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https://www.readbyqxmd.com/read/28822828/targeted-lowering-of-central-blood-pressure-in-patients-with-hypertension-baseline-recruitment-rationale-and-design-of-a-randomized-controlled-trial-the-low-cbp-study
#1
James E Sharman, Tony Stanton, Christopher M Reid, Anthony Keech, Philip Roberts-Thomson, Simon Stewart, Robert Greenough, Michael Stowasser, Walter P Abhayaratna
BACKGROUND: High blood pressure (BP) is the most common modifiable cause of death from cardiovascular disease. Lowering BP with medication improves patient outcomes, but even in populations with normal upper arm (brachial) BP there remains considerable residual risk for cardiovascular disease and this may be due to persistently elevated central BP. There has never been a trial to determine the value of targeted central BP lowering among patients with hypertension, and this was the aim of this study...
August 16, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28819026/therapeutic-targeting-of-the-cbp-p300-bromodomain-blocks%C3%A2-the-growth-of-castration-resistant-prostate-cancer
#2
Lingyan Jin, Jesse Garcia, Emily Chan, Cecile de la Cruz, Ehud Segal, Mark Merchant, Samir Kharbanda, Ryan Raisner, Peter M Haverty, Zora Modrusan, Justin Ly, Edna Choo, Susan Kaufman, Maureen H Beresini, F Anthony Romero, Steven Magnuson, Karen E Gascoigne
Resistance invariably develops to anti-androgen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here we report that the transcriptional co-activator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28816976/comparison-of-ambulatory-blood-pressure-and-clinic-blood-pressure-in-relation-to-cardiovascular-diseases-in-diabetic-patients
#3
Jian Shen, Zhi-Ming Li, Li-Zhen He, Ren-Sheng Deng, Jing-Guang Liu, Yuan-Sheng Shen
The aim of this study was to evaluate prognostic values of ambulatory blood pressure (ABP) and clinic blood pressure (CBP) in diabetic patients with hypertension. A total of 450 diabetic hypertensive patients without established cardiovascular diseases were enrolled and 416 patients who had finished 12months' follow-up were included in final analysis. Baseline data were collected and Cox proportional hazards regression analysis was used to evaluate prognostic value of ABP and CBP. Compared to those without study endpoints (n = 370), those experienced study endpoints (n = 46) were more elderly and more likely to be male, and had longer hypertension duration (7...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28815970/structural-insight-into-cbp-bromodomain-mediated-recognition-of-acetylated-histone-h3k56ac
#4
Li Xu, Aimin Cheng, Min Huang, Jiahai Zhang, Yiyang Jiang, Chongyuan Wang, Fudong Li, Hongyu Bao, Jia Gao, Na Wang, Jiuyang Liu, Jihui Wu, Catherine C L Wong, Ke Ruan
The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3-H4 dimers. CREB binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication-dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac, and thecontext in which such recognition occurs remains elusive...
August 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28810844/effect-of-tolvaptan-on-renal-handling-of-water-and-sodium-gfr-and-central-hemodynamics-in-autosomal-dominant-polycystic-kidney-disease-during-inhibition-of-the-nitric-oxide-system-a-randomized-placebo-controlled-double-blind-crossover-study
#5
Safa Al Therwani, My Emma Sofie Malmberg, Jeppe Bakkestroem Rosenbaek, Jesper Noergaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis. Nitric oxide (NO) stimulates natriuresis and diuresis, but its role is unknown during tolvaptan treatment in ADPKD. METHODS: Eighteen patients with ADPKD received tolvaptan 60 mg or placebo in a randomized, placebo-controlled, double blind, crossover study. L-NMMA (L-NG-monomethyl-arginine) was given as a bolus followed by continuous infusion during 60 min...
August 15, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28790157/sirt7-and-the-dead-box-helicase-ddx21-cooperate-to-resolve-genomic-r-loops-and-safeguard-genome-stability
#6
Chenlin Song, Agnes Hotz-Wagenblatt, Renate Voit, Ingrid Grummt
R loops are three-stranded nucleic acid structures consisting of an RNA:DNA heteroduplex and a "looped-out" nontemplate strand. As aberrant formation and persistence of R loops block transcription elongation and cause DNA damage, mechanisms that resolve R loops are essential for genome stability. Here we show that the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase DDX21 efficiently unwinds R loops and that depletion of DDX21 leads to accumulation of cellular R loops and DNA damage. Significantly, the activity of DDX21 is regulated by acetylation...
August 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28782640/effect-of-melatonin-on-neuronal-differentiation-requires-cbp-p300-mediated-acetylation-of-histone-h3-lysine-14
#7
Xian Li, Xueran Chen, Wenjuan Zhou, Shufang Ji, Xinyue Li, Guanchong Li, Guowei Liu, Fuwu Wang, Aijun Hao
The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties...
August 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28771326/in-plane-anisotropic-molecular-orientation-of-pentafluorene-and-its-application-to-linearly-polarized-electroluminescence
#8
Takeshi Komino, Hiroyuki Kuwae, Akiko Okada, Weixin Fu, Jun Mizuno, Jean-Charles Ribierre, Yuji Oki, Chihaya Adachi
By preparing parallelly aligned 1.9-μm-high SiO2 microfluidic channels on an indium tin oxide substrate surface, the solution flow direction during spin-coating was controlled to be parallel to the grating. Using this technique, a pentafluorene-4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) binary solution in chloroform was spin-coated to embed a 40-50 nm-thick 10 wt %-pentafluorene:CBP thin film in the channels. In-plane polarized photoluminescence measurements revealed that the pentafluorene molecules tended to orient along the grating, demonstrating that one-dimensional fluid flow can control the in-plane molecular orientation...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28768874/pgc1%C3%AE-transcriptional-adaptor-function-governs-hepatitis-b-virus-replication-by-controlling-hbcag-p21-protein-mediated-capsid-formation
#9
Rasha E Shalaby, Saira Iram, Bülent Çakal, Claudia E Oropeza, Alan McLachlan
In the human hepatoma cell line, Huh7, co-expression of the coactivators, peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), cAMP responsive element binding protein binding protein (CBP), steroid receptor coactivator 1 (SRC1) and protein arginine methyltransferase 1 (PRMT1) only modestly increase HBV biosynthesis. However, utilizing the human embryonic kidney cell line, HEK293T, it was possible to demonstrate that PGC1α alone can support viral biosynthesis independently of additional coactivator or transcription factor expression...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28766992/lactobacillus-fermentum-3872-as-a-potential-tool-for-combatting-campylobacter-jejuni-infections
#10
B Lehri, A M Seddon, A V Karlyshev
Due to the global spread of multidrug resistant pathogenic bacteria, alternative approaches in combating infectious diseases are required. One such approach is the use of probiotics. Lactobacillus fermentum 3872 is a promising probiotic bacterium producing a range of antimicrobial compounds, such as hydrogen peroxide and lactic acid. In addition, previous studies involving genome sequencing and analysis of L. fermentum 3872 allowed the identification of a gene encoding a cell surface protein referred to as collagen binding protein (CBP) not found in other strains of the species (according to the GenBank database), consisting of a C-terminal cell wall anchor domain (LPXT), multiple repeats of 'B domains' that form stalks presenting an 'A domain' required for adhesion...
August 2, 2017: Virulence
https://www.readbyqxmd.com/read/28766825/beyond-the-bet-family-targeting-cbp-p300-with-4-acyl-pyrroles
#11
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/28760417/cellodextrin-phosphorylase-from-ruminiclostridium-thermocellum-x-ray-crystal-structure-and-substrate-specificity-analysis
#12
Ellis C O'Neill, Giulia Pergolizzi, Clare E M Stevenson, David M Lawson, Sergey A Nepogodiev, Robert A Field
The GH94 glycoside hydrolase cellodextrin phosphorylase (CDP, EC 2.4.1.49) produces cellodextrin oligomers from short β-1→4-glucans and α-D-glucose 1-phosphate. Compared to cellobiose phosphorylase (CBP), which produces cellobiose from glucose and α-D-glucose 1-phosphate, CDP is biochemically less well characterised. Herein, we investigate the donor and acceptor substrate specificity of recombinant CDP from Ruminiclostridium thermocellum and we isolate and characterise a glucosamine addition product to the cellobiose acceptor with the non-natural donor α-D-glucosamine 1-phosphate...
July 21, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28755637/construction-of-a-ratiometric-fluorescent-probe-with-an-extremely-large-emission-shift-for-imaging-hypochlorite-in-living-cells
#13
Xuezhen Song, Baoli Dong, Xiuqi Kong, Chao Wang, Nan Zhang, Weiying Lin
Hypochlorite is one of the important reactive oxygen species (ROS) and plays critical roles in many biologically vital processes. Herein, we present a unique ratiometric fluorescent probe (CBP) with an extremely large emission shift for detecting hypochlorite in living cells. Utilizing positively charged α,β-unsaturated carbonyl group as the reaction site, the probe CBP itself exhibited near-infrared (NIR) fluorescence at 662nm, and can display strong blue fluorescence at 456nm when responded to hypochlorite...
July 12, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28752224/early-preclinical-changes-in-hippocampal-creb-binding-protein-expression-in-a-mouse-model-of-familial-alzheimer-s-disease
#14
Miren Ettcheto, Sonia Abad, Dmitry Petrov, Ignacio Pedrós, Oriol Busquets, Elena Sánchez-López, Gemma Casadesús, Carlos Beas-Zarate, Eva Carro, Carme Auladell, Jordi Olloquequi, Merce Pallàs, Jaume Folch, Antoni Camins
The molecular basis of memory loss in Alzheimer's disease (AD), the main cause of senile dementia, is under investigation. In the present study, we have focused on the early hippocampal memory-related changes in APPswe/PS1dE9 (APP/PS1) mice, a well-established mouse model of familial AD. It is well known that molecules like cAMP response element binding (CREB) and binding protein (CBP) play a crucial role in memory consolidation. We analyzed CBP on its transcriptional activity and protein levels, finding a significant downregulation of both of them at 3-month-old mice...
July 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28751935/chk1-promotes-dna-damage-response-bypass-following-oxidative-stress-in-a-model-of-hydrogen-peroxide-associated-ulcerative-colitis-through-jnk-inactivation-and-chromatin-binding
#15
Kathrin Reissig, Andrew Silver, Roland Hartig, Antje Schinlauer, Diana Walluscheck, Thomas Guenther, Sandra Siedentopf, Jochen Ross, Diep-Khanh Vo, Albert Roessner, Angela Poehlmann-Nitsche
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28750653/bacteraemic-urinary-tract-infections-in-a-tertiary-hospital-in-japan-the-epidemiology-of-community-acquired-infections-and-the-role-of-non-carbapenem-therapy
#16
Momoko Mawatari, Kayoko Hayakawa, Yoshihiro Fujiya, Kei Yamamoto, Satoshi Kutsuna, Nozomi Takeshita, Norio Ohmagari
OBJECTIVES: This study aimed to describe the epidemiology of bacteraemic urinary tract infections (UTIs), especially those that were community-acquired (i.e., with no discernible healthcare-associated exposure) and caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLPE). We also evaluated and compared empirical antimicrobial treatments [carbapenem (CBP) vs. non-carbapenem beta-lactam (non-CBPBL)] for bacteraemic UTIs. Finally, we reviewed the published literature on the effectiveness of non-CBP compared to CBP treatments for UTIs caused by extended-spectrum beta-lactamase-producing organisms...
July 27, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28750409/timp-2-igfbp7-nephrocheck%C3%A2-measurements-at-intensive-care-unit-admission-after-cardiac-surgery-are-predictive-for-acute-kidney-injury-within-48-hours
#17
Mehmet Oezkur, Attila Magyar, Phillip Thomas, Tabea Stork, Reinhard Schneider, Constanze Bening, Stefan Störk, Peter U Heuschmann, Rainer G Leyh, Martin Wagner
BACKGROUND/AIMS: Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass...
July 27, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28748608/four-years-comparative-follow-up-evaluation-of-community-based-step-down-and-residential-specialist-psychodynamic-programmes-for-personality-disorders
#18
Marco Chiesa, Antonella Cirasola, Peter Fonagy
Although the fulcrum of service provision for personality disorder (PD) has shifted from hospital-based to psychodynamically- and cognitively-oriented outpatient programmes, very few studies have attempted to compare specialist moderate intensity outpatient programmes with specialist high-intensity residential models, or to explore whether a period of inpatient treatment may be necessary to improve outcome and prognosis. In this article, we prospectively compare changes over a 4-year period in 3 groups of patients with personality disorders (N = 162) treated in a specialist community-based (CBP, N = 30), a step-down (RT-CBP, N = 87), and a specialist residential programme (RT, N = 45) in psychiatric distress, deliberate self-injury, and suicide attempt using multilevel modelling and multivariate logistic regression analyses...
July 26, 2017: Clinical Psychology & Psychotherapy
https://www.readbyqxmd.com/read/28743336/-analysis-of-factors-affecting-the-prognosis-of-icu-patients-by-multiple-logistic-regression-model-a-retrospective-cohort-study-of-1-299-patients-in-12-consecutive-years
#19
Jianfeng Liang, Zhiyong Li, Yan Zhang, Wei Zhang, Haishan Dong, Yun Zhang, Chang Xu, Maolong Gao
OBJECTIVE: To explore the prognostic factors of intensive care unit (ICU) patients. METHODS: A retrospective cohort study was conducted. The clinical data of patients admitted to ICU of Beijing Geriatric Hospital from January 2005 to December 2016 were collected. According to the prognosis, the patients were divided into death group and survival group, and the mortality trend with time and age was observed. Survival and death were treated as dependent variables, while the gender, age, reason of ICU admission, acute physiology and chronic health evaluation II (APACHE II) score, whether undergoing invasive mechanical ventilation (MV), invasive MV reason, duration of invasive MV, whether successful weaning, whether ICU nosocomial infection, hospital acquired pneumonia (HAP), central line-associated bloodstream infection (CLABSI), acute kidney injury (AKI) occurred, whether undergoing continuous blood purification (CBP), whether septic shock occurred, whether undergoing invasive hemodynamic monitoring or blood transfusion and length of ICU stay were used as the independent variables...
July 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28740501/hac1-and-haf1-histone-acetyltransferases-have-different-roles-in-uv-b-responses-in-arabidopsis
#20
Julieta P Fina, Fiorella Masotti, Sebastián P Rius, Franco Crevacuore, Paula Casati
Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling...
2017: Frontiers in Plant Science
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