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https://www.readbyqxmd.com/read/28102733/plk1-polo-like-kinase-1-inhibits-mtor-complex-1-and-promotes-autophagy
#1
Stefanie Ruf, Alexander Martin Heberle, Miriam Langelaar-Makkinje, Sara Gelino, Deepti Wilkinson, Carolin Gerbeth, Jennifer Jasmin Schwarz, Birgit Holzwarth, Bettina Warscheid, Chris Meisinger, Marcel A T M van Vugt, Ralf Baumeister, Malene Hansen, Kathrin Thedieck
Mechanistic target of rapamycin complex 1 (MTORC1) and PLK1 (polo like kinase 1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28100806/the-lateral-line-confers-evolutionarily-derived-sleep-loss-in-the-mexican-cavefish
#2
James Jaggard, Beatriz G Robinson, Bethany A Stahl, Ian Oh, Pavel Masek, Masato Yoshizawa, Alex C Keene
Sleep is an essential behavior exhibited by nearly all animals, and disruption of this process is associated with an array of physiological and behavioral deficits. Sleep is defined by changes in sensory gating that reduce sensory input to the brain, but little is known about the neural basis for interactions between sleep and sensory processing. Blind Mexican cavefish comprise an extant surface dwelling form and 29 cave morphs that have independently evolved increased numbers of mechanoreceptive lateral line neuromasts and convergent evolution of sleep loss...
January 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28100803/a-new-cue-for-torpor-induction-charcoal-ash-and-smoke
#3
Clare Stawski, Julia Nowack, Gerhard Körtner, Fritz Geiser
Recent work has shown that the use of torpor for energy conservation increases after forest fires in heterothermic mammals, probably in response to the reduction of food. However, the specific environmental cues for this increased torpor expression remain unknown. It is possible that smoke and the novel substrate of charcoal and ash act as signals for an impending period of starvation requiring torpor. We therefore tested the hypothesis that the combined cues of smoke, a charcoal/ash substrate and food shortage will enhance torpor expression in a small forest-dwelling marsupial, the yellow-footed antechinus (Antechinus flavipes), because like other animals that live in fire-prone habitats they must effectively respond to fires to ensure survival...
January 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28100786/inositol-depletion-induced-by-acute-treatment-of-the-bipolar-disorder-drug-valproate-increases-levels-of-phytosphingosine
#4
Shyamalagauri Jadhav, Sarah Russo, L Ashley Cowart, Miriam L Greenberg
Bipolar disorder (BD) is a severe psychiatric illness affecting ~2% of the world population. Valproate (VPA) and lithium, though widely used for the treatment of BD, are not universally effective. These drugs have been shown to cause inositol depletion, but translating this observation to a specific therapeutic mechanism has been difficult, hampering the development of more effective therapies. We have shown previously in yeast that chronic VPA treatment induces the unfolded protein response due to increasing ceramide levels...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28099006/constituents-of-the-rhizomes-of-boesenbergia-pandurata-and-their-antiausterity-activities-against-the-panc-1-human-pancreatic-cancer-line
#5
Nhan Trung Nguyen, Mai Thanh Thi Nguyen, Hai Xuan Nguyen, Phu Hoang Dang, Dya Fita Dibwe, Hiroyasu Esumi, Suresh Awale
Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 6...
January 18, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28096445/unraveling-the-stereochemical-and-dynamic-aspects-of-the-catalytic-site-of-bacterial-peptidyl-trna-hydrolase
#6
Ashish Kabra, Salman Shahid, Ravi Kant Pal, Rahul Yadav, S V S Rama Krishna Pulavarti, Anupam Jain, Sarita Tripathi, Ashish Arora
Bacterial peptidyl-tRNA hydrolase (Pth; EC 3.1.1.29) hydrolyzes the peptidyl-tRNAs accumulated in the cytoplasm and thereby prevents cell death by alleviating tRNA starvation. X-ray and NMR studies of Vibrio cholerae Pth (VcPth) and mutants of its key residues involved in catalysis show that the activity and selectivity of the protein depends on the stereochemistry and dynamics of residues H24, D97, N118, and N14. D97-H24 interaction is critical for activity because it increases the nucleophilicity of H24. The N118 and N14 have orthogonally competing interactions with H24, both of which reduce the nucleophilicity of H24 and are likely to be offset by positioning of a peptidyl-tRNA substrate...
February 2017: RNA
https://www.readbyqxmd.com/read/28096443/stem-loop-rna-labeling-can-affect-nuclear-and-cytoplasmic-mrna-processing
#7
Stephanie Heinrich, Corinne L Sidler, Claus M Azzalin, Karsten Weis
The binding of sequence-specific RNA-interacting proteins, such as the bacteriophage MS2 or PP7 coat proteins, to their corresponding target sequences has been extremely useful and widely used to visualize single mRNAs in vivo. However, introduction of MS2 stem-loops into yeast mRNAs has recently been shown to lead to the accumulation of RNA fragments, suggesting that the loops impair mRNA decay. This result was questioned, because fragment occurrence was mainly assessed using ensemble methods, and their cellular localization and its implications had not been addressed on a single transcript level...
February 2017: RNA
https://www.readbyqxmd.com/read/28096404/torc1-dependent-sumoylation-of-rpc82-promotes-rna-polymerase-iii-assembly-and-activity
#8
Pierre Chymkowitch, Aurélie Nguéa P, Håvard Aanes, Joseph Robertson, Arne Klungland, Jorrit M Enserink
Maintaining cellular homeostasis under changing nutrient conditions is essential for the growth and development of all organisms. The mechanisms that maintain homeostasis upon loss of nutrient supply are not well understood. By mapping the SUMO proteome in Saccharomyces cerevisiae, we discovered a specific set of differentially sumoylated proteins mainly involved in transcription. RNA polymerase III (RNAPIII) components, including Rpc53, Rpc82, and Ret1, are particularly prominent nutrient-dependent SUMO targets...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096186/translation-reprogramming-is-an-evolutionarily-conserved-driver-of-phenotypic-plasticity-and-therapeutic-resistance-in-melanoma
#9
Paola Falletta, Luis Sanchez-Del-Campo, Jagat Chauhan, Maike Effern, Amy Kenyon, Christopher J Kershaw, Robert Siddaway, Richard Lisle, Rasmus Freter, Matthew J Daniels, Xin Lu, Thomas Tüting, Mark Middleton, Francesca M Buffa, Anne E Willis, Graham Pavitt, Ze'ev A Ronai, Tatjana Sauka-Spengler, Michael Hölzel, Colin R Goding
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood...
January 17, 2017: Genes & Development
https://www.readbyqxmd.com/read/28095488/metabolism-of-seriola-lalandi-during-starvation-as-revealed-by-fatty-acid-analysis-and-compound-specific-analysis-of-stable-isotopes-within-amino-acids
#10
Fernando Barreto-Curiel, Ulfert Focken, Louis R D'Abramo, María Teresa Viana
Fish starvation is defined as food deprivation for a long period of time, such that physiological processes become confined to basal metabolism. Starvation provides insights in physiological processes without interference from unknown factors in digestion and nutrient absorption occurring in fed state. Juveniles of amberjack Seriola lalandi were isotopically equilibrated to a formulated diet for 60 days. One treatment consisted of fish that continued to be fed and fish in the other treatment were not fed for 35 days...
2017: PloS One
https://www.readbyqxmd.com/read/28093985/ketogenic-diet-and-other-dietary-intervention-strategies-in-the-treatment-of-cancer
#11
Matteo Vergati, Eriseld Krasniqi, Girolamo Del Monte, Silvia Riondino, Doriana Vallone, Fiorella Guadagni, Patrizia Ferroni, Mario Roselli
Pre-clinical and clinical studies have investigated the role of a dysregulated metabolism in the sustainability of tumor initiation and progression. One of the most familiar metabolic alterations encountered in several types of cancers is the upregulation of glycolysis, which is also maintained in conditions of normal oxygen tension (aerobic glycolysis, Warburg effect) while oxidative phosphorylation is apparently reduced. As a result, cancer cells convert most incoming glucose to lactate. Although more rapid, adenosine triphosphate (ATP) production by glycolysis is less efficient in terms of ATP generated per unit of glucose consumed than oxidative phosphorylation...
January 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28093673/metagenomic-insights-into-effects-of-spent-engine-oil-perturbation-on-the-microbial-community-composition-and-function-in-a-tropical-agricultural-soil
#12
Lateef B Salam, Sunday O Obayori, Francisca O Nwaokorie, Aisha Suleiman, Raheemat Mustapha
Analyzing the microbial community structure and functions become imperative for ecological processes. To understand the impact of spent engine oil (SEO) contamination on microbial community structure of an agricultural soil, soil microcosms designated 1S (agricultural soil) and AB1 (agricultural soil polluted with SEO) were set up. Metagenomic DNA extracted from the soil microcosms and sequenced using Miseq Illumina sequencing were analyzed for their taxonomic and functional properties. Taxonomic profiling of the two microcosms by MG-RAST revealed the dominance of Actinobacteria (23...
January 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28090774/biakamides-a-d-unique-polyketides-from-a-marine-sponge-act-as-selective-growth-inhibitors-of-tumor-cells-adapted-to-nutrient-starvation
#13
Naoyuki Kotoku, Ryosuke Ishida, Hirokazu Matsumoto, Masayoshi Arai, Kazunari Toda, Andi Setiawan, Osamu Muraoka, Motomasa Kobayashi
Biakamides A-D, novel unusually unique polyketides, were isolated from an Indonesian marine sponge (Petrosaspongia sp.) with a constructed bioassay using PANC-1 human pancreatic cancer cells. Through detailed analyses of the one- and two-dimensional nuclear magnetic resonance (NMR) spectra of biakamides, planar chemical structures possessing a terminal thiazole, two N-methyl amides, a chloromethylene, and a substituted butyryl moiety were obtained. After elucidation of the configuration of the secondary alcohol moiety in biakamides A and B, the absolute stereostructures of the two secondary methyl groups in biakamides A-D were determined by the asymmetric total syntheses of all possible stereoisomers from the optically pure monoprotected 2,4-dimethyl-1,5-diol...
January 16, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28088480/sensing-membrane-curvature-in-macroautophagy
#14
REVIEW
Nathan Nguyen, Vladimir Shteyn, Thomas J Melia
In response to intracellular stress events ranging from starvation to pathogen invasion, the cell activates one or more forms of macroautophagy. The key event in these related pathways is the de novo formation of a new organelle called the autophagosome, which surrounds and sequesters either random portions of the cytoplasm or selectively targets individual intracellular challenges. Thus the autophagosome is a flexible membrane platform with dimensions that ultimately depend upon the target cargo. The intermediate membrane, termed the phagophore or isolation membrane, is a cup-like structure with a clear concave face and a highly curved rim...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#15
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28081189/global-gene-expression-analysis-of-cross-protected-phenotype-of-pectobacterium-atrosepticum
#16
Vladimir Gorshkov, Stanford Kwenda, Olga Petrova, Elena Osipova, Yuri Gogolev, Lucy N Moleleki
The ability to adapt to adverse conditions permits many bacterial species to be virtually ubiquitous and survive in a variety of ecological niches. This ability is of particular importance for many plant pathogenic bacteria that should be able to exist, except for their host plants, in different environments e.g. soil, water, insect-vectors etc. Under some of these conditions, bacteria encounter absence of nutrients and persist, acquiring new properties related to resistance to a variety of stress factors (cross-protection)...
2017: PloS One
https://www.readbyqxmd.com/read/28079880/nonradioactive-quantification-of-autophagic-protein-degradation-with-l-azidohomoalanine-labeling
#17
Jigang Wang, Jianbin Zhang, Yew Mun Lee, Shukie Ng, Yin Shi, Zi-Chun Hua, Qingsong Lin, Han-Ming Shen
At present, several assays that use radioisotope labeling to quantify the degradation of long-lived proteins have been developed to measure autophagic flux. Here, we describe a nonradioactive pulse-chase protocol using L-azidohomoalanine (AHA) labeling to quantify long-lived protein degradation during autophagy. AHA is used as a surrogate for L-methionine, and, when added to cultured cells grown in methionine-free medium, AHA is incorporated into proteins during de novo protein synthesis. After a chase period to remove short-lived proteins, autophagy is induced by starvation or other stimuli...
December 2017: Nature Protocols
https://www.readbyqxmd.com/read/28078580/in-vitro-evaluation-of-the-apoptosis-function-in-human-activated-t-cells
#18
Aude Magerus-Chatinet, Frédéric Rieux-Laucat
The apoptosis function can be monitored on human lymphocytes by quantifying the induced-death upon apoptotic stimuli involving either the extrinsic or the intrinsic pathway on in vitro activated T cells. Her, we describe an in vitro assay allowing the monitoring of three different apoptosis pathways: (1) the FAS-induced pathway, (2) the activation-induced cell death (AICD), and (3) the death induced by starvation of the cells, called activated-cell autonomous death (ACAD).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28077952/the-irr1-scc3-protein-implicated-in-chromosome-segregation-in-saccharomyces-cerevisiae-has-a-dual-nuclear-cytoplasmic-localization
#19
Piotr Kowalec, Jan Fronk, Anna Kurlandzka
BACKGROUND: Correct chromosome segregation depends on the sister chromatid cohesion complex. The essential, evolutionarily conserved regulatory protein Irr1/Scc3, is responsible for the complex loading onto DNA and for its removal. We found that, unexpectedly, Irr1 is present not only in the nucleus but also in the cytoplasm. RESULTS: We show that Irr1 protein is enriched in the cytoplasm upon arrest of yeast cells in G1 phase following nitrogen starvation, diauxic shift or α-factor action, and also during normal cell cycle...
2017: Cell Division
https://www.readbyqxmd.com/read/28077876/microenvironmental-autophagy-promotes-tumour-growth
#20
Nadja S Katheder, Rojyar Khezri, Fergal O'Farrell, Sebastian W Schultz, Ashish Jain, Mohammed M Rahman, Kay O Schink, Theodossis A Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark, Tor Erik Rusten
As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment...
January 19, 2017: Nature
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