhibition-selectively-blocks-th17-cell-differentiation-and-ameliorates-colitis-in-mice
#5
Kalung Cheung, Geming Lu, Rajal Sharma, Adam Vincek, Ruihua Zhang, Alexander N Plotnikov, Fan Zhang, Qiang Zhang, Ying Ju, Yuan Hu, Li Zhao, Xinye Han, Jamel Meslamani, Feihong Xu, Anbalagan Jaganathan, Tong Shen, Hongfa Zhu, Elena Rusinova, Lei Zeng, Jiachi Zhou, Jianjun Yang, Liang Peng, Michael Ohlmeyer, Martin J Walsh, David Y Zhang, Huabao Xiong, Ming-Ming Zhou
T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4(+) T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28240958/comparison-of-the-diagnostic-performance-of-bacterial-culture-of-nasopharyngeal-swab-and-bronchoalveolar-lavage-fluid-samples-obtained-from-calves-with-bovine-respiratory-disease
#6
Sarah F Capik, Brad J White, Brian V Lubbers, Michael D Apley, Keith D DeDonder, Robert L Larson, Greg P Harhay, Carol G Chitko-McKown, Dayna M Harhay, Ted S Kalbfleisch, Gennie Schuller, Michael L Clawson
OBJECTIVE To compare predictive values, extent of agreement, and gamithromycin susceptibility between bacterial culture results of nasopharyngeal swab (NPS) and bronchoalveolar lavage fluid (BALF) samples obtained from calves with bovine respiratory disease (BRD). ANIMALS 28 beef calves with clinical BRD. PROCEDURES Pooled bilateral NPS samples and BALF samples were obtained for bacterial culture from calves immediately before and at various times during the 5 days after gamithromycin (6 mg/kg, SC, once) administration...
March 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28231472/effects-of-nasal-instillation-of-a-nitric-oxide-releasing-solution-or-parenteral-administration-of-tilmicosin-on-the-nasopharyngeal-microbiota-of-beef-feedlot-cattle-at-high-risk-of-developing-respiratory-tract-disease
#7
E Timsit, M Workentine, T Crepieux, C Miller, G Regev-Shoshani, A Schaefer, T Alexander
Nitric oxide has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as inferior to a parenteral injection of tilmicosin (macrolide antibiotic) for control of bovine respiratory disease (BRD) in cattle at high-risk of developing BRD. We hypothesized that this inferiority was due to differences between treatments with regards to their effects on the nasopharyngeal microbiota. The objective was to compare nasal instillation of NORS versus parenteral administration of tilmicosin regarding their effects on the nasopharyngeal microbiota of feedlot cattle at high-risk of developing BRD...
February 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28209615/targeted-degradation-of-bet-proteins-in-triple-negative-breast-cancer
#8
Longchuan Bai, Bing Zhou, Chao-Yie Yang, Jiao Ji, Donna McEachern, Sally Przybranowski, Hui Jiang, Jiantao Hu, Fuming Xu, Yujun Zhao, Liu Liu, Ester Fernandez-Salas, Jing Xu, Yali Dou, Bo Wen, Duxin Sun, Jennifer L Meagher, Jeanne Stuckey, Daniel F Hayes, Shunqiang Li, Matthew J Ellis, Shaomeng Wang
Triple-negative breast cancers (TNBC) remain clinically challenging with a lack of options for targeted therapy. In this study, we report the development of a second-generation BET bromodomain (BRD) inhibitor, BETd-246, which exhibits superior selectivity, potency and antitumor activity. In human TNBC cells, BETd-246 induced degradation of BET transcription factors at low nanomolar concentrations within 1 hr of exposure, resulting in robust growth inhibition and apoptosis. BETd-246 was more potent and effective in TNBC cells than its parental BET inhibitor compound BETi-211...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28110784/an-inactivated-influenza-d-virus-vaccine-partially-protects-cattle-from-respiratory-disease-caused-by-homologous-challenge
#9
Ben M Hause, Lucas Huntimer, Shollie Falkenberg, Jamie Henningson, Kelly Lechtenberg, Tom Halbur
Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine respiratory disease (BRD), we sought to investigate the efficacy of an inactivated IDV vaccine. Vaccinated calves seroconverted with hemagglutination inhibition titers 137-169 following two doses. Non-vaccinated calves challenged with a homologous virus exhibited signs of mild respiratory disease from days four to ten post challenge which was significantly different than negative controls at days five and nine post challenge...
February 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28093111/efficacy-of-tildipirosin-metaphylaxis-for-the-prevention-of-respiratory-disease-otitis-and-mortality-in-pre-weaned-holstein-calves
#10
A G V Teixeira, J A A McArt, R C Bicalho
The aim of this study was to evaluate the efficacy of two metaphylactic approaches (long acting antibiotic injected once at 10 days of life or twice at 10 and 35 days of life) on the prevention of bovine respiratory disease (BRD), otitis and mortality in high-risk group-housed pre-weaned Holstein heifer calves. The antibiotic of choice for the metaphylactic approach was a long acting macrolide (tildipirosin) administered subcutaneously at the base of the neck at a dose of 1 mL per 45 kg body weight. A clinical trial was carried out on one dairy farm with random allocation of newborn calves to one of three treatments: (1) control (CTR); (2) one injection at 10 days of life (M1); and (3) two injections at 10 and 35 days of life (M2)...
January 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28074713/pathogens-patterns-of-pneumonia-and-epidemiologic-risk-factors-associated-with-respiratory-disease-in-recently-weaned-cattle-in-ireland
#11
Gerard M Murray, Simon J More, Dónal Sammin, Mìcheàl J Casey, Máire C McElroy, Rónan G O'Neill, William J Byrne, Bernadette Earley, Tracy A Clegg, Hywel Ball, Colin J Bell, Joseph P Cassidy
We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently...
January 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28068087/design-of-a-biased-potent-small-molecule-inhibitor-of-the-bromodomain-and-phd-finger-containing-brpf-proteins-suitable-for-cellular-and-in-vivo-studies
#12
Niall Igoe, Elliott D Bayle, Oleg Fedorov, Cynthia Tallant, Pavel Savitsky, Catherine Rogers, Dafydd R Owen, Gauri Deb, Tim C P Somervaille, David M Andrews, Neil Jones, Anne Cheasty, Hamish Ryder, Paul E Brennan, Susanne Müller, Stefan Knapp, Paul V Fish
The BRPF (bromodomain and PHD finger-containing) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Evaluation of the BRPF family as a potential drug target is at an early stage although there is an emerging understanding of a role in acute myeloid leukemia (AML). We report the optimization of fragment hit 5b to 13-d as a biased, potent inhibitor of the BRD of the BRPFs with excellent selectivity over nonclass IV BRD proteins. Evaluation of 13-d in a panel of cancer cell lines showed a selective inhibition of proliferation of a subset of AML lines...
January 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28064409/assessment-of-nebulisation-of-sodium-ceftiofur-in-the-treatment-of-calves-naturally-infected-with-bovine-respiratory-disease
#13
Vivek Joshi, V K Gupta, U Dimri, O R Vinodh Kumar, D K Sharma, A G Bhanuprakash
Twelve screened cases of bovine respiratory disease (BRD) in calves were enrolled. Six of the calves were treated intramuscularly with sodium ceftiofur (1 mg/kg), and six were treated with nebulised sodium ceftiofur (1 mg/kg). Comparative evaluation of the two therapeutic modalities was based on repetitive analysis of hematological profile of calves on days 0, 5, and 10 post-therapy. The mortality rate in the group of calves treated with the nebulised sodium ceftiofur was significantly (p < 0.001) lower, and their clinical and hematological parameters returned to normal significantly (p < 0...
March 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28058252/risk-assessment-in-the-recovery-of-food-for-social-solidarity-purposes-preliminary-data
#14
Vesna Milicevic, Giampaolo Colavita, Marta Castrica, Sabrina Ratti, Antonella Baldi, Claudia M Balzaretti
The most recent study, conducted by Politecnico of Milan, on food surplus management in Italy shows that in the Italian food supply chain the food surplus is around 5.5 million tons/year, and the amount of food wasted is around 5.1 million tons/year. During 2015, the charitable organizations (COs) belonging to the Italian Food Bank Network, active in recovering and distributing food for social solidarity's purposes, reused 381,345 tons of food from 2292 donors. The main supplying sources of the Banco Alimentare Network are: food industries, organized large-scale retail trade and collective catering service...
September 20, 2016: Italian Journal of Food Safety
https://www.readbyqxmd.com/read/28053347/functions-of-bromodomain-containing-proteins-and-their-roles-in-homeostasis-and-cancer
#15
REVIEW
Takao Fujisawa, Panagis Filippakopoulos
Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues - particularly in histones - and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves...
April 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28046137/rapid-communication-variance-component-estimates-for-charolais-sired-fed-cattle-and-relative-economic-impact-of-bovine-respiratory-disease
#16
J W Buchanan, M D MacNeil, R C Raymond, A R McClain, A L Van Eenennaam
Variance components were estimated and relative economic importance of bovine respiratory disease (BRD) was derived from 3 yr of performance, morbidity, and mortality data collected from a single beef cattle finishing operation. One thousand one hundred eighty nine of 12,812 Charolais-sired calves were treated for BRD during the finishing period. Weaning weight (WW), DMI, days to harvest (D2H), HCW, yield grade (YG), and marbling score determined by image analysis (MARB) were collected to quantify the economic impact associated with treatment for BRD...
December 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/28032455/in-silico-design-and-bioevaluation-of-selective-benzotriazepine-brd4-inhibitors-with-potent-antiosteoclastogenic-activity
#17
Vishwa Deepak, Binglin Wang, Dwayne Koot, Abe Kasonga, Xiao Xing Stander, Magdalena Coetzee, Andre Stander
The bromodomain (BRD) and extra-terminal domain (BET) protein family binds to acetylated histones on lysine residues and act as epigenetic readers. Recently, the role of this protein family in bone loss has been gaining attention. Earlier studies have reported that benzotriazepine (Bzt) derivatives could be effective inhibitors of BET proteins. In this study by using in silico tools we designed three Bzt analogs (W49, W51, and W52). By docking, molecular simulations and chemiluminescent alpha screen binding assay we show that the studied analogs were selective at inhibiting BRD4 when compared to BRD2...
December 29, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27988122/deciphering-upper-respiratory-tract-microbiota-complexity-in-healthy-calves-and-calves-that-develop-respiratory-disease-using-shotgun-metagenomics
#18
Natália C Gaeta, Svetlana F Lima, Andre G Teixeira, Erika K Ganda, Georgios Oikonomou, Lilian Gregory, Rodrigo C Bicalho
Bovine respiratory disease (BRD) is a multifactorial disorder responsible for severe economic losses in dairy and feedlot herds. Advances in next-generation sequencing mean that microbial communities in clinical samples, including non-culturable bacteria, can be characterized. Our aim was to evaluate the microbiota of the upper respiratory tract of healthy calves and calves with BRD using whole-genome sequencing (shotgun metagenomics). We performed deep nasopharyngeal swabs on 16 Holstein heifer calves (10 healthy and 6 diagnosed with BRD during the study) at 14 and 28 d of life in 1 dairy herd near Ithaca, New York...
February 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/27983764/bendamustine-lenalidomide-and-dexamethasone-brd-has-high-activity-as-2-nd-line-therapy-for-relapsed-and-refractory-multiple-myeloma-a-phase-ii-trial
#19
Ulrich J M Mey, Wolfram Brugger, Heike Schwarb, Stefanie Pederiva, Andreas Schwarzer, Tobias Dechow, Paul Jehner, Jacqueline Rauh, Christian J Taverna, Mathias Schmid, Martin Schmidt-Hieber, Steffen Doerfel, Natalie Fischer, Axel Ruefer, Carsten Ziske, Wolfgang Knauf, Richard Cathomas, Roger von Moos, Felicitas Hitz, Rafael Sauter, Elke Hiendlmeyer, Nathan Cantoni, Mario Bargetzi, Christoph Driessen
The combination of lenalidomide (Revlimid(®) , R) and dexamethasone (d) is a standard regimen for patients with relapsed/refractory multiple myeloma (rrMM). With this regimen, only a small fraction of patients will achieve high quality responses [≥ very good partial response (VGPR)]. The combination of bendamustine (B), lenalidomide and dexamethasone (BRd) has shown high efficacy in patients with advanced rrMM. However, dose-limiting haematotoxicity restricted its use in extensively pre-treated patient populations...
March 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27980108/dual-hdac-and-pi3k-inhibitor-cudc-907-downregulates-myc-and-suppresses-growth-of-myc-dependent-cancers
#20
Kaiming Sun, Ruzanna Atoyan, Mylissa A Borek, Steven Dellarocca, Maria Elena S Samson, Anna W Ma, Guang-Xin Xu, Troy Patterson, David P Tuck, Jaye L Viner, Ali Fattaey, Jing Wang
Upregulation of MYC is a common driver event in human cancers, and some tumors depend on MYC to maintain transcriptional programs that promote cell growth and proliferation. Preclinical studies have suggested that individually targeting upstream regulators of MYC, such as histone deacetylases (HDAC) and phosphoinositide 3-kinases (PI3K), can reduce MYC protein levels and suppress the growth of MYC-driven cancers. Synergy between HDAC and PI3K inhibition in inducing cancer cell death has also been reported, but the involvement of MYC regulation is unclear...
February 2017: Molecular Cancer Therapeutics
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