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https://www.readbyqxmd.com/read/29228881/unravelling-novel-congeners-from-acetyllysine-mimicking-ligand-targeting-a-lysine-acetyltransferase-pcaf-bromodomain
#1
Venkatesan Suryanarayanan, Sanjeev Kumar Singh
p300/CBP Associated Factor (PCAF) bromodomain (BRD), a lysine acetyltransferases, has emerged as a promising drug target as its dysfunction is linked to onset and progression of several diseases like cancer, diabetes, AIDS etc. In this study, a three featured E-Pharmacophore (ARR) was generated based on acetyllysine mimicking inhibitor of PCAF BRD which is available as co-crystal structure (PDB ID: 5FDZ). It was used for filtering small molecule databases followed by molecular docking and consequently validated using enrichment calculation...
December 11, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29206855/linking-disease-epidemiology-and-livestock-productivity-the-case-of-bovine-respiratory-disease-in-france
#2
Alexis Delabouglise, Andrew James, Jean-François Valarcher, Sara Hagglünd, Didier Raboisson, Jonathan Rushton
Concerns are growing over the impact of livestock farming on environment and public health. The livestock industry is faced with the double constraint of limiting its use of natural resources and antimicrobials while ensuring its economic sustainability. In this context, reliable methods are needed to evaluate the effect of the prevention of endemic animal diseases on the productivity of livestock production systems. In this study, an epidemiological and productivity model was used to link changes in Bovine Respiratory Disease (BRD) incidence with the productivity of the beef and dairy cattle sectors in France...
2017: PloS One
https://www.readbyqxmd.com/read/29197695/probing-numerical-laplace-inversion-methods-for-two-and-three-site-molecular-exchange-between-interconnected-pore-structures
#3
Emilia V Silletta, María B Franzoni, Gustavo A Monti, Rodolfo H Acosta
Two-dimension (2D) Nuclear Magnetic Resonance relaxometry experiments are a powerful tool extensively used to probe the interaction among different pore structures, mostly in inorganic systems. The analysis of the collected experimental data generally consists of a 2D numerical inversion of time-domain data where T2-T2 maps are generated. Through the years, different algorithms for the numerical inversion have been proposed. In this paper, two different algorithms for numerical inversion are tested and compared under different conditions of exchange dynamics; the method based on Butler-Reeds-Dawson (BRD) algorithm and the fast-iterative shrinkage-thresholding algorithm (FISTA) method...
November 30, 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/29189147/disrupting-acetyl-lysine-interactions-recent-advance-in-the-development-of-bet-inhibitors
#4
Fa Zhang, Shutao Ma
BACKGROUND: Histone acetylation is an essential way of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by Bromodomain-containing protein (BRD). In recent years, many researchers have found that a variety of malignancy, inflammatory and other diseases occurrence and development are associated with BRD4 expression disorders or dysfunction. Meanwhile, many the bromodomain inhibitors of the bromodomains and extra-terminal (BET) family is reported in many papers...
November 29, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29185614/permanent-pacing-after-transcatheter-aortic-valve-implantation-incidence-predictors-and-evolution-of-left-ventricular-function
#5
Cláudio Monteiro, Andres Di Leoni Ferrari, Paulo Ricardo Avancini Caramori, Luiz Antonio Ferreira Carvalho, Dimytri Alexandre de Alvim Siqueira, Luiz Eduardo Koenig São Thiago, Marco Perin, Valter C de Lima, Enio Guérios, Fabio Sandoli De Brito
BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a well-established procedure; however, atrioventricular block requiring permanent pacemaker implantation (PPI) is a common complication. OBJECTIVES: To determine the incidence, predictors and clinical outcomes of PPI after TAVI, focusing on how PPI affects left ventricular ejection fraction (LVEF) after TAVI. METHODS: The Brazilian Multicenter TAVI Registry included 819 patients submitted to TAVI due to severe aortic stenosis from 22 centers from January/2008 to January/2015...
November 27, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/29180474/vitamin-c-sensitizes-melanoma-to-bet-inhibitors
#6
Gaofeng Wang, Sushmita Mustafi, Vladimir Camarena, Claude-Henry Volmar, Tyler C Huff, David W Sant, Shaun P Brothers, Zhao-Jun Liu, Claes Wahlestedt
Bromodomain and extra-terminal inhibitors (BETi) are promising cancer therapies, yet prominent side effects of BETi at effective doses have been reported in Phase I clinical trials. Here we screened a panel of small molecules targeting epigenetic modulators against human metastatic melanoma cells. Cells were pretreated with or without ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity to drugs. Top hits were structurally unrelated BETi including JQ1, I-BET151, CPI-203, and BI-2536...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29170739/market-impacts-of-reducing-the-prevalence-of-bovine-respiratory-disease-in-united-states-beef-cattle-feedlots
#7
Kamina Keiko Johnson, Dustin L Pendell
Bovine respiratory disease (BRD) is a common endemic disease among North American feedlot cattle. BRD can lead to significant economic losses for individual beef cattle feedlot producers through mortality and morbidity. With promising new management and technology research that could reduce BRD prevalence, this study evaluates the potential impacts of a reduction of BRD in the US beef cattle feedlot sector. Using a multi-market, multi-commodity partial equilibrium economic model of the US agricultural industry, we evaluate the market impacts of reduced BRD to producers from various livestock, meat, and feedstuffs industries...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29166709/-effects-of-dexmedetomidine-on-myocardium-of-rats-with-severe-burn-at-early-stage
#8
D Wang, P L Yang, X Zhang, Y Liu
Objective: To investigate the effects of dexmedetomidine on myocardium of rats at early stage after severe burn. Methods: Twenty specific pathogen free male SD rats were immersed in 90 ℃ hot water for 20 s, causing 30% total body surface area (TBSA) full-thickness scald (hereafter referred to as burn) on the back. And then they were divided into burn resuscitation group (BR) and burn resuscitation+ dexmedetomidine group (BRD) according to the random number table, with 10 rats in each group. Sodium lactate Ringer's solution (2 mL·kg(-1)·%TBSA(-1)) were intraperitoneally injected into rats of both groups after burn...
November 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29150614/spatial-regulation-of-contractility-by-neuralized-and-bearded-during-furrow-invagination-in-drosophila
#9
Gantas Perez-Mockus, Khalil Mazouni, Vanessa Roca, Giulia Corradi, Vito Conte, François Schweisguth
Embryo-scale morphogenesis arises from patterned mechanical forces. During Drosophila gastrulation, actomyosin contractility drives apical constriction in ventral cells, leading to furrow formation and mesoderm invagination. It remains unclear whether and how mechanical properties of the ectoderm influence this process. Here, we show that Neuralized (Neur), an E3 ubiquitin ligase active in the mesoderm, regulates collective apical constriction and furrow formation. Conversely, the Bearded (Brd) proteins antagonize maternal Neur and lower medial-apical contractility in the ectoderm: in Brd-mutant embryos, the ventral furrow invaginates properly but rapidly unfolds as medial MyoII levels increase in the ectoderm...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29148850/atad2-in-cancer-a-pharmacologically-challenging-but-tractable-target
#10
Muzammal Hussain, Yang Zhou, Yu Song, H M Adnan Hameed, Hao Jiang, Yaoquan Tu, Jiancun Zhang
ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2's bromodomain (BRD) may be a very challenging task. ATAD2's BRD has been predicted as a "difficult to drug" or "least druggable" target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29143492/molecular-epidemiological-survey-and-phylogenetic-analysis-of-bovine-influenza-d-virus-in-japan
#11
H Mekata, M Yamamoto, S Hamabe, H Tanaka, T Omatsu, T Mizutani, B M Hause, T Okabayashi
The influenza D virus, a new member of the Orthomyxoviridae family, is predominantly found in cattle. Although viral pathology and clinical disease in cattle appear mild, this virus plays an important role as a trigger of bovine respiratory disease (BRD). BRD is a costly illness worldwide. Thus, epidemiological surveys of the influenza D virus are necessary. Here, we conducted a molecular epidemiological survey for the influenza D virus in healthy and respiratory-diseased cattle in Japan. We found that 2.1% (8/377) of the cattle were infected with influenza D...
November 16, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29113796/the-bet-brd-inhibitor-jq1-attenuates-diabetes-induced-cognitive-impairment-in-rats-by-targeting-nox4-nrf2-redox-imbalance
#12
Ershun Liang, Min Ma, Lei Wang, Xue Liu, Jinfeng Xu, Mingxiang Zhang, Ruixue Yang, Yuxia Zhao
Diabetes-induced oxidative damage is believed to play an important role in the development of cognitive dysfunction. In this study, the involvement of the Nox4-Nrf2 redox imbalance was investigated. STZ-induced diabetic rats exhibited obvious oxidative stress and apoptosis in the hippocampus assessed by augmentation of lipid peroxidation, positive TUNEL staining, elevated ratio of Bax/Bcl-2 and increased caspase 3 activity. Furthermore, hyperglycemia markedly increased Nox4 activity and reduced the activation of Nrf2 by suppressing its up-stream regulatory Akt as well as down-stream target HO-1...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29105570/molecular-survey-of-infectious-agents-associated-with-bovine-respiratory-disease-in-a-beef-cattle-feedlot-in-southern-brazil
#13
Selwyn A Headley, Werner Okano, Luciana C Balbo, Rogério A Marcasso, Thalita E Oliveira, Alice F Alfieri, Luiz C Negri Filho, Mariana Z Michelazzo, Silvio C Rodrigues, Anderson L Baptista, João Paulo E Saut, Amauri A Alfieri
We investigated the occurrence of infectious pathogens during an outbreak of bovine respiratory disease (BRD) in a beef cattle feedlot in southern Brazil that has a high risk of developing BRD. Nasopharyngeal swabs were randomly collected from steers ( n = 23) and assessed for the presence of infectious agents of BRD by PCR and/or RT-PCR assays. These included: Histophilus somni, Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCoV), bovine viral diarrhea virus (BVDV), bovine alphaherpesvirus 1 (BoHV-1), and bovine parainfluenza virus 3 (BPIV-3)...
November 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/29057951/preconditioning-with-far-infrared-irradiation-enhances-proliferation-cell-survival-and-migration-of-rat-bone-marrow-derived-stem-cells-via-cxcr4-erk-pathways
#14
Yun-Mi Jeong, Xian Wu Cheng, Sora Lee, Kyung Hye Lee, Haneul Cho, Jung Hee Kang, Weon Kim
Far-infrared radiation (FIR) has been shown to exert positive effects on the cardiovascular system. However, the biological effects of FIR on bone marrow-derived stem cells (BMSCs) are not understood. In the present study, BMSCs were isolated from rat femur bone marrow and cultured in vitro. To investigate the effects of an FIR generator with an energy flux of 0.13 mW/cm(2) on rat BMSCs, survival of BMSCs was measured by crystal violet staining, and cell proliferation was additionally measured using Ez-Cytox cell viability, EdU, and Brd U assays...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29056670/protein-composition-of-the-bovine-herpesvirus-1-1-virion
#15
Kaley A Barber, Hillary C Daugherty, Stephanie E Ander, Victoria A Jefferson, Leslie A Shack, Tibor Pechan, Bindu Nanduri, Florencia Meyer
Bovine herpesvirus (BoHV) type 1 is an important agricultural pathogen that infects cattle and other ruminants worldwide. Acute infection of the oro-respiratory tract leads to immune suppression and allows commensal bacteria to infect an otherwise healthy lower respiratory tract. This condition is known as the Bovine Respiratory Disease (BRD). BoHV-1 latently infects the host for life and periodical stress events re-initiate BRD, translating into high morbidity and large economic losses. To gain a better understanding of the biology of BoHV-1 and the disease it causes, we elucidated the protein composition of extracellular virions using liquid chromatography-mass spectrometry analysis...
February 20, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/29050361/bet-inhibitors-as-novel-therapeutic-agents-in-breast-cancer
#16
REVIEW
Alberto Ocaña, Cristina Nieto-Jiménez, Atanasio Pandiella
Tumoral cells not only depend on oncogenic abnormalities to maintain its malignant phenotype but on non-oncogenic vulnerabilities. Targeting epigenomics can modify specific cellular functions required for malignant transformation. The Bromodomain (BRD) family mediates their effect by recruiting proteins of the transcription machinery, recognizing acetylated-lysine residues in nucleosomal histones. Bromodomain and extra-terminal (BET) inhibitors have shown to produce growth inhibition in several tumors through the inhibition of the expression of several transcription factors...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29030520/combined-antibiotic-and-nsaid-offers-new-brd-treatment
#17
(no author information available yet)
No abstract text is available yet for this article.
October 14, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28982998/metagenomic-sequencing-of-bronchoalveolar-lavage-samples-from-feedlot-cattle-mortalities-associated-with-bovine-respiratory-disease
#18
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
https://www.readbyqxmd.com/read/28949335/the-bet-brd-inhibitor-jq1-improves-brain-plasticity-in-wt-and-app-mice
#19
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
https://www.readbyqxmd.com/read/28943305/targeting-the-cancer-epigenome-synergistic-therapy-with-bromodomain-inhibitors
#20
REVIEW
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
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