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https://www.readbyqxmd.com/read/29244478/another-one-of-the-undruggable-targets-bites-the-dust-discovery-of-a-potent-and-selective-inhibitor-of-the-histone-acetyl-transferase-p300-cbp
#1
https://www.readbyqxmd.com/read/29243913/deep-red-amplified-spontaneous-emission-from-cis-configured-squaraine
#2
Hao Ye, Lin-Song Cui, Toshinori Matsushima, Chuanjiang Qin, Chihaya Adachi
We report deep-red amplified spontaneous emission (ASE) from cis-configured squaraine (cis-DCSQ1) under optical pumping. Doping of cis-DCSQ1 into a 4,4'-bis(9-carbazolyl)-2,2'-biphenyl (CBP) host film at an appropriate concentration (0.5 wt.% for this system) led to a marked increase of photoluminescence quantum yield because of efficient CBP-to-cis-DCSQ1 Förster resonance energy transfer and suppression of aggregation-caused quenching. Thus, this doped film showed clear ASE with a threshold of around 10 μJ cm-2 and peak wavelength of 687 nm...
December 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29240439/defining-metabolic-and-non-metabolic-regulation-of-histone-acetylation-by-a-nsaid-chemotype
#3
Jonathan Harold Shrimp, Julie Garlick, Tugsan Tezil, Alex W Sorum, Andrew J Worth, Ian Alexander Blair, Eric Verdin, Nathaniel W Snyder, Jordan L Meier
Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their effects on inflammatory gene expression. Although NSAIDs are known to impact multiple cellular signaling mechanisms, a recent finding is that the NSAID salicylate can disrupt histone acetylation, in part through direct inhibition of the lysine acetyltransferase (KAT) p300/CBP. While salicylate is a relatively weak KAT inhibitor, its CoA-linked metabolite is more potent; however, the ability of NSAID metabolites to inhibit KAT enzymes biochemically and in cells remains relatively unexplored...
December 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29239055/brain-structural-alterations-associated-with-dysfunctional-cognitive-control-of-pain-in-patients-with-low-back-pain
#4
O Chehadi, A C Rusu, K Konietzny, E Schulz, O Köster, T Schmidt-Wilcke, M I Hasenbring
BACKGROUND: Recent evidence has shown that chronic back pain (CBP) can lead to functional alterations in the circuitry underlying the cognitive control of pain. Thought suppression (TS) is a common type of cognitive control of pain. Previous research has shown that TS has paradoxical effects that may increase the awareness of pain. Pain-related TS may also increase individuals' attention to pain, which may also increase pain sensation, but thus far, the relationship between pain-related TS and structural brain alterations is unknown...
December 14, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29238435/primary-aldosteronism-with-type-2-diabetes-mellitus-requires-more-antihypertensive-drugs-for-blood-pressure-control-a-retrospective-observational-study
#5
Kennosuke Ohashi, Takeshi Hayashi, Yui Watanabe, Koichiro Hara, Rikako Ukichi, Hiroshi Asano, Hirofumi Suzuki, Kenji Yamashiro, Katsuyoshi Tojo, Masaya Sakamoto, Kazunori Utsunomiya
Background: Diabetes mellitus (DM) and primary aldosteronism (PA) have been reported to induce drug-resistant hypertension and atherosclerosis. It is likely that blood pressure (BP) control becomes far more difficult in PA patients with DM. However, precise clinical characteristics of PA with type 2 DM especially in the aspect of BP control are not clear. Methods: The study included 18 patients who were diagnosed as PA with DM and 52 PA patients without DM who matched age and sex and chosen as a control group...
January 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29234076/molecular-mechanism-of-k65-acetylation-induced-attenuation-of-ubc9-and-the-ndsm-interaction
#6
Mandar T Naik, Mooseok Kang, Chun-Chen Ho, Pei-Hsin Liao, Yung-Lin Hsieh, Nandita M Naik, Szu-Huan Wang, Iksoo Chang, Hsiu-Ming Shih, Tai-Huang Huang
The negatively charged amino acid-dependent sumoylation motif (NDSM) carries an additional stretch of acidic residues downstream of the consensus Ψ-K-x-E/D sumoylation motif. We have previously shown that acetylation of the SUMO E2 conjugase enzyme, Ubc9, at K65 downregulates its binding to the NDSM and renders a selective decrease in sumoylation of substrates with the NDSM motif. Here, we provide detailed structural, thermodynamic, and kinetics results of the interactions between Ubc9 and its K65 acetylated variant (Ac-Ubc9K65) with three NDSMs derived from Elk1, CBP, and Calpain2 to rationalize the mechanism beneath this reduced binding...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233896/retargeting-lentiviruses-via-spycatcher-spytag-chemistry-for-gene-delivery-into-specific-cell-types
#7
Nagarjun Kasaraneni, Ana M Chamoun-Emanuelli, Gus Wright, Zhilei Chen
We report a simple strategy for the creation of lentiviral vectors specific to any desired target cells. SpyTag is inserted into an engineered Sindbis virus envelope protein and displayed on the lentivirus surface to create Sindbis virus-SpyTag pseudoparticles (Sind-SpyTag-pp). The SpyTag serves as the covalent anchoring site for a target-cell-specific cell-binding protein (CBP) that is fused to a truncated SpyCatcher (SpyCatcherΔ). Target-cell-specific lentiviruses are created by mixing the Sind-SpyTag-pp and CBP-SpyCatcherΔ in vitro We first used a HER2-binding designed ankyrin repeat protein (DARPin...
December 12, 2017: MBio
https://www.readbyqxmd.com/read/29228881/unravelling-novel-congeners-from-acetyllysine-mimicking-ligand-targeting-a-lysine-acetyltransferase-pcaf-bromodomain
#8
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/29228599/chicken-bile-powder-protects-against-%C3%AE-naphthylisothiocyanate-induced-cholestatic-liver-injury-in-mice
#9
Yi-Fei Li, Jia-Sheng Wu, Yuan-Yuan Li, Yan Dai, Min Zheng, Jia-Kai Zeng, Guo-Feng Wang, Tian-Ming Wang, Wen-Kai Li, Xue-Yan Zhang, Ming Gu, Cheng Huang, Li Yang, Zheng-Tao Wang, Yue-Ming Ma
This study explored the effects of chicken bile powder (CBP), a 2000-year-old Chinese medicine, on α-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. CBP treatment for 14 days significantly ameliorated ANIT-induced changes in serum alanine aminotransferase, aspartate aminotransferase, bile acids, bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, and liver tissue morphology. Serum metabolomics showed changes in 24 metabolites in ANIT-exposed mice; 16 of these metabolites were reversed by CBP treatment via two main pathways (bile acid biosynthesis and arachidonic acid metabolism)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217654/the-p300-and-cbp-transcriptional-coactivators-are-required-for-beta-cell-and-alpha-cell-proliferation
#10
Chi Kin Wong, Adam K Wade-Vallance, Dan S Luciani, Paul K Brindle, Francis C Lynn, William T Gibson
p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone acetyltransferase activity. Various beta cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for beta cell function and health in vivo We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced alpha and beta cell area and islet insulin content...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29217191/tnf-%C3%AE-induces-expression-of-the-circadian-clock-gene-bmal1-via-dual-calcium-dependent-pathways-in-rheumatoid-synovial-cells
#11
Kohsuke Yoshida, Ayako Nakai, Kenta Kaneshiro, Naonori Hashimoto, Kohjin Suzuki, Koto Uchida, Teppei Hashimoto, Yoshiko Kawasaki, Koji Tateishi, Natsuko Nakagawa, Nao Shibanuma, Yoshitada Sakai, Akira Hashiramoto
Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca2+ chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29217140/inhibition-of-canonical-wnt-signaling-pathway-by-%C3%AE-catenin-cbp-inhibitor-icg-001-ameliorates-liver-fibrosis-in-vivo-through-suppression-of-stromal-cxcl12
#12
Büsra Öztürk Akcora, Gert Storm, Ruchi Bansal
Quiescent hepatic stellate cells (HSCs), in response to liver injury, undergo characteristic morphological transformation into proliferative, contractile and ECM-producing myofibroblasts. In this study, we investigated the implication of canonical Wnt signaling pathway in HSCs and liver fibrogenesis. Canonical Wnt signaling pathway activation and inhibition using β-catenin/CBP inhibitor ICG001 was examined in-vitro in TGFβ-activated 3T3, LX2, primary human HSCs, and in-vivo in CCl4-induced acute liver injury mouse model...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29213312/adding-tetrahydrofuran-to-dilute-acid-pretreatment-provides-new-insights-into-substrate-changes-that-greatly-enhance-biomass-deconstruction-by-clostridium-thermocellum-and-fungal-enzymes
#13
Vanessa A Thomas, Bryon S Donohoe, Mi Li, Yunqiao Pu, Arthur J Ragauskas, Rajeev Kumar, Thanh Yen Nguyen, Charles M Cai, Charles E Wyman
Background: Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29207655/egr-1-regulates-rta-transcription-through-a-cooperative-involvement-of-transcriptional-regulators
#14
Roni Sarkar, Subhash C Verma
Kaposi's sarcoma associated herpesvirus (KSHV) regulates the host cellular environment to establish life-long persistent infection by manipulating cellular signaling pathways, with approximately 1- 5% of cells undergoing lytic reactivation during the course of infection. Egr-1 (Early Growth Response Factor-1) is one such cellular transcription factor, which gets phosphorylated during the lytic phase of viral life cycle to perpetrate its function. This study demonstrates the mechanism of how Egr-1 mediates transcription of the immediate early gene, RTA (Replication and transcription activator), which is the lytic switch gene of KSHV...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205274/production-of-cellulosic-organic-acids-via-synthetic-fungal-consortia
#15
Scott A Scholz, Ian Graves, Jeremy J Minty, Xiaoxia Nina Lin
Consolidated bioprocessing is a potential breakthrough technology for reducing costs of biochemical production from lignocellulosic biomass. Production of cellulase enzymes, saccharification of lignocellulose and conversion of the resulting sugars into a chemical of interest occur simultaneously within a single bioreactor. In this study, synthetic fungal consortia composed of the cellulolytic fungus Trichoderma reesei and the production specialist Rhizopus delemar demonstrated conversion of microcrystalline cellulose (MCC) and alkaline pre-treated corn stover to fumaric acid in a fully consolidated manner without addition of cellulase enzymes or expensive supplements such as yeast extract...
December 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29203644/cited2-restrains-pro-inflammatory-macrophage-activation-and-response
#16
Gun-Dong Kim, Riku Das, Xiaoquan Rao, Jixin Zhong, Jeffrey A Deiuliis, Diana L Ramirez-Bergeron, Sanjay Rajagopalan, Ganapati H Mahabeleshwar
Macrophages are strategically distributed in mammalian tissues and play an essential role in priming immune response. However, macrophages need to constantly strike a balance between activation and inhibition state to avoid a futile inflammatory reaction. Herein, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage pro-inflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPARγ) activation and attendant select anti-inflammatory gene expression in macrophages...
December 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29202140/relation-of-the-polymorphism-of-cyp51a-sequence-and-the-susceptibility-of-aspergillus-fumigatus-isolates-to-triazoles-determined-by-commercial-gradient-test-etest-and-by-reference-methods
#17
Urszula Nawrot, Beata Sulik-Tyszka, Ewelina Kurzyk, Martyna Mroczyńska, Katarzyna Włodarczyk, Marta Wróblewska, Grzegorz Władysław Basak, Anna Brillowska-Dąbrowska
The aim of this study was to evaluate the accuracy of commercial gradient test (Etest) in the detection of triazole resistant Aspergillus fumigatus isolates using reference microdilution methods and the analysis of sequences of the cyp 51A gene. The study was performed on twenty clinical isolates which were identified as Aspergillus fumigatus based on the DNA sequences of the ITS1-2 fragment of ribosomal DNA and the β-tubulin gene, out of them seventeen isolates showed wild -type cyp51A sequence and three were positive for the mutation TR34/L98H...
November 30, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/29200657/reduction-of-progressive-thoracolumbar-adolescent-idiopathic-scoliosis-by-chiropractic-biophysics%C3%A2-cbp%C3%A2-mirror-image%C3%A2-methods-following-failed-traditional-chiropractic-treatment-a-case-report
#18
Joshua S Haggard, Jennifer B Haggard, Paul A Oakley, Deed E Harrison
[Purpose] To present a case demonstrating the reduction of progressive thoracolumbar scoliosis by incorporating Chiropractic BioPhysics® (CBP®) technique's mirror image® exercises, traction and blocking procedures based on the 'non-commutative properties of finite rotation angles under addition' engineering law. [Subject and Methods] A 15-year-old female presented with a right thoracolumbar scoliosis having a Cobb angle from T5-L3 of 27° and suffering from headaches and lower back pains. Her curve had progressed over the last two years despite being under traditional chiropractic care...
November 2017: Journal of Physical Therapy Science
https://www.readbyqxmd.com/read/29200656/nonsurgical-correction-of-straight-back-syndrome-thoracic-hypokyphosis-increased-lung-capacity-and-resolution-of-exertional-dyspnea-by-thoracic-hyperkyphosis-mirror-image%C3%A2-traction-a-cbp%C3%A2-case-report
#19
Jeffrey R Mitchell, Paul A Oakley, Deed E Harrison
[Purpose] To present the increase in thoracic kyphosis in a patient suffering from exertional dyspnea, reduced lung capacity, and spinal pains related to straight back syndrome (SBS). [Subject and Methods] A 33-year-old male patient was put on a CBP® corrective care program involving mirror image® traction procedures designed to increase the thoracic kyphosis. [Results] This patient had a 10° improvement in thoracic kyphosis in 16-weeks that was maintained 7-months later. There was a simultaneous reduction of pain, resolved exertional dyspnea, and a greater than 2 liter increase in lung capacity...
November 2017: Journal of Physical Therapy Science
https://www.readbyqxmd.com/read/29200655/lumbar-extension-traction-alleviates-symptoms-and-facilitates-healing-of-disc-herniation-sequestration-in-6-weeks-following-failed-treatment-from-three-previous-chiropractors-a-cbp%C3%A2-case-report-with-an-8%C3%A2-year-follow-up
#20
Paul A Oakley, Deed E Harrison
[Purpose] To present the outcome of a patient, having sciatica and MRI-verified disc herniation/sequestration who underwent Chiropractic BioPhysics® (CBP®) protocol designed to improve the lumbar lordosis. [Subject and Methods] A 56-year-old male suffered from chronic low back pain and recent sciatica due to lumbar disc herniation despite being under continuous care from three previous chiropractors. Radiographic analysis revealed a lumbar hypolordosis and MRI confirmed disc herniation and sequestration at L4-L5...
November 2017: Journal of Physical Therapy Science
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