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Activator protein 1

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https://www.readbyqxmd.com/read/28549343/hmgb1-mediated-autophagy-attenuates-gemcitabine-induced-apoptosis-in-bladder-cancer-cells-involving-jnk-and-erk-activation
#1
Hubin Yin, Xiaoyu Yang, Wen Gu, Yan Liu, Xinyuan Li, Xiaolong Huang, Xin Zhu, Yong Tao, Xin Gou, Weiyang He
High-mobility group box 1 (HMGB1) has been found to mediate autophagy during chemotherapy in several cancers. However, whether HMGB1plays a role in autophagy and chemoresistance in bladder cancer is elusive. In this report, HMGB1 expression was found to be increased in 30 primary bladder cancer tissue specimens compared to their matched adjacent non-tumor tissues. While gemcitabine induced apoptotic cell death, it also induced HMGB1 expression and autophagy in bladder cancer T24 and BIU-87 cells. Suppressing HMGB1 expression with siRNA strongly potentiated gemcitabine-induced apoptosis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549327/achievement-performance-and-characteristics-of-microbial-products-in-a-partial-nitrification-sequencing-batch-reactor-as-a-pretreatment-for-anaerobic-ammonium-oxidation
#2
Heng Dong, Keyi Zhang, Xiao Han, Bin Du, Qin Wei, Dong Wei
This study was carried out to evaluate achievement, performance and characteristics of microbial products in a partial nitrification sequencing batch reactor as a pretreatment for anaerobic ammonium oxidation (anammox). After 100 days long-term operation, the effluent NO2(-)-N/NH4(+)N ratio of the reactor was average at 1.3 and NO3(-)-N concentration was low by controlling low dissolved oxygen (DO) concentration, which was considered as the ideal influent for anammox. Specific oxygen uptake rate (SOUR) implied that (SOUR)NH4 and (SOUR)NO2 of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) in sludge changed from 21...
May 20, 2017: Chemosphere
https://www.readbyqxmd.com/read/28549219/design-synthesis-and-properties-of-a-potent-inhibitor-of-pseudomonas-aeruginosa-deacetylase-lpxc
#3
Grazia Piizzi, David T Parker, Yunshan Peng, Markus Rolf Dobler, Anup Patnaik, Som Wattanasin, Eugene Liu, Francois Lenoir, Jill Nunez, John Kerrigan, David McKenney, Colin S Osborne, Donghui Yu, Leanne Lanieri, Jade Bojkovic, JoAnne Dzink-Fox, Maria-Dawn Lilly, Elizabeth R Sprague, Yipin Lu, Hongming Wang, Srijan Ranjitkar, Bing Wang, Meir Glick, Lawrence G Hamann, Ruben Tommasi, Xia Yang, Charles R Dean
Over the past several decades the frequency of antibacterial resistance in hospitals, including multi-drug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28549218/exosite-2-directed-ligands-attenuate-protein-c-activation-by-the-thrombin-thrombomodulin-complex
#4
Kai Chen, Alan R Stafford, Chengliang Wu, Calvin Yeh, Paul Y Kim, James C Fredenburgh, Jeffrey I Weitz
Thrombin activity, inhibition, and localization are regulated by two exosites that flank the active site. Substrates, cofactors and inhibitors bind to exosite 1 to promote active site access, whereas exosite 2 interactions retain thrombin on cells, platelets, and proteins. The exosites also serve allosteric roles, whereby ligand binding alters thrombin activity. Previously, we showed that ligands that bind exosite 2 attenuate the exosite 1-mediated interaction of thrombin with fibrin, demonstrating allosteric connection between the exosites...
May 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28549169/regulatory-dynamics-of-11p13-suggest-a-role-for-ehf-in-modifying-cf-lung-disease-severity
#5
Lindsay R Stolzenburg, Rui Yang, Jenny L Kerschner, Sara Fossum, Matthew Xu, Andrew Hoffmann, Kay-Marie Lamar, Sujana Ghosh, Sarah Wachtel, Shih-Hsing Leir, Ann Harris
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good predictors of lung phenotype. Genome-wide association studies (GWAS) previously identified additional genomic sites associated with CF lung disease severity. One of these, at chromosome 11p13, is an intergenic region between Ets homologous factor (EHF) and Apaf-1 interacting protein (APIP). Our goal was to determine the functional significance of this region, which being intergenic is probably regulatory...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28549152/mdsnrk1-1-interacts-with-mdjaz18-to-regulate-sucrose-induced-anthocyanin-and-proanthocyanidin-accumulation-in-apple
#6
Xiao-Juan Liu, Xiu-Hong An, Xin Liu, Da-Gang Hu, Xiao-Fei Wang, Chun-Xiang You, Yu-Jin Hao
Sugars induce anthocyanin biosynthesis in plants. As a conserved energy sensor, SnRK1 (SNF1-related kinase 1) is involved in sucrose-induced anthocyanin accumulation. However, the exact molecular mechanism by which SnRK1 regulates the biosynthesis of anthocyanins and proanthocyanidins (PAs) in response to sucrose in plants is not clear. In this study, it was found that MdSnRK1.1 interacted with MdJAZ18 protein which acts as a repressor in the jasmonate (JA) signaling pathway. MdSnRK1.1 then phosphorylated MdJAZ18 to facilitate its 26S proteasome-mediated degradation, which released MdbHLH3 thereby activating the expression of the regulatory and structural genes, thus finally promoting the biosynthesis of anthocyanins and PAs...
May 25, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28549098/high-protein-foods-and-physical-activity-protect-against-age-related-muscle-loss-and-functional-decline
#7
M Loring Bradlee, Jabed Mustafa, Martha R Singer, Lynn L Moore
Background: Some clinical trials suggest that protein supplementation enhances the effects of resistance exercise on skeletal muscle mass (SMM); fewer studies examine the effects of diets rich in protein-source foods on SMM and functional status among community-dwelling adults. Methods: Data from the Framingham Offspring study including diet (three-day records, exams 3 and 5), physical activity (exams 2 and 4), percent SMM (%SMM) (exams 6 and 7), and functional performance (exams 5 through 8) were used to evaluate independent and combined effects of physical activity and high-protein foods on adjusted mean %SMM (using analysis of covariance) and risk of functional decline (using Cox proportional hazard's models)...
May 25, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28549058/histone-deacetylase-adaptation-in-single-ventricle-heart-disease-and-a-young-animal-model-of-right-ventricular-hypertrophy
#8
Weston W Blakeslee, Kimberly M Demos-Davies, Douglas D Lemon, Katharina M Lutter, Maria A Cavasin, Sam Payne, Karin Nunley, Carlin S Long, Timothy A McKinsey, Shelley D Miyamoto
BACKGROUNDHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac disease. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle heart disease of right ventricular morphology (SV), as well as in a rodent model of right ventricular hypertrophy (RVH).METHODSHomogenates of RV explants from non-failing controls and SV children were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day old rat pups were placed in hypoxic conditions and echocardiographic analysis, gene expression, HDAC catalytic activity and isoform expression studies of the RV were performed...
May 26, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28548975/factor-vii-activating-protease-sex-related-association-with-coronary-artery-calcification
#9
Ramshanker Ramanathan, Jørgen B Gram, Niels Peter R Sand, Bjarne L Nørgaard, Axel C P Diederichsen, Frank Vitzthum, Herbert Schwarz, Johannes J Sidelmann
: Factor VII-activating protease (FSAP) may regulate development of cardiovascular disease (CVD). We evaluated sex differences in FSAP measures and examined the association between FSAP and coronary artery calcification (CAC) in a middle-aged population. Participants were randomly selected citizens aged 50 or 60 without CVD, diabetes mellitus, Marburg I polymorphism, or hormone replacement therapy (HRT). FSAP protein concentration (total FSAP), FSAP urokinase-activating capacity (FSAP GP), and FSAP GP/total FSAP (specific FSAP activity) were measured...
May 25, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28548960/severe-hypertriglyceridemia-due-to-two-novel-loss-of-function-lipoprotein-lipase-gene-mutations-c310r-e396v-in-a-chinese-family-associated-with-recurrent-acute-pancreatitis
#10
Yu Lun, Xiaofang Sun, Ping Wang, Jingwei Chi, Xu Hou, Yangang Wang
Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548959/identification-of-the-histone-lysine-demethylase-kdm4a-jmjd2a-as-a-novel-epigenetic-target-in-m1-macrophage-polarization-induced-by-oxidized-ldl
#11
Xue Wang, Siqing Wang, Gang Yao, Dehai Yu, Kexin Chen, Qian Tong, Long Ye, Chuan Wu, Yue Sun, Haixia Li, Dirk M Hermann, Thorsten R Döppner, Fengyan Jin, Yun Dai, Jiang Wu
Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548950/enolase-1-stimulates-glycolysis-to-promote-chemoresistance-in-gastric-cancer
#12
Xiaoling Qian, Wenxia Xu, Jinye Xu, Qiqi Shi, Jiaqiu Li, Yu Weng, Zhinong Jiang, Lifeng Feng, Xian Wang, Jianwei Zhou, Hongchuan Jin
Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548942/the-n-terminal-tail-coordinates-with-carbohydrate-recognition-domain-to-mediate-galectin-3-induced-apoptosis-in-t-cells
#13
Huiting Xue, Lu Liu, Zihan Zhao, Zhongyu Zhang, Yuan Guan, Hairong Cheng, Yifa Zhou, Guihua Tai
Galectin-3 is a galectin with a unique flexible N-terminal tail (NT) connected to the conserved carbohydrate recognition domain (CRD). Galectin-3 is associated with tumor immune tolerance and exhibits an ability to induce T cell apoptosis. We used Jurkat, Jurkat E6-1 and CEM T-cell lines and human peripheral blood mononuclear cells (PBMCs) to investigate the specific roles of the CRD and NT in inducing T cell apoptosis. Galectin-3 triggered sustained extracellular signal-regulated kinase (ERK) phosphorylation that induced apoptosis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548933/kir2dl5-mutation-and-loss-underlies-sporadic-dermal-neurofibroma-pathogenesis-and-growth
#14
Corina Anastasaki, Sonika Dahiya, David H Gutmann
Dermal neurofibromas (DNFs) are benign peripheral nerve sheath tumors thought to originate from Schwann cell progenitors. These tumors represent one of the hallmarks of the neurofibromatosis type 1 (NF1) tumor predisposition syndrome, where they can number in the thousands. While NF1-DNFs arise due to mutations in the NF1 gene, the vast majority of DNFs occur sporadically (sp-DNFs), where the genetic etiology is currently unknown. Herein, we employed whole-exome sequencing of sp-DNFs to identify a recurrent mutation in the KIR2DL5 gene, which codes for a protein suppressor of natural killer (NK) cell activity...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#15
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548844/two-dynamical-regimes-of-the-substrate-radical-rearrangement-reaction-in-b12-dependent-ethanolamine-ammonia-lyase-resolve-contributions-of-native-protein-configurations-and-collective-configurational-fluctuations-to-catalysis
#16
Meghan Kohne, Chen Zhu, Kurt Warncke
The kinetics of the substrate radical rearrangement reaction step in B12-dependent ethanolamine ammonia-lyase (EAL) from Salmonella typhimurium are measured over a 92 K temperature range. The observed first-order rate constants display a piecewise-continuous Arrhenius dependence, with linear regions over 295→220 K (monoexponential) and 214→203 K (biexponential) that are delineated by a kinetic bifurcation and kinks at 219 and 217 K, respectively. The results are interpreted by using a free energy landscape model and derived microscopic kinetic mechanism...
May 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28548843/zwitterionic-nanocarrier-surface-chemistry-improves-sirna-tumor-delivery-and-silencing-activity-relative-to-polyethylene-glycol
#17
Meredith A Jackson, Thomas A Werfel, Elizabeth J Curvino, Fang Yu, Taylor Elizabeth Kavanaugh, Samantha M Sarett, Mary D Dockery, Kameron V Kilchrist, Ayisha N Jackson, Todd D Giorgio, Craig L Duvall
Although siRNA-based nanomedicines hold promise for cancer treatment, conventional siRNA-polymer complex (polyplex) nanocarrier systems have poor pharmacokinetics following intravenous delivery, hindering tumor accumulation. Here, we determined the impact of surface chemistry on the in vivo pharmacokinetics and tumor delivery of siRNA polyplexes. A library of diblock polymers was synthesized, all containing the same pH-responsive, endosomolytic polyplex core-forming block but different corona blocks: 5 kDa (benchmark) and 20 kDa linear PEG, 10 kDa and 20 kDa brush-like poly(oligo ethylene glycol) (POEGMA), and 10 kDa and 20 kDa zwitterionic phosphorylcholine-based polymers (PMPC)...
May 26, 2017: ACS Nano
https://www.readbyqxmd.com/read/28548702/p16-loss-and-e2f-cell-cycle-deregulation-in-infant-posterior-fossa-ependymoma
#18
Seth C Lummus, Andrew M Donson, Katherine Gowan, Kenneth L Jones, Rajeev Vibhakar, Nicholas K Foreman, B K Kleinschmidt-DeMasters
BACKGROUND: Posterior fossa (PF) ependymomas (EPNs) in infants less than 1 year of age (iEPN-PF) have a poorer clinical outcome than EPNs in older children. While radiation therapy is the standard of care for the latter, it is withheld in infants to avoid neurotoxicity to immature brain. It is unknown whether the adverse outcome in iEPN-PFs is due to treatment differences or aggressive biology. We examined this question using molecular profiling. METHODS: Six anaplastic iEPN-PFs were subjected to transcriptomic analysis and FISH for p16 loss and gains of 1q, and compared with anaplastic PF EPNs from older children...
May 26, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28548684/origins-of-anterior-posterior-polarity-by-localized-activation-of-disheveled
#19
Jeff Chieh-Fu Peng, Lingyu Wang, Athula H Wikramanayake
Most animal eggs have a primordial polarity, termed the animal-vegetal (AV) axis, that frequently predicts the anterior-posterior (AP) axis of the embryo and adult. Transformation of the AV polarity of the egg to the AP polarity of the embryo in many species is mediated by the localized activation of canonical Wnt (cWnt) signaling in vegetal blastomeres by maternal determinants. In the sea urchin egg, cWnt signal transduction is facilitated by localized "activation" of the Disheveled protein, a central regulator of Wnt signaling...
May 26, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28548645/waldenstrom-macroglobulinemia-cells-devoid-of-btk-c481s-or-cxcr4-whim-like-mutations-acquire-resistance-to-ibrutinib-through-upregulation-of-bcl-2-and-akt-resulting-in-vulnerability-towards-venetoclax-or-mk2206-treatment
#20
A Paulus, S Akhtar, H Yousaf, A Manna, S M Paulus, Y Bashir, T R Caulfield, M Kuranz-Blake, K Chitta, X Wang, Y Asmann, R Hudec, W Springer, S Ailawadhi, A Chanan-Khan
Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTK(C481S) and CXCR4(WHIM-like) mutations...
May 26, 2017: Blood Cancer Journal
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