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https://www.readbyqxmd.com/read/28819643/membrane-localization-of-acetylated-cnk1-mediates-a-positive-feedback-on-raf-erk-signaling
#1
Adrian Fischer, Wignand W D Mühlhäuser, Bettina Warscheid, Gerald Radziwill
Spatiotemporal control is a common mechanism that modulates activity and function of signal transducers in the signaling network. We identified acetylation of CNK1 (connector enhancer of kinase suppressor of Ras-1) as a late step in the activation of CNK1 signaling, accompanied with prolonged stimulation of extracellular signal-regulated kinase (ERK). We identified the acetyltransferase CREB (cyclic adenosine 3',5'-monophosphate response element-binding protein)-binding protein and the deacetylase SIRT2 (sirtuin type 2) as novel binding partners of CNK1, modulating the acetylation state of CNK1...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28818385/molecular-cloning-and-characterization-of-ptrzpt2-1-a-zpt2-family-gene-encoding-a-cys2-his2-type-zinc-finger-protein-from-trifoliate-orange-poncirus-trifoliata-l-raf-that-enhances-plant-tolerance-to-multiple-abiotic-stresses
#2
Dechun Liu, Li Yang, Man Luo, Qi Wu, Shanbei Liu, Yong Liu
In plants, most Cys2/His2 (C2H2) zinc finger proteins with two zinc finger domains (ZPT2) are involved in abiotic stress responses. In this study, a ZPT2 family gene PtrZPT2-1 was cloned from trifoliate orange (Poncirus trifoliata (L.) Raf.). PtrZPT2-1 is composed of 245 amino acids, has a putative molecular weight of 25.99kDa and an isoelectric point of 8.41. PtrZPT2-1 contained two C2H2 zinc finger domains, one nuclear localization signal (B-box), one transcription repression domain (DLN-box), and one protein-protein interaction domain (L-box)...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28815465/non-injection-drug-use-and-injection-initiation-assistance-among-people-who-inject-drugs-in-tijuana-mexico
#3
Amen Ben Hamida, Claudia Rafful, Sonia Jain, Shelly Sun, Patricia Gonzalez-Zuniga, Gudelia Rangel, Steffanie A Strathdee, Dan Werb
Although most people who inject drugs (PWID) report receiving assistance during injection initiation events, little research has focused on risk factors among PWID for providing injection initiation assistance. We therefore sought to determine the influence of non-injection drug use among PWID on their risk to initiate others. We used generalized estimating equation (GEE) models on longitudinal data among a prospective cohort of PWID in Tijuana, Mexico (Proyecto El Cuete IV), while controlling for potential confounders...
August 16, 2017: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/28815387/image-guided-surgical-robotic-system-for-percutaneous-reduction-of-joint-fractures
#4
Giulio Dagnino, Ioannis Georgilas, Samir Morad, Peter Gibbons, Payam Tarassoli, Roger Atkins, Sanja Dogramadzi
Complex joint fractures often require an open surgical procedure, which is associated with extensive soft tissue damages and longer hospitalization and rehabilitation time. Percutaneous techniques can potentially mitigate these risks but their application to joint fractures is limited by the current sub-optimal 2D intra-operative imaging (fluoroscopy) and by the high forces involved in the fragment manipulation (due to the presence of soft tissue, e.g., muscles) which might result in fracture malreduction. Integration of robotic assistance and 3D image guidance can potentially overcome these issues...
August 16, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28815022/modeling-of-ras-complexes-supports-roles-in-cancer-for-less-studied-partners
#5
H Billur Engin, Daniel Carlin, Dexter Pratt, Hannah Carter
BACKGROUND: RAS protein interactions have predominantly been studied in the context of the RAF and PI3kinase oncogenic pathways. Structural modeling and X-ray crystallography have demonstrated that RAS isoforms bind to canonical downstream effector proteins in these pathways using the highly conserved switch I and II regions. Other non-canonical RAS protein interactions have been experimentally identified, however it is not clear whether these proteins also interact with RAS via the switch regions...
2017: BMC Biophysics
https://www.readbyqxmd.com/read/28814072/molecular-dynamics-study-of-polystyrene-b-poly-ethylene-oxide-asymmetric-diblock-copolymer-systems
#6
Maria Dobies, Monika Makrocka-Rydzyk, Jacek Jenczyk, Marcin Jarek, Richard J Spontak, Stefan Jurga
Two polystyrene-b-poly(ethylene oxide) (PS-b-PEO) diblock copolymers differing in molecular mass (49 and 78 kDa), but possessing the same PEO cylindrical morphology, are examined to elucidate their molecular dynamics. Of particular interest here is the molecular motion of the PEO blocks involved in the rigid amorphous fraction (RAF). Analysis of complementary thermal calorimetry and X-ray scattering data confirm the presence of a microphase-separated morphology, as well as semi-crystalline structure, in each copolymer...
August 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#7
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#8
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28806393/craf-gene-fusions-in-pediatric-low-grade-gliomas-define-a-distinct-drug-response-based-on-dimerization-profiles
#9
P Jain, T M Fierst, H J Han, T E Smith, A Vakil, P J Storm, A C Resnick, A J Waanders
Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28803054/decolorization-of-reactive-azo-dyes-using-a-sequential-chemical-and-activated-sludge-treatment
#10
Ken Meerbergen, Sam Crauwels, Kris A Willems, Raf Dewil, Jan Van Impe, Lise Appels, Bart Lievens
Textile wastewater contains high concentrations of organic substances derived from diverse dyes and auxiliary chemicals, some of which are non-biodegradable and/or toxic. Therefore, it is essential that textile wastewater is treated and that these substances are removed before being discharged into the environment. A combination of advanced oxidation processes (AOPs) to obtain partial dye degradation followed by a biological treatment has been suggested as a promising method for cost-effective decolorization of wastewater...
August 9, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28801450/genomic-analysis-of-hairy-cell-leukemia-identifies-novel-recurrent-genetic-alterations
#11
Benjamin H Durham, Bartlomiej Getta, Sascha Dietrich, Justin Taylor, Helen Won, James M Bogenberger, Sasinya Scott, Eunhee Kim, Young Rock Chung, Stephen S Chung, Jennifer Hüllein, Tatjana Walther, Lu Wang, Sydney X Lu, Christopher C Oakes, Raoul Tibes, Torsten Haferlach, Barry S Taylor, Martin S Tallman, Michael F Berger, Jae H Park, Thorsten Zenz, Omar Abdel-Wahab
Classical hairy cell leukemia (cHCL) is characterized by a near 100% frequency of the BRAFV600E mutation while ~30% of variant HCL (vHCL) have MAP2K1 mutations. However, recurrent genetic alterations cooperating with BRAFV600E or MAP2K1 mutations in HCL, as well as those in MAP2K1- wildtype vHCL, are not well defined. We therefore performed deep targeted mutational and copy number analysis of cHCL (n=53) and vHCL (n=8). The most common genetic alteration in cHCL outside of BRAFV600E was heterozygous loss of chromosome 7q, the minimally deleted region of which targeted wildtype BRAF, subdividing cHCL into those hemizygous versus heterozygous for the BRAFV600E mutation...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28797845/the-hsp90-inhibitor-nvp-auy922-attenuates-intrinsic-pi3k-inhibitor-resistance-in-kras-mutant-non-small-cell-lung-cancer
#12
Kang-Seo Park, Hannah Yang, Junyoung Choi, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Hanwool Jeon, Sang-We Kim, Dae Ho Lee
More than 25% of non-small cell lung cancers (NSCLCs) carry mutations in KRAS, one of the most common oncogenic drivers in this disease. KRAS-mutant NSCLC responds poorly to currently available therapies; therefore, novel treatment strategies are needed. Here, we describe a particularly promising targeted therapeutic strategy against KRAS mutation-harboring NSCLC intrinsically resistant to treatment by PI3K inhibition. We found that intrinsic resistance to PI3K inhibition derived from RAF/MEK/ERK and RSK activation, bypassing blockage of the PI3K/AKT/mTOR pathway...
August 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28797602/venlafaxine-exerts-antidepressant-effects-possibly-by-activating-mapk-erk1-2-and-p13k-akt-pathways-in-the-hippocampus
#13
Peng Shen, Qingchuan Hu, Meixue Dong, Shunjie Bai, Zihong Liang, Zhi Chen, Pengfei Li, Zicheng Hu, Xiaogang Zhong, Dan Zhu, Haiyang Wang, Peng Xie
Serotonin noradrenaline reuptake inhibitors are effective antidepressant drugs, which include venlafaxine and duloxetine. Venlafaxine is commonly used in a clinical context, but the molecular biological mechanisms behind its effects have not been fully determined. Here, we explored the potential biological effects of venlafaxine on mouse hippocampus. Mice were randomly divided into two groups and injected daily with 0.9% NaCl solution or venlafaxine. A GC-MS-based metabolomic approach was used to identify possible metabolic differences between these groups, and the key proteins involved in the relevant pathways were validated by western blotting...
August 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28795231/radiation-induced-gliomas-a-report-of-four-cases-and-analysis-of-molecular-biomarkers
#14
Tsunehito Nakao, Yasuo Sasagawa, Sumihito Nobusawa, Yasushi Takabatake, Hemragul Sabit, Masashi Kinoshita, Katsuyoshi Miyashita, Yasuhiko Hayashi, Hideaki Yokoo, Mitsutoshi Nakada
Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs...
August 9, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28781955/erbb2-signaling-epigenetically-suppresses-microrna-205-transcription-via-ras-raf-mek-erk-pathway-in-breast-cancer
#15
Takuya Hasegawa, Ryohei Adachi, Hitoshi Iwakata, Takayoshi Takeno, Koji Sato, Toshiyuki Sakamaki
We previously reported that microRNA-205 (miR-205) is downregulated by overexpression of the receptor tyrosine kinase ErbB2 and that ectopic transfection of miR-205 precursor decreases ErbB2 tumorigenicity in soft agar. In this study, we further analyzed the regulatory mechanisms linking ErbB2 overexpression and miR-205 downregulation. In ErbB2-overexpressing breast epithelial cells, miR-205 expression was significantly increased by treatment with MEK inhibitor U0126 or PD98059, Raf-1 inhibitor ZM-336372, and ERK inhibitor SCH772984, but PI3K inhibitor LY294002 and p38 MAPK inhibitor SB203580 had no effect...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28776576/gnas-mutations-in-primary-mucinous-and-non-mucinous-lung-adenocarcinomas
#16
Lauren L Ritterhouse, Marina Vivero, Mari Mino-Kenudson, Lynette M Sholl, A John Iafrate, Valentina Nardi, Fei Dong
GNAS mutations have been described in mucinous and non-mucinous epithelial neoplasms of the appendix, pancreas, and colon, with hotspot GNAS mutations found in up to two-thirds of pancreatic intraductal papillary mucinous neoplasms. Additionally, many GNAS-mutated tumors have concurrent mutations in the Ras/Raf pathway. The clinicopathologic features of GNAS-mutated lung carcinomas, however, have not yet been characterized. Primary lung carcinomas from Brigham and Women's Hospital (n=1282) or Massachusetts General Hospital (n=1070) were genotyped on a targeted massively parallel sequencing panel of oncogenes and tumor suppressor genes including GNAS...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28774796/synergistic-anti-tumor-effect-of-17aag-with-the-pi3k-mtor-inhibitor-nvp-bez235-on-human-melanoma
#17
R Calero, E Morchon, I Martinez-Argudo, R Serrano
Drug resistance by MAPK signaling recovery or activation of alternative signaling pathways, such as PI3K/AKT/mTOR, is an important factor that limits the long-term efficacy of targeted therapies in melanoma patients. In the present study, we investigated the phospho-proteomic profile of RTKs and its correlation with downstream signaling pathways in human melanoma. We found that tyrosine kinase receptors expression correlated with the expression of pivotal downstream components of the RAS/RAF/MAPK and PI3K/AKT/mTOR pathways in melanoma cell lines and tumors...
August 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28767430/decoding-the-full-picture-of-raf1-function-based-on-its-interacting-proteins
#18
Ying Huang, Xiao-Xi Guo, Bing Han, Xu-Min Zhang, Su An, Xin-Yu Zhang, Yang Yang, Ying Liu, Qian Hao, Tian-Rui Xu
Raf1 is a member of the Raf kinase family and regulates many fundamental cell processes, including proliferation, differentiation, apoptosis, motility, and metabolism. However, the functions of Raf1 have not been completely elucidated. To better understand Raf1 function, we investigated the proteins that interacted with Raf1. We identified 198 Raf1 interacting proteins and our data suggested that Raf1 may regulate cell processes through these interactions. These interaction partners were involved in all ten hallmarks of cancer, suggesting that Raf1 is involved in different aspects of carcinogenesis...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765887/down-regulation-of-long-noncoding-rna-rp11-713b9-1-contributes-to-the-cell-viability-in-non%C3%A2-small-cell-lung-cancer-nsclc
#19
Jun Cai, Xuan Wang, Hu Huang, Meng Wang, Zhihong Zhang, Yan Hu, Shihua Yu, Yonghua Yang, Jiyuan Yang
Early diagnosis is essential to reduce lung cancer-associated morbidity and mortality rates; however the lack of diagnostic biomarkers for lung cancer has made this difficult. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) serve important roles in cancer occurrence and progression. The present study investigated the novel lncRNA RP11‑713B9.1, which is the antisense transcript of tumor suppressor in lung cancer 1 (TSLC1). The expression levels of RP11‑713B9.1 and TSLC1 in non‑small cell lung cancer were determined using reverse‑transcription quantitative polymerase chain reaction, which revealed that the expression of RP11‑713B9...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28764012/antioxidative-mechanisms-in-chlorogenic-acid
#20
Jelena Tošović, Svetlana Marković, Jasmina M Dimitrić Marković, Miloš Mojović, Dejan Milenković
Although chlorogenic acid (5CQA) is an important ingredient of various foods and beverages, mechanisms of its antioxidative action have not been fully clarified. Besides electron spin resonance experiment, this study includes thermodynamic and mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct formation (RAF), sequential proton loss electron transfer (SPLET), and single electron transfer - proton transfer (SET-PT) mechanisms of 5CQA in benzene, ethanol, and water solutions. The calculations were performed using the M06-2X/6-311++G(d,p) level of theory and CPCM solvation model...
December 15, 2017: Food Chemistry
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