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https://www.readbyqxmd.com/read/28813704/p38-kinase-sgk1-and-nf-%C3%AE%C2%BAb-dependent-up-regulation-of-na-ca2-exchanger-expression-and-activity-following-tgf%C3%A3-1-treatment-of-megakaryocytes
#1
Tamer Al-Maghout, Lisann Pelzl, Itishri Sahu, Basma Sukkar, Zohreh Hosseinzadeh, Ravi Gutti, Stefan Laufer, Jakob Voelkl, Burkert Pieske, Meinrad Gawaz, Florian Lang
BACKGROUND: TGFβ1, a decisive regulator of megakaryocyte maturation and platelet formation, has previously been shown to up-regulate both, store operated Ca2+ entry (SOCE) and Ca2+ extrusion by Na+/Ca2+ exchange. The growth factor thus augments the increase of cytosolic Ca2+ activity ([Ca2+]i) following release of Ca2+ from intracellular stores and accelerates the subsequent decline of [Ca2+]i. The effect on SOCE is dependent on a signaling cascade including p38 kinase, serum & glucocorticoid inducible kinase SGK1, and nuclear factor NFκB...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813526/mtor-has-a-developmental-stage-specific-role-in-mitochondrial-fitness-independent-of-conventional-mtorc1-and-mtorc2-and-the-kinase-activity
#2
Khalid W Kalim, Shuangmin Zhang, Xiaoyi Chen, Yuan Li, Jun-Qi Yang, Yi Zheng, Fukun Guo
The mammalian target of rapamycin (mTOR), present in mTOR complex 1 (mTORC1) and mTORC2, is a serine/threonine kinase that integrates nutrients, growth factors, and cellular energy status to control protein synthesis, cell growth, survival and metabolism. However, it remains elusive whether mTOR plays a developmental stage-specific role in tissue development and whether mTOR can function independent of its complexes and kinase activity. In this study, by inducible genetic manipulation approach, we investigated the role of mTOR and its dependence on mTOR complexes and kinase activity in mitochondrial fitness of early, progenitor stage (lineage-negative; Lin-) versus later, lineage-committed stage (lineage-positive; Lin+) of hematopoietic cells...
2017: PloS One
https://www.readbyqxmd.com/read/28813521/correction-liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#3
Clinton M Hasenour, Martha L Wall, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
[This corrects the article DOI: 10.1371/journal.pone.0170382.].
2017: PloS One
https://www.readbyqxmd.com/read/28813514/the-helicobacter-pylori-type-iv-secretion-system-promotes-il-8-synthesis-in-a-model-of-pediatric-airway-epithelium-via-p38-map-kinase
#4
Myra G Dela Pena-Ponce, Monica T Jimenez, Lori M Hansen, Jay V Solnick, Lisa A Miller
Epidemiologic studies have reported an inverse relationship between childhood Helicobacter pylori infection and development of allergic asthma. Because lung epithelium plays an important role in allergic asthma pathogenesis, we hypothesized that H. pylori may directly influence airway epithelial cell innate immune function, particularly in early childhood. To test our hypothesis, we established an in vitro H. pylori infection model using primary tracheobronchial epithelial cell cultures derived from infant, juvenile and adult rhesus monkeys...
2017: PloS One
https://www.readbyqxmd.com/read/28813415/cdk4-6-inhibition-triggers-anti-tumour-immunity
#5
Shom Goel, Molly J DeCristo, April C Watt, Haley BrinJones, Jaclyn Sceneay, Ben B Li, Naveed Khan, Jessalyn M Ubellacker, Shaozhen Xie, Otto Metzger-Filho, Jeremy Hoog, Matthew J Ellis, Cynthia X Ma, Susanne Ramm, Ian E Krop, Eric P Winer, Thomas M Roberts, Hye-Jung Kim, Sandra S McAllister, Jean J Zhao
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813193/local-detection-of-ptdins3p-at-autophagosome-biogenesis-membrane-platforms
#6
Anna Chiara Nascimbeni, Patrice Codogno, Etienne Morel
Phosphatidylinositol 3-phosphate (PtdIns3P) is a key player of membrane trafficking regulation, mostly synthesized by the PIK3C3 lipid kinase. The presence of PtdIns3P on endosomes has been demonstrated; however, the role and dynamics of the pool of PtdIns3P dedicated to macroautophagy/autophagy remains elusive. Here we addressed this question by studying the mobilization of PtdIns3P in time and space during autophagosome biogenesis. We compared different dyes known to specifically detect PtdIns3P by fluorescence microscopy analysis, based on PtdIns3P-binding FYVE and PX domains, and show that these transfected dyes induce defects in endosomal dynamics as well as artificial and sustained autophagosome formation...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28813015/transcriptional-responses-of-creeping-bentgrass-to-2-3-butanediol-a-bacterial-volatile-compound-bvc-analogue
#7
Yi Shi, Kuiju Niu, Bingru Huang, Wenhui Liu, Huiling Ma
Bacterial volatile compounds (BVCs) have been reported to enhance plant growth and elicit plant defenses against fungal infection and insect damage. The objective of this study was to determine transcriptomic changes in response to synthetic BVC that could be associated with plant resistance to Rhizoctonia solani in creeping bentgrass. The 2,3-butanediol (BD) (250 µM) was sprayed on creeping bentgrass leaves grown in jam jars. The result showed that synthetic BD induced plant defense against R. solani for creeping bentgrass...
August 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28812968/jnk-pathway-in-osteoarthritis-pathological-and-therapeutic-aspects
#8
Hong-Xing Ge, Fu-Man Zou, Yan Li, An-Min Liu, Min Tu
CONTEXT: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway. OBJECTIVE: In this study, we have reviewed the recent updates on the association of JNK pathway with OA. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28812918/tyrosine-kinase-inhibitors-for-advanced-or-metastatic-thyroid-cancer-a-meta-analysis-of-randomized-controlled-trials
#9
Jen-Wei Liu, Chiehfeng Chen, El-Wui Loh, Chun-Cheng Chu, Mu-Yi Wang, Hsin-Ju Ouyang, Ya-Ting Chang, Wei-Zhan Zhuang, Ching-Wen Chou, Der-Jr Huang, Chia-Hwa Lee, Yun Yen, Ka-Wai Tam
BACKGROUND AND AIMS: Radioiodine-refractory advanced or metastatic thyroid cancer has poor prognosis. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) for advanced or metastatic thyroid cancer treatment. METHODS: Studies published until April 2017 were selected. The pooled effect size was calculated through meta-analysis by using random effects models. Outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (RR), and adverse events (AEs)...
August 16, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28812634/optimization-of-lag-phase-shapes-the-evolution-of-a-bacterial-enzyme
#10
Bharat V Adkar, Michael Manhart, Sanchari Bhattacharyya, Jian Tian, Michael Musharbash, Eugene I Shakhnovich
Mutations provide the variation that drives evolution, yet their effects on fitness remain poorly understood. Here we explore how mutations in the essential enzyme adenylate kinase (Adk) of Escherichia coli affect multiple phases of population growth. We introduce a biophysical fitness landscape for these phases, showing how they depend on molecular and cellular properties of Adk. We find that Adk catalytic capacity in the cell (the product of activity and abundance) is the major determinant of mutational fitness effects...
April 28, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812460/myopathic-mtdna-depletion-syndrome-due-to-mutation-in-tk2-gene
#11
Elena Martín-Hernández, María Teresa García-Silva, Pilar Quijada-Fraile, María Elena Rodríguez-García, Henry Rivera, Aurelio Hernández-Laín, David Coca-Robinot, Joaquín Fernández-Toral, Joaquín Arenas, Miguel A Martín, Francisco Martínez-Azorín
Whole-exome sequencing was used to identify the disease gene(s) in a Spanish girl with failure to thrive, muscle weakness, mild facial weakness, elevated creatine kinase, deficiency of mitochondrial complex III and depletion of mtDNA. With whole-exome sequencing data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The analysis of whole exome uncovered a homozygous pathogenic mutation in thymidine kinase 2 gene ( TK2; NM_004614.4:c.323 C>T, p.T108M)...
September 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#12
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812431/oral-administration-of-curcumin-attenuates-visceral-hyperalgesia-through-inhibiting-phosphorylation-of-trpv1-in-rat-model-of-ulcerative-colitis
#13
Mei Yang, Juan Wang, Chunxue Yang, Hongxiu Han, Weifang Rong, Guohua Zhang
Background Curcumin has been reported to have anti-inflammatory and anti-nociceptive effects. The present study was designed to explore the potential therapeutic effects of curcumin on visceral hyperalgesia and inflammation in a rat model of ulcerative colitis. We observed the effects of orally administered curcumin on the disease activity index, histological change in colon, colorectal distension-induced abdominal withdrawal reflex, the expression of transient receptor potential vanilloid 1 (TRPV1) and phosphorylated TRPV1 in dextran sulfate sodium-induced colitis rats...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28812308/transcriptional-regulation-of-the-protein-kinase-a-subunits-in-saccharomyces-cerevisiae-during-fermentative-growth
#14
Fiorella Galello, Constanza Pautasso, Sol Reca, Luciana Cañonero, Paula Portela, Silvia Moreno, Silvia Rossi
Yeast cells can adapt their growth in response to the nutritional environment. Glucose is the favorite carbon source of Saccharomyces cerevisiae that prefers a fermentative metabolism despite the presence of oxygen. When glucose is consumed, the cell switches to the aerobic metabolism of ethanol, during the so-called diauxic shift. The difference between fermentative and aerobic growth is in part mediated by a regulatory mechanism called glucose repression. During glucose derepression a profound gene transcriptional reprogramming occurs and genes involved in the utilization of alternative carbon sources are expressed...
August 15, 2017: Yeast
https://www.readbyqxmd.com/read/28812258/chromosomal-flhb1-gene-of-the-alphaproteobacterium-azospirillum-brasilense-sp245-is-essential-for-correct-assembly-of-both-constitutive-polar-flagellum-and-inducible-lateral-flagella
#15
Yulia Filip'echeva, Andrei Shelud'ko, Alexei Prilipov, Elizaveta Telesheva, Dmitry Mokeev, Andrei Burov, Lilia Petrova, Elena Katsy
Azospirillum brasilense has the ability of swimming and swarming motility owing to the work of a constitutive polar flagellum and inducible lateral flagella, respectively. The interplay between these flagellar systems is poorly understood. One of the key elements of the flagellar export apparatus is the protein FlhB. Two predicted flhB genes are present in the genome of A. brasilense Sp245 (accession nos. HE577327-HE577333). Experimental evidence obtained here indicates that the chromosomal coding sequence (CDS) AZOBR_150177 (flhB1) of Sp245 is essential for the production of both types of flagella...
August 15, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#16
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811946/are-all-mutations-the-same-a-rare-case-report-of-coexisting-mutually-exclusive-kras-and-braf-mutations-in-a-patient-with-metastatic-colon-adenocarcinoma
#17
Anusha Vittal, Akshay Middinti, Anup Kasi Loknath Kumar
29-year-old Hispanic woman presented to the clinic with complaints of abdominal pain, nausea, fatigue, and constipation. Laboratory tests indicated the presence of iron deficiency anemia and transaminitis. Imaging evaluation revealed marked hepatomegaly with multiple hepatic metastases and pelvic lymphadenopathy. Biopsy of the hepatic lesions showed adenocarcinoma positive for pan-cytokeratin, CMA5.2, villin, and CDX2. She was positive for tumor markers CA 19-9, CA-125, and CEA. Upon further evaluation, she was found to have colorectal cancer positive for KRAS and BRAF mutations...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28811900/slpi-and-anxa2-expression-in-neoplasm-free-palatine-tonsils-is-associated-with-smoking-habit-of-individuals
#18
Elgar S Quabius, Berit Bögershausen, Lukas Getzin, Tibor Görögh, Maximilian P Gebhard, Anna S Hoffmann, Markus Hoffmann
In order to confirm the inverse correlation between secretory leucocyte protease inhibitor (SLPI) expression, and human papillomavirus (HPV) infection previously observed in head and neck squamous-cell carcinoma, the present study retrospectively investigated the association between SLPI and Annexin A2 (AnxA2) expression, and HPV status in non-neoplastic chronic tonsillitis (n=118), and tonsillar hyperplasia (n=96) tissue. We hypothesised that smoking induces the upregulation of SLPI, resulting in reduced binding of HPV to AnxA2, a known modulator of HPV entry into the cell...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28811867/modulation-of-glutathione-hemostasis-by-inhibition-of-12-15-lipoxygenase-prevents-ros-mediated-cell-death-after-hepatic-ischemia-and-reperfusion
#19
Moritz Drefs, Michael N Thomas, Markus Guba, Martin K Angele, Jens Werner, Marcus Conrad, Christian J Steib, Lesca M Holdt, Joachim Andrassy, Andrej Khandoga, Markus Rentsch
BACKGROUND: Reactive oxygen species- (ROS-) mediated ischemia-reperfusion injury (IRI) detrimentally impacts liver transplantation and resection. 12/15-Lipoxygenase (12/15-LOX), an antagonistic protein of the glutathione peroxidase 4 (GPX4) signaling cascade, was proven to mediate cell death in postischemic cerebral and myocardial tissue. The aim of this study was to investigate the impact of 12/15-LOX inhibition on hepatic IRI. METHODS: Livers of C57BL/6 mice were exposed to 60 minutes of partial warm ischemia and 90 minutes of reperfusion after previous Baicalein administration, an inhibitor of 12/15-LOX...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811666/the-essential-kinase-atr-ensuring-faithful-duplication-of-a-challenging-genome
#20
REVIEW
Joshua C Saldivar, David Cortez, Karlene A Cimprich
One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells...
August 16, 2017: Nature Reviews. Molecular Cell Biology
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