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https://www.readbyqxmd.com/read/28806782/the-use-of-18f-fluoro-deoxy-glucose-positron-emission-tomography-18f-fdg-pet-as-a-non-invasive-pharmacodynamic-biomarker-to-determine-the-minimally-pharmacologically-active-dose-of-azd8835-a-novel-pi3k%C3%AE-inhibitor
#1
Juliana Maynard, Sally-Ann Emmas, Francois-Xavier Ble, Herve Barjat, Emily Lawrie, Urs Hancox, Urszula M Polanska, Alison Pritchard, Kevin Hudson
BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development...
2017: PloS One
https://www.readbyqxmd.com/read/28806404/rig-i-and-il-6-are-negative-feedback-regulators-of-sting-induced-by-double-stranded-dna
#2
Xueling Wu, Jun Yang, Tao Na, Kehua Zhang, Andrew M Davidoff, Bao-Zhu Yuan, Youchun Wang
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA)...
2017: PloS One
https://www.readbyqxmd.com/read/28805715/identification-and-analysis-of-mitogen-activated-protein-kinase-mapk-cascades-in-fragaria-vesca
#3
Heying Zhou, Suyue Ren, Yuanfang Han, Qing Zhang, Ling Qin, Yu Xing
Mitogen-activated protein kinase (MAPK) cascades are highly conserved signaling modules in eukaryotes, including yeasts, plants and animals. MAPK cascades are responsible for protein phosphorylation during signal transduction events, and typically consist of three protein kinases: MAPK, MAPK kinase, and MAPK kinase kinase. In this current study, we identified a total of 12 FvMAPK, 7 FvMAPKK, 73 FvMAPKKK, and one FvMAPKKKK genes in the recently published Fragaria vesca genome sequence. This work reported the classification, annotation and phylogenetic evaluation of these genes and an assessment of conserved motifs and the expression profiling of members of the gene family were also analyzed here...
August 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28805491/intermedin-inhibits-unilateral-ureteral-obstruction-induced-oxidative-stress-via-nadph-oxidase-nox4-and-camp-dependent-mechanisms
#4
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yue Qi, Yun Fan, Zhiqiang Peng
NADPH oxidase Nox4-derived reactive oxygen species (ROS) play important roles in renal fibrosis. Our previous study demonstrated that intermedin (IMD) alleviated unilateral ureteral obstruction (UUO)-induced renal fibrosis by inhibition of ROS. However, the precise mechanisms remain unclear. Herein, we investigated the effect of IMD on Nox4 expression and NADPH oxidase activity in rat UUO model, and explored if these effect were achieved through cAMP-PKA pathway, the important post-receptor signal transduction pathway of IMD, in TGF-β1-stimulated rat proximal tubular cell (NRK-52E)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28805145/pdgf-vegf-related-receptor-affects-transglutaminase-activity-to-control-cell-migration-during-crustacean-hematopoiesis
#5
Kingkamon Junkunlo, Chadanat Noonin, Kenneth Söderhäll, Irene Söderhäll
The platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor whose ligand is PDGF, is crucial in the transduction of extracellular signals into cells and mediates numerous processes, such as cell proliferation, differentiation, survival and migration. We demonstrate the important roles of a receptor tyrosine kinase related to the PDGF/VEGF family protein (PVR) in controlling hematopoietic progenitor cell migration by affecting extracellular transglutaminase (TGase) activity. Pl_PVR1, GenBank accession number KY444650, is highly expressed in hemocytes and the hematopoietic tissue (HPT)...
August 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28804499/empirical-comparison-of-visualization-tools-for-larger-scale-network-analysis
#6
REVIEW
Georgios A Pavlopoulos, David Paez-Espino, Nikos C Kyrpides, Ioannis Iliopoulos
Gene expression, signal transduction, protein/chemical interactions, biomedical literature cooccurrences, and other concepts are often captured in biological network representations where nodes represent a certain bioentity and edges the connections between them. While many tools to manipulate, visualize, and interactively explore such networks already exist, only few of them can scale up and follow today's indisputable information growth. In this review, we shortly list a catalog of available network visualization tools and, from a user-experience point of view, we identify four candidate tools suitable for larger-scale network analysis, visualization, and exploration...
2017: Advances in Bioinformatics
https://www.readbyqxmd.com/read/28804449/loss-of-leptin-induced-modulation-of-hippocampal-synaptic-trasmission-and-signal-transduction-in-high-fat-diet-fed-mice
#7
Marco Mainardi, Matteo Spinelli, Federico Scala, Andrea Mattera, Salvatore Fusco, Marcello D'Ascenzo, Claudio Grassi
Hippocampal plasticity is triggered by a variety of stimuli including sensory inputs, neurotrophins and inflammation. Leptin, whose primary function is to regulate food intake and energy expenditure, has been recently shown to affect hippocampal neurogenesis and plasticity. Interestingly, mice fed a high-fat diet (HFD) exhibit impaired hippocampal function, but the underlying mechanisms are poorly understood. To address this issue, we compared leptin responsiveness of hippocampal neurons in control and HFD-fed mice by combining single-cell electrophysiology and biochemical assays...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28803370/ip3-receptor-signaling-and-endothelial-barrier-function
#8
REVIEW
Mitchell Y Sun, Melissa Geyer, Yulia A Komarova
The endothelium, a monolayer of endothelial cells lining vessel walls, maintains tissue-fluid homeostasis by restricting the passage of the plasma proteins and blood cells into the interstitium. The ion Ca(2+), a ubiquitous secondary messenger, initiates signal transduction events in endothelial cells that is critical to control of vascular tone and endothelial permeability. The ion Ca(2+) is stored inside the intracellular organelles and released into the cytosol in response to environmental cues. The inositol 1,4,5-trisphosphate (IP3) messenger facilitates Ca(2+) release through IP3 receptors which are Ca(2+)-selective intracellular channels located within the membrane of the endoplasmic reticulum...
August 12, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28802691/the-genome-analysis-of-oleiphilus-messinensis-me102-dsm-13489-t-reveals-backgrounds-of-its-obligate-alkane-devouring-marine-lifestyle
#9
Stepan V Toshchakov, Alexei A Korzhenkov, Tatyana N Chernikova, Manuel Ferrer, Olga V Golyshina, Michail M Yakimov, Peter N Golyshin
Marine bacterium Oleiphilus messinensis ME102 (DSM 13489(T)) isolated from the sediments of the harbor of Messina (Italy) is a member of the order Oceanospirillales, class Gammaproteobacteria, representing the physiological group of marine obligate hydrocarbonoclastic bacteria (OHCB) alongside the members of the genera Alcanivorax, Oleispira, Thalassolituus, Cycloclasticus and Neptunomonas. These organisms play a crucial role in the natural environmental cleanup in marine systems. Despite having the largest genome (6...
August 9, 2017: Marine Genomics
https://www.readbyqxmd.com/read/28802582/label-free-quantitative-proteomic-analysis-of-lactobacillus-fermentum-ncdc-400-during-bile-salt-exposure
#10
Gurjeet Kaur, Syed Azmal Ali, Sudarshan Kumar, Ashok Kumar Mohanty, Pradip Behare
Lactobacillus fermentum NCDC 400 is a commonly used and a comprehensively studied probiotic organism. The distinctive capability to endure the harsh environment of the gastrointestinal tract owing to the presence of bile salts in gastric juice facilitates gut microbiota, especially the probiotic organisms to transiently inhabit the host gut. In the present study, Label-Free Quantification (LFQ) approach has been employed to analyze the expression pattern of Lactobacillus fermentum NCDC 400 strain proteins, under bile acid stress, using high-resolution mass spectrometer connected to nano-liquid chromatography (LC) system...
August 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28802267/development-of-a-transient-muts-based-hypermutation-system-for-adaptive-evolution-of-lactobacillus-casei-to-low-ph
#11
Tom J Overbeck, Dennis L Welker, Joanne E Hughes, James L Steele, Jeff R Broadbent
This study explored transient inactivation of the gene encoding the DNA mismatch repair enzyme MutS as a tool for adaptive evolution of Lactobacillus casei MutS deletion derivatives of L. casei 12A and ATCC 334 were constructed and subject to a 100-day adaptive evolution process to increase lactic acid resistance at low pH. Wild-type parental strains were also subject to this treatment. At the end of the process, the ΔmutS lesion was repaired in representative L. casei 12A and ATCC 334 ΔmutS isolates. Growth studies in broth at pH 4...
August 11, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28801966/ursolic-acid-a-natural-nutraceutical-agent-targets-caspase3-and-alleviates-inflammation-associated-downstream-signal-transduction
#12
Xiaoyao Ma, Yuan Zhang, Zengyong Wang, Yunbing Shen, Man Zhang, Quandeng Nie, Yuanyuan Hou, Gang Bai
SCOPE: Ursolic acid (UA) is a pentacyclicterpenoid carboxylic acid that is present in a wide variety of plant foods. There are many beneficial health effects that are attributed to the properties of UA. However, the specific cellular targets of UA and the mechanism underlying downstream signal transduction processes linked to the anti-inflammation pathway have not been thoroughly elucidated to date. METHODS AND RESULTS: Chemical biology strategies such as target fishing, click reaction synthesis of a UA probe and molecular imaging were used to identify potential target proteins of UA...
August 11, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28801239/salsalate-activates-skeletal-muscle-thermogenesis-and-protects-mice-from-high-fat-diet-induced-metabolic-dysfunction
#13
Li Nie, Xin-Lu Yuan, Ke-Tao Jiang, Yu-Hui Jiang, Jin Yuan, Lan Luo, Shi-Wei Cui, Cheng Sun
Salsalate plays beneficial roles for ameliorating hyperglycemia and dyslipidemia in type 2 diabetes patients, but the underlying mechanisms are still poorly understood. In this study, by administering salsalate to mice fed with high fat diet and examining how salsalate rectifies metabolic dysfunction in these obese mice, we found that salsalate stimulated body temperature and attenuated body weight gain without affecting food intake. Our results showed that salsalate application decreased lipid accumulation in liver and epididymal white adipose tissue (eWAT), inhibited hepatic gluconeogenesis and improved insulin signaling transduction in eWAT...
August 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28800782/effects-of-chinese-medicinal-herbs-on-expression-of-brain-derived-neurotrophic-factor-bdnf-and-its-interaction-with-human-breast-cancer-mda-mb-231-cells-and-endothelial-huvecs
#14
Jen-Hwey Chiu, Fang-Pey Chen, Yi-Fang Tsai, Man-Ting Lin, Ling-Ming Tseng, Yi-Ming Shyr
BACKGROUND: Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF. METHODS: Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on cancer cells alone, on endothelial cells alone and on cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays...
August 12, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28800633/feeding-fasting-dependent-recruitment-of-membrane-microdomain-proteins-to-lipid-droplets-purified-from-the-liver
#15
Kritika Sadh, Priyanka Rai, Roop Mallik
Lipid droplets (LDs) are cellular stores of neutral fat that facilitate lipid and protein trafficking in response to metabolic cues. Unlike other vesicles, the phospholipid membrane on the LD is a monolayer. Interestingly, this monolayer membrane has free cholesterol, and may therefore contain lipid microdomains that serve as a platform for assembling proteins involved in signal transduction, cell polarity, pathogen entry etc. In support of this, cell culture studies have detected microdomain-associated "raftophilic" proteins on LDs...
2017: PloS One
https://www.readbyqxmd.com/read/28799168/small-scaffolds-big-potential-developing-miniature-proteins-as-therapeutic-agents
#16
Justin M Holub
Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs...
August 10, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28799069/rae1-mediated-nuclear-export-of-rnc1-is-an-important-determinant-in-controlling-mapk-signaling
#17
REVIEW
Ryosuke Satoh, Kanako Hagihara, Reiko Sugiura
In eukaryotic cells, RNA binding proteins (RBPs) play critical roles in regulating almost every aspect of gene expression, often shuttling between the nucleus and the cytoplasm. They are also key determinants in cell fate via controlling the target mRNAs under the regulation of various signaling pathways in response to environmental stresses. Therefore, understanding the mechanisms that couple the location of mRNA and RBPs is a major challenge in the field of gene expression and signal responses. In fission yeast, a KH-type RBP Rnc1 negatively regulates MAPK signaling activation via mRNA stabilization of the dual-specificity MAPK phosphatase Pmp1, which dephosphorylates MAPK Pmk1...
August 10, 2017: Current Genetics
https://www.readbyqxmd.com/read/28798468/the-bitter-taste-receptor-tas2r16-achieves-high-specificity-and-accommodates-diverse-glycoside-ligands-by-using-a-two-faced-binding-pocket
#18
Anu Thomas, Chidananda Sulli, Edgar Davidson, Eli Berdougo, Morganne Phillips, Bridget A Puffer, Cheryl Paes, Benjamin J Doranz, Joseph B Rucker
Although bitter taste receptors (TAS2Rs) are important for human health, little is known of the determinants of ligand specificity. TAS2Rs such as TAS2R16 help define gustatory perception and dietary preferences that ultimately influence human health and disease. Each TAS2R must accommodate a broad diversity of chemical structures while simultaneously achieving high specificity so that diverse bitter toxins can be detected without all foods tasting bitter. However, how these G protein-coupled receptors achieve this balance is poorly understood...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798160/protein-coalation-a-redox-linked-post-translational-modification
#19
Steven C Ley, Luiz Pedro S de Carvalho
Regulation of metabolic pathways by signal transduction and transcriptional cascades can alter cellular levels of metabolites. Metabolites themselves can also have regulatory activity as shown in a new study published in the Biochemical Journal Tsuchiya et al. describe a novel antibody and mass spectrometry-based method for identifying proteins that are reversibly modified with Coenzyme A (CoA). Analysis of the 'CoAlated proteome' under conditions of oxidative and metabolic stress revealed a bias towards the modification of metabolic enzymes by CoA...
August 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28798148/ubiquitination-of-basal-vegfr2-regulates-signal-transduction-and-endothelial-function
#20
Gina A Smith, Gareth W Fearnley, Izma Abdul-Zani, Stephen B Wheatcroft, Darren C Tomlinson, Michael A Harrison, Sreenivasan Ponnambalam
Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulates signal transduction and angiogenesis but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated response by endothelial cells...
August 10, 2017: Biology Open
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