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Cell LineCells, Cultured3T3 CellsTumor Cells, CulturedCell MembraneSubcellular FractionsCell Line, TumorCell NucleusCytosolFibroblastsMyocardiumBrainHeLa CellsNeuronsMuscle, Smooth, VascularCHO CellsBlood PlateletsPC12 CellsCOS CellsCytoplasmEpithelial CellsEndothelium, VascularLiver
Rats, Sprague-DawleyCattleRabbitsCricetinaeRats, WistarMice, KnockoutMice, Inbred C57BL
Chemicals and Drugs164
Protein Kinase C-alphaProtein Kinase CIsoenzymesTetradecanoylphorbol AcetateProtein Kinase C betaProtein KinasesPhorbol 12,13-DibutyrateProtein Kinase C-deltaProtein Kinase C-epsilonDiglyceridesCyclic AMP-Dependent Protein KinasesPhospholipase DCarbazolesEnzyme InhibitorsIndolesCalcium-Calmodulin-Dependent Protein KinasesCalciumProtein-Serine-Threonine KinasesMitogen-Activated Protein KinasesProtein Kinase InhibitorsPhosphatidylinositol 3-KinasesPhorbol Estersp38 Mitogen-Activated Protein KinasesRecombinant ProteinsMitogen-Activated Protein Kinase 1AlkaloidsRNA, Messenger1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineStaurosporineMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase KinasesJNK Mitogen-Activated Protein KinasesMaleimidesBenzophenanthridinesIsoquinolinesCyclic AMPProtein-Tyrosine KinasesPhosphatidylserinesPhenanthridinesAMP-Activated Protein Kinasessrc-Family KinasesSerineCyclic GMP-Dependent Protein KinasesPhosphoproteinsCasein Kinase IICalcium-Calmodulin-Dependent Protein Kinase Type 2Type C PhospholipasesCDC2 Protein KinaseIntracellular Signaling Peptides and ProteinsExtracellular Signal-Regulated MAP KinasesMAP Kinase Kinase KinasesProto-Oncogene ProteinsBryostatinsPhosphoprotein PhosphatasesMAP Kinase Kinase 1Recombinant Fusion ProteinseIF-2 KinaseProto-Oncogene Proteins c-aktCyclic AMP-Dependent Protein Kinase Type IIRibosomal Protein S6 KinasesTyrosinep21-Activated KinasesThreonineDiacylglycerol KinaseCasein KinasesCarrier ProteinsMembrane ProteinsPhosphoserineMAP Kinase Kinase 4ProteinsNaphthalenesPhosphotransferases (Alcohol Group Acceptor)Enzyme ActivatorsAdenosine TriphosphateFlavonoids3-Phosphoinositide-Dependent Protein KinasesPiperazinesCyclin-Dependent KinasesIonomycinAndrostadienesDNAPeptidesCalcimycinGlycogen Synthase Kinase 3Receptors, Adrenergic, alphaDNA-Binding Proteinsrho-Associated KinasesSphingosinePhosphatidylinositolsGlyceridesTranscription Factorsalpha 1-AntitrypsinCalmodulinGTP-Binding ProteinsColforsinPyridinesReceptor Protein-Tyrosine KinasesCreatine KinaseImidazolesChromonesEpidermal Growth FactorMacromolecular SubstancesDNA PrimersAcetophenonesDNA-Activated Protein KinaseProtein IsoformsOkadaic AcidNF-kappa BPyruvate KinaseI-kappa B KinaseMorpholinesPhosphopeptidesProtein Phosphatase 18-Bromo Cyclic Adenosine MonophosphateRNA, Small InterferingMyosin-Light-Chain KinaseMAP Kinase Kinase Kinase 1InsulinHypoxia-Inducible Factor 1, alpha SubunitPhosphothreoninePeptide FragmentsMitogen-Activated Protein Kinase 8Nuclear ProteinsRibosomal Protein S6 Kinases, 90-kDaReceptors, Adrenergic, alpha-1Tumor Necrosis Factor-alphaBenzopyransA Kinase Anchor ProteinsMAP Kinase Kinase 2DNA, ComplementaryFocal Adhesion Kinase 1GlucoseInositol PhosphatesCell Cycle ProteinsProtein Phosphatase 2Pertussis Toxin1-Phosphatidylinositol 4-KinaseProto-Oncogene Proteins c-rafAdaptor Proteins, Signal TransducingButadienesCDC2-CDC28 KinasesThymidine KinaseArachidonic AcidFocal Adhesion Protein-Tyrosine KinasesCyclic GMPSulfonamidesVirulence Factors, BordetellaEgtazic AcidMitogen-Activated Protein Kinase 14GenisteinPhosphotyrosineLactonesCarcinogensThionucleotidesReceptors, Cell SurfaceAurora KinasesNerve Tissue ProteinsCarbacholBombesinMultienzyme ComplexesReceptor, Epidermal Growth FactorActinsPhorbolsTOR Serine-Threonine Kinases
Analytical, Diagnostic and Therapeutic Techniques and Equipment15
TransfectionBlotting, WesternImmunoblottingCloning, MolecularElectrophoresis, Polyacrylamide GelPeptide MappingModels, BiologicalMutagenesis, Site-DirectedPrecipitin TestsBlotting, NorthernModels, MolecularReverse Transcriptase Polymerase Chain ReactionMicroscopy, FluorescenceSequence AlignmentImmunohistochemistry
Phenomena and Processes42
Enzyme ActivationPhosphorylationSignal TransductionTransfectionAmino Acid SequenceMAP Kinase Signaling SystemDown-RegulationProtein BindingGene Expression Regulation, EnzymologicBase SequenceProtein TransportKineticsDose-Response Relationship, DrugCell DivisionApoptosisMutagenesisBinding SitesSubstrate SpecificityMutationGene Expression RegulationTime FactorsProtein Structure, TertiaryTranscription, GeneticSequence Homology, Amino AcidGene ExpressionSecond Messenger SystemsMolecular WeightCell DifferentiationBiological TransportStructure-Activity RelationshipUp-RegulationProtein ConformationPromoter Regions, GeneticCell SurvivalProtein Processing, Post-TranslationalCell CycleCell ProliferationEnzyme InductionPlasmidsCatalysisCell MovementTranscriptional Activation
Molecular Sequence DataAmino Acid SequenceBase Sequence
AnatomyOrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
Protein Kinase C-alphaProtein Kinase CIsoenzymesTetradecanoylphorbol AcetateProtein Kinase C betaEnzyme ActivationProtein KinasesPhorbol 12,13-DibutyratePhosphorylationProtein Kinase C-deltaProtein Kinase C-epsilonDiglyceridesSignal TransductionCyclic AMP-Dependent Protein KinasesPhospholipase DCarbazolesEnzyme InhibitorsIndolesMolecular Sequence DataCalcium-Calmodulin-Dependent Protein KinasesCell LineCells, CulturedCalciumProtein-Serine-Threonine KinasesTransfectionMitogen-Activated Protein KinasesAmino Acid Sequence3T3 CellsProtein Kinase InhibitorsBlotting, WesternTumor Cells, CulturedPhosphatidylinositol 3-KinasesMAP Kinase Signaling SystemPhorbol EstersDown-Regulationp38 Mitogen-Activated Protein KinasesProtein BindingGene Expression Regulation, EnzymologicBase SequenceRecombinant ProteinsCell MembraneMitogen-Activated Protein Kinase 1Protein TransportSubcellular FractionsAlkaloidsRNA, Messenger1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineKineticsStaurosporineCell Line, TumorMitogen-Activated Protein Kinase 3Dose-Response Relationship, DrugMitogen-Activated Protein Kinase KinasesCell DivisionCell NucleusJNK Mitogen-Activated Protein KinasesMaleimidesBenzophenanthridinesIsoquinolinesCyclic AMPProtein-Tyrosine KinasesApoptosisPhosphatidylserinesPhenanthridinesAMP-Activated Protein Kinasessrc-Family KinasesSerineCyclic GMP-Dependent Protein KinasesMutagenesisPhosphoproteinsBinding SitesSubstrate SpecificityCytosolCasein Kinase IIMutationCalcium-Calmodulin-Dependent Protein Kinase Type 2Type C PhospholipasesCDC2 Protein KinaseRats, Sprague-DawleyIntracellular Signaling Peptides and ProteinsGene Expression RegulationExtracellular Signal-Regulated MAP KinasesMAP Kinase Kinase KinasesProto-Oncogene ProteinsCattleBryostatinsPhosphoprotein PhosphatasesTime FactorsMAP Kinase Kinase 1Recombinant Fusion ProteinseIF-2 KinaseProto-Oncogene Proteins c-aktCyclic AMP-Dependent Protein Kinase Type IIRibosomal Protein S6 KinasesProtein Structure, TertiaryTranscription, GeneticImmunoblottingTyrosinep21-Activated KinasesCloning, Molecular
Protein Kinase C-alpha
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
Protein Kinase C
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Isoenzymes
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Tetradecanoylphorbol Acetate
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Protein Kinase C beta
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Enzyme Activation
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Phorbol 12,13-Dibutyrate
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Protein Kinase C-delta
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Protein Kinase C-epsilon
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
Diglycerides
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cyclic AMP-Dependent Protein Kinases
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Phospholipase D
An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.
Carbazoles
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Indoles
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Calcium-Calmodulin-Dependent Protein Kinases
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Established cell cultures that have the potential to propagate indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Protein-Serine-Threonine Kinases
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Mitogen-Activated Protein Kinases
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
3T3 Cells
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Agents that inhibit PROTEIN KINASES.
Blotting, Western
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Tumor Cells, Cultured
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Phosphatidylinositol 3-Kinases
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
MAP Kinase Signaling System
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Phorbol Esters
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
Down-Regulation
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
p38 Mitogen-Activated Protein Kinases
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Gene Expression Regulation, Enzymologic
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins prepared by recombinant DNA technology.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Mitogen-Activated Protein Kinase 1
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Protein Transport
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Subcellular Fractions
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
The rate dynamics in chemical or physical systems.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
Cell Line, Tumor
A cell line derived from cultured tumor cells.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
Dose-Response Relationship, Drug
The relationship between the dose of an administered drug and the response of the organism to the drug.
Mitogen-Activated Protein Kinase Kinases
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
JNK Mitogen-Activated Protein Kinases
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Maleimides
Benzophenanthridines
Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.
Isoquinolines
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
Cyclic AMP
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Protein-Tyrosine Kinases
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Phosphatidylserines
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
Phenanthridines
AMP-Activated Protein Kinases
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
src-Family Kinases
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Cyclic GMP-Dependent Protein Kinases
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Phosphoproteins
Binding Sites
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Substrate Specificity
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Casein Kinase II
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Calcium-Calmodulin-Dependent Protein Kinase Type 2
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Type C Phospholipases
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
CDC2 Protein Kinase
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Intracellular Signaling Peptides and Proteins
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Extracellular Signal-Regulated MAP Kinases
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
MAP Kinase Kinase Kinases
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Bryostatins
A group of 20-member macrolactones in which there are three remotely substituted pyran rings that are linked by a methylene bridge and an E-disubstituted alkene, and have geminal dimethyls at C8 and C18 carbons. Some interact with PROTEIN KINASE C.
Phosphoprotein Phosphatases
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
Elements of limited time intervals, contributing to particular results or situations.
MAP Kinase Kinase 1
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Recombinant Fusion Proteins
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
eIF-2 Kinase
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Proto-Oncogene Proteins c-akt
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Cyclic AMP-Dependent Protein Kinase Type II
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
Ribosomal Protein S6 Kinases
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Transcription, Genetic
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Immunoblotting
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
p21-Activated Kinases
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
Cloning, Molecular
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Sequence Homology, Amino Acid
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
Casein Kinases
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
Transport proteins that carry specific substances in the blood or across cell membranes.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Electrophoresis, Polyacrylamide Gel
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Phosphoserine
The phosphoric acid ester of serine.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Naphthalenes
Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
Peptide Mapping
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Phosphotransferases (Alcohol Group Acceptor)
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Enzyme Activators
Compounds or factors that act on a specific enzyme to increase its activity.
Adenosine Triphosphate
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A group of phenyl benzopyrans named for having structures like FLAVONES.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
3-Phosphoinositide-Dependent Protein Kinases
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
Cyclin-Dependent Kinases
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
Mutagenesis, Site-Directed
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Ionomycin
A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.
Androstadienes
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Receptors, Adrenergic, alpha
One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.
DNA-Binding Proteins
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
rho-Associated Kinases
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
Sphingosine
An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)
Phosphatidylinositols
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
Glycerides
GLYCEROL esterified with FATTY ACIDS.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Second Messenger Systems
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Cricetinae
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
The sum of the weight of all the atoms in a molecule.
alpha 1-Antitrypsin
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
GTP-Binding Proteins
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
Colforsin
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
Pyridines
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Receptor Protein-Tyrosine Kinases
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Creatine Kinase
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
Imidazoles
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Rats, Wistar
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
Macromolecular Substances
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
DNA Primers
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Acetophenones
Biological Transport
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
Mice, Knockout
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
DNA-Activated Protein Kinase
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Protein Isoforms
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Structure-Activity Relationship
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Up-Regulation
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Okadaic Acid
A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)
NF-kappa B
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Pyruvate Kinase
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
I-kappa B Kinase
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
Morpholines
Phosphopeptides
Protein Phosphatase 1
A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.
8-Bromo Cyclic Adenosine Monophosphate
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Myosin-Light-Chain Kinase
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
MAP Kinase Kinase Kinase 1
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
Promoter Regions, Genetic
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Blotting, Northern
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Hypoxia-Inducible Factor 1, alpha Subunit
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
Phosphothreonine
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
Peptide Fragments
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Cell Survival
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Nuclear Proteins
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Ribosomal Protein S6 Kinases, 90-kDa
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Muscle, Smooth, Vascular
The nonstriated involuntary muscle tissue of blood vessels.
Receptors, Adrenergic, alpha-1
A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.
Tumor Necrosis Factor-alpha
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Benzopyrans
Compounds with a core of fused benzo-pyran rings.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A Kinase Anchor Proteins
A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
DNA, Complementary
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Focal Adhesion Kinase 1
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
Inositol Phosphates
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.


text:
Featured Test Prep Student: Sam Hunt
Featured Student | SAT Prep
For 17-year-old Sam Hunt, balancing a busy schedule and finding time to prepare for the SAT was a challenge. His college counselor recommended that he sign up for a test prep program with A+ Test Prep and Tutoring.
"At first, my biggest fear was that the program would add extra stress to the whole process," he remembered.
However, the rising senior from Wissahickon High School soon learned that spending dedicated time focusing on the test was just what he needed.
His mother, Lisa Hunt, evaluated the options and determined that one-to-one tutoring with A+ could be a great fit. "I really wanted it to be time well spent," she said, noting that with group classes, he might not get the maximum benefits of a tutoring program. "His schedule was just so crazy. I wanted him to make the most of time he did have," she said.
Sam entered a full test prep program, meeting at his home with tutors Elizabeth Sweger for the verbal portions and Daniel McDowell for math. Since Sam typically excels in math, A+ customized his program so that more sessions were spent on his (relatively) weaker areas: Critical Reading and Writing.
Sam found that his tutors were personable and kept expectations realistic.
"Finding a balance between the tutoring homework, schoolwork, and extracurricular activities was difficult," Sam explained. "My tutors kept in mind that I had other very large commitments." He plays varsity and club soccer, is a member of Future Business Leaders of America, and enjoys snowboarding.
Sam learned test-taking strategies that helped him improve little by little throughout his time in the program. He was answering most questions correctly in the Math section, for example, but McDowell helped him fine-tune his approach by helping him determine how many questions he should skip, and which ones he should answer.
On the verbal side, Sam found the content more challenging. Sweger was able to teach him to "think like the test makers" and understand how to pick a right answer, even if he wasn't sure how to answer a question.
"One of the things I believe helped Sam most was practice," Sweger said. "Not only did it help him become a more flexible test taker who could adjust his approach depending on what types of sentences or passages he encountered, but it also helped him identify areas in need of improvement.
"Providing Sam with vocabulary lists, practice passages, sample essays, and advice from a variety of sources enhanced Sam's knowledge and comfort with the test so that he could achieve his goals," she said.
Sam took the SAT three times and improved his score each time. He attributes his continual improvement to taking practice tests and focusing on the Critical Reading section. His attitude toward the test also changed throughout the process and impacted his scores positively. "It was really about confidence for me," he said. "Learning to 'like' the sections was difficult, considering I just wanted the test to be over at the beginning. I changed my attitude, allowing myself to become way more 'excited' for some of the sections."
Sweger agreed that Sam had the right attitude. "He was never satisfied with doing less than his best and, as a result, he was able to make admirable progress."
After taking the January 2015 SAT, Sam took it again in March and saw a 230-point increase in his score. When he took the SAT again in June, his score jumped another 90 points.
"By the third test, I went in with an extremely prepared mindset, and I was ready to do well," Sam remembered.
Lisa concluded that the tutoring program was really worth the investment. "So much depends on the kid, but with our experience, the tutors really clicked with Sam and gave him what he needed," she said. "It was a positive experience. We have a daughter two years behind Sam, and we will look into using A+ again."
"If you want to succeed, you will," Sam concluded. "The sessions are what you make of them. If you don't do the homework and don't pay attention during the tutoring, it will be hard to improve."
With a strong SAT score under his belt, Sam looks toward college visits and applications. "I am looking to study business during college," he said. "My first choice is Bucknell, but I am also interested in Elon, American, and Maryland."
With his strong work ethic and willingness to put in the time, Sam is sure to be successful at the next level.
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The video also teases that you can do freeplay in the end-game.
Is this enough endgame content for you? In the second video from the This Is Anthem series, the team focuses on what players can expect from the endgame.
As you take on missions in Anthem, your Pilot level will increase, making new aspects of all your javelins available.
What's in store for Anthem players that reach Pilot Level 30? Challenges will award you with coins and crafting materials, while strongholds are team-required missions with some of the biggest rewards. Check out all the different options below. The last three are called Grandmaster 1, 2, and 3.
The higher the difficulty level, the better your chances of finding Anthem's highest rarity gear and personalization items. Seamless and intelligent matchmaking will ensure you can quickly and easily find other players to adventure alongside. Complete a variety of endgame missions, including contracts and challenges to unlock and gather all the pieces.
As you become a more powerful Freelancer, people in Fort Tarsis start to notice you more - and some of them would love to put you to work. Different factions will offer contracts: sometimes unpredictable missions with unique problems.
Legendary contracts will appear too, though these will be sectioned out into a few parts and a lot harder to complete... but just think of that sweet sweet loot at the end! They're called "the highest-level challenges" that are "longer missions" against "some of the deadliest enemies in the world", and they're rewarded with "some of the best loot in the game".


text:
Two-Headed Consumer Demands Change from Farmers, Food Companies
by Jennifer Shike
07:52AM Dec 05, 2019
Grocery Store Images
( Wyatt Bechtel )
A two-headed consumer strolls around today's grocery stores, confusing producers and retailers. One day a consumer searches out food products that are local, organic and welfare-friendly. The next week, that very same consumer chooses food items that are cheap, affordable and safe.
The challenge? This two-headed consumer doesn't behave the same way all the time.
It's puzzling to both farmers and food companies and is causing a huge shift in what retailers buy from farmers.
"Suddenly big is bad and food companies are really struggling with that new paradigm," says Aidan Connolly, chief executive officer of Cainthus and president of AgriTech Capital. "Before now, being big was good. You used to gain credibility by being associated with big brands."
But that's no longer true. Food companies are now trying to guess what consumers are looking for, tick more boxes and answer more questions than competitor companies. A new global survey on consumer expectations says consumers want farmers to be sustainable.
"Words like safe, healthy, local were words that used to come to the top of the list of what consumers wanted farmers to be," says Emily Johannes, director of sustainability for K-Coe Isum, referencing Cargill's survey. "Now they want us to be sustainable. They aren't saying they want us to all be organic or all plant-based protein – this is a huge opportunity for us to be who we want to be."
The prosumer's perspective
Today's consumer wants to know how their food is grown and raised. They are asking harder questions. The conversations are lasting longer. The stakes are getting higher.
"Prosumers are consumers who actively become involved with the design, production and delivery of the goods and services they consume, leveraging the power of social media to become vocal advocates for products and brands," Connolly says. "What they choose to consume reflects their values, aspirations and beliefs. From a food company's perspective, it means that prosumers increasingly shape, and even control, the message and drive demand – not the manufacturer."
For example, in Australia, farmers are advertising eggs based on the water footprint of the egg (this chicken used less water than its competitor). Connolly says this is just one example of issues driving farming practices that were never issues before.
"You're seeing questioning of farm practices like never before," Connolly says. "On a global scale, that's being reflected in what farmers are choosing to do."
Farmers in Europe, the United Kingdom and Ireland are under great pressure to know their carbon footprint and to demonstrate what practices they are engaged in to reduce it.
"I don't believe we should give in to their every whim, but we do need to interact with them. We need to find out what they want to know about us and what they are expecting from us," Johannes says. "It's pretty simple: Tell them what you are doing, how you are doing it and prove it."
Where do the food companies fit in?
The consumer's push for more sustainability in farming is forcing food companies to gather data that they have never had to pay attention to before, Johannes says. It's no longer just about cost, companies are looking at operational data and use.
"Companies must interact with their suppliers (first and foremost farmers)," she says. "Consumers want to know what's going on at the farm. The greatest opportunity for environmental stewardship is for companies to manage that activity. A physical four-wall plant has its impact, but not like hundreds of farmers supplying product to that plant."
Food companies can receive an unexpected benefit from this, Johannes adds. When consumers question how farmers do things, companies can step in and evaluate their farm suppliers' practices and find answers while mitigating future challenges.
This push is also resulting in food companies adjusting their product assortments in conjunction with food retailer and foodservice company partners, says Justin Sherrard, global protein strategist for Rabobank's Raboresearch Food and Agribusiness team.
Food companies are watching closely to where the consumer demand is growing, then determining quickly if there is an opportunity for the supply chain.
Graphic courtesy of Cargill
Does it make cents?
When it comes to pursuing sustainability, economics is everything, Johannes says. Sustainability is all about implementing continuous improvements in a business, so it has to make financial sense.
"Economics enables decisionmaking that we need to make a technology investment. We can't make those decisions lightly," she adds.
Sherrard says that technology is lacking when it comes to sustainability practices.
"We are going to see plenty of change in animal-based agriculture over the years ahead, and we need technology to be a part of that change," he says.
Livestock producers need to consider how technology can be implemented to improve productivity, reduce labor needs, help identify potential illness in the herd/flock, improve gut health and feed efficiency, provide an optimal environment for animal comfort, reduce risk of water pollution, and more, he says.
"There is much that technology can and should do in animal-based agriculture, but I feel we are lagging too far behind crop farmers when it comes to the development and deployment of technology," Sherrard adds.
Technology is a game changer for everyone in agriculture, Connolly says. However, there's often a resistance to change and distrust of where that change is coming from.
"A lot of times it feels these demands are not fair and are being pushed onto both farmers and those on the supply side. This probably reflects the fact that consumers don't understand farming. It's hard to accept what is being imposed and see the positive, but it's funny how often you can," Connolly says. "Before reacting negatively and saying why we can't do it, think about what can be done and in the end, is it actually good for business? Is it better for the people, animal, consumer and environment involved?"
Understanding the "S" word
A number of strategies can demonstrate a farmer's sustainability. Johannes encourages farmers to avoid getting caught up in the mishmash of terms such as regenerative agriculture or soil health.
Continue to page 2.
U.S. Trade With China Extends Decline as Tariff Talks Drag On
World Dairy Expo Names Official Judges for 2020 Show


Wishing all our customers a Happy Easter!!
Steve Wilson (Builder) recommended you to us and we ended up purchasing all materials from you to tile a bathroom and a downstairs hallway/kitchen area.
We just wanted to say thanks for an excellent and professional service to both Gary in the shop, and to Gavin the tiller (recommended by A&M) who did a first class installation job.
Gavin fully achieved our expectations in terms of the finished job, and I would gladly recommend his services to anyone. Kindly pass on our thanks when you see him next.


Hand & Body Salve for Extra Dry Skin – The Cascadia Soap Co.
A few decades ago, clients often asked us to create a product that would make their dry cracked heels soft and supple. We knew it would be a challenge, dealing with the thickest and often driest skin on the body! Thankfully, recipes for handcrafted salves and balms trace back in our European family for many generations.
We formulated our Hand & Body Salve for Extra Dry Skin by combining organic nut butter of the West African Shea tree with the right proportions of chamomile infused olive oil, vitamin E, lavender, and sweet orange essential oils for their combined healing, ultra moisturizing and soothing properties. We knew we had a winner! The verdict always comes from the customers... And it keeps coming in the form of phone calls, e-mails, letters, and conversations.
Use it daily on heels, elbows, knees, hands, cuticles and any extra dry, itchy spots on your body.


text:
BROOKFIELD, Wis., and CHICAGO, Nov. 18, 2015 – After a successful health system merger and subsequent rebranding in 2013, Chicago-based Presence Saint Joseph Hospital, part of Presence Health, has commenced operation in a new patient-centered outpatient facility in Chicago's Lincoln Park neighborhood. The Presence Center for Advanced Care celebrated its grand opening last month with a ribbon cutting and blessing from Chicago Archbishop Blase J. Cupich. Also involved was 44th Ward Alderman Tom Tunney, as was hospital leadership in the 10-story outpatient facility.
The lakefront medical facility has been developed and leased by leading healthcare consulting firm, Hammes Company, and is located on the hospital campus at the intersection of Surf Street and Sheridan Road.
"The Presence Center for Advanced Care will further enhance the exceptional, patient-centered care provided on our campus," says Roberta Luskin-Hawk, M.D., Presence Saint Joseph Hospital President and CEO.
"We focused on creating a healing environment with an emphasis on technology, convenience, access and superior outcomes. We have phenomenal physician and nursing teams and our newly expanded footprint will enhance the abilities of medical teams to more efficiently see patients in both outpatient and inpatient settings on one campus."
The building opened in September with a robust mix of services, including advanced diagnostics capabilities, ambulatory surgery, a full endoscopy center, laboratory services, physical therapy and rehabilitation, along with specialty services such bariatrics, orthopedics and comprehensive oncology services through the Mark M. Connolly Center for Cancer and Specialty Care. There is an advanced imaging center dedicated solely to women's services, providing low-dose 3D mammography, PET-CT and digital X-ray to patients. The facility houses three floors of physician office suites as well as three levels of indoor parking, and connects directly to the hospital via a glass sky bridge at 2900 N. Lake Shore Drive.
Hammes Partners, a healthcare real estate private equity firm affiliated with Hammes Company, provided development capital for the project and retains ownership of the facility.
"Hammes Partners is pleased to have invested in a facility that will serve the healthcare needs of the community for decades to come" says Todd Kibler, Principal of Hammes Partners.
"The conceptualization and implementation surrounding this project was truly a collaborative effort by a team composed of representatives from Presence, RTKL, Power Construction and various Hammes affiliated entities. We look forward to augmenting the existing tenancy with complementary outpatient services and physician practices in the medical office space," says Mr. Kibler.
The urban location services one of the most densely populated neighborhoods in Chicago, as the ambulatory center sits within walking distance of Lake Shore Drive, public transportation, restaurants, hotels, museums and the Lincoln Park Zoo.
"The development of the Presence Center for Advanced Care marks an exciting time for patients, leadership, staff and neighbors in a city that embraces a neighborhood model," says Richard Galling, Hammes Company President and COO. "We are thrilled to have partnered with Presence Saint Joseph Hospital on this innovative facility in Chicago."
In addition to Hammes Partners and Hammes Company, the project team includes architecture firm RTKL Associates Inc. and construction manager Power Construction, both of Chicago. Kirk Dunlap, Development Manager with Hammes Company, is leading all physician leasing efforts and can be contacted at kdunlap@hammesco.com or 262-792-5900. Leasing and custom build-out of physician suites on the three medical office floors has commenced, however there is still availability for new tenants.
About Hammes Company
Hammes Company comprises a team of accomplished professionals with deep industry and functional expertise. The company assists a full spectrum of healthcare clients by advising, implementing and managing key strategies and solutions that build high-performing organizations. Hammes Company is recognized by leading healthcare providers and industry insiders as one of the most trusted providers of consulting services in the United States. The company currently serves health systems, hospitals, physician groups and payers. Hammes Company is headquartered in Brookfield, Wis., and provides services through a network of regional offices strategically located across the country. For more information, please visit www.hammesco.com.
About Hammes Partners
Hammes Partners is a private equity firm focused exclusively on the U.S. healthcare real estate market. Hammes Partners is complemented by a suite of services offered by its affiliates, including Hammes Company Healthcare, a nationally recognized healthcare industry leader since 1993. The company is headquartered in Milwaukee, Wis. For more information, please visit www.hammespartners.com.
About Presence Saint Joseph Hospital
Presence Saint Joseph Hospital is an award-winning academic medical center on Chicago's north side overlooking the shores of Lake Michigan and Lincoln Park. Established in 1868, Presence Saint Joseph has grown with the community and is known for advanced care in cardiology, headache, cancer care, cardiac care, minimally invasive surgery, plastic surgery, neonatal care and treatment of HIV and its complications. Dedicated to delivering an exceptional patient experience, Presence Saint Joseph is recognized as one of the best hospitals in Chicago by U.S. News & World Report and was Chicago's only 2014 Truven Health Top 50 Cardiovascular Hospital. Training the next generation of physicians and other health care providers, Presence Saint Joseph has 600 physicians in more than 50 specialties on its medical staff, many who are locally or nationally recognized for their clinical expertise, innovative programs and academics. More information is available at http://www.presencehealth.org/presence-saint-joseph-hospital-chicago.
© Hammes Partners. All rights reserved.


text:
Hullabaloo é um filme estadunidense de 1940, do gênero comédia dirigido por Edwin L. Marin.

Elenco
 Frank Morgan… Frankie' Merriweather
 Virginia Grey… Laura Merriweather
 Dan Dailey… Bob Strong
 Billie Burke… Penny Merriweather
 Nydia Westman… Lulu Perkins

Filmes dos Estados Unidos de 1940
Filmes de comédia dos Estados Unidos
Filmes dirigidos por Edwin L. Marin
Filmes em língua inglesa

redpajama_set_name: RedPajamaWikipedia


text:
Q: meaning of - rite - at the companies names There is bunch of companies that use rite at theirs names, like Rite Aid or Shop Rite, I was thinking about it like
Right => Rite
They looks like similar to pronounce, and you could think Right Aid or Right Shop
but later on I found really meaning for rite that obviously makes the sense.
So I wonder what's the right meaning:) that usually native speakers keep in mind when they think about Rite Company?

A: When native speakers see "Rite Company," said Company would like the patron to think "Right," as in "correct" or "accurate," or maybe even "righteous."
There are no solemn ceremonies at Rite Aid or Shop Rite that would pass for a rite.
Dictionary.com defines rite as:

a formal or ceremonial act or procedure prescribed or customary in religious or other solemn use: rites of baptism; sacrificial rites.

(Although signing the disclosures for your prescription may be a formal act or procedure, there is no religious component.)

redpajama_set_name: RedPajamaStackExchange


American retail titan Sears has filed for bankruptcy as they cave under a $190 million debt.
With Christmas just weeks away, an expert has unveiled the secrets to hiring at the last minute.
A shake-up of Australia's recycling commitments has big implications for the retail sector.
Retail spending has tipped market expectations and registered an increase of 0.3 per cent in August.


Although many questions still remain about why so many patients perished at the center, one thing is certain—these four lawsuits are just the beginning of what is sure to be a lengthy investigation and legal battle for the nursing home.
If a loved one has suffered injury or death at the hands of nursing home staff, you may be able to recover through a negligence action. Contact the attorneys at Slappey & Sadd for a free consultation to discuss your case by calling 404.255.6677. We serve the entire state of Georgia, including the following locations: Atlanta, Roswell, and Sandy Springs.


text:
est le cinquième album studio du groupe de Black metal belge Enthroned. L'album est sorti en août 2002 sous le label Napalm Records. C'est le premier album du groupe sorti sous ce label.

C'est le premier album enregistré avec le batteur Alsvid.

Musiciens

 Lord Sabathan - vocal, basse
 Nornagest - guitare
 Nerath Daemon - guitare
 Alsvid - batterie

Liste des morceaux

 Boundless Demonication - 04:11
 Infernal Flesh Massacre - 04:17
 Spawn From The Abyss - 05:09
 Bloodline - 05:06
 Jehova Desecration - 02:27
 Diabolic Force - 03:22
 Land Of Demonic Fears - 01:30
 Radiance Of Mordacity - 03:40
 Graced By Evil Blood - 08:18
 Carnage In Worlds Beyond - 01:23

Album d'Enthroned
Album musical sorti en 2002
Album publié par Napalm Records
Album produit par Harris Johns


text:
EnerKnol Blog
White House Open Data Initiative identifies EnerKnol as a top innovator harnessing data to build U.S. clean energy economy. NEW YORK, May 28, 2014 /PRNewswire-iReach/ — EnerKnol today announced that the White House and the U.S. Department of Energy have selected the company to present its decision support technology at the 2014 White House Energy Datapalooza onWednesday,…...
EnerKnol Founder & CEO, Angelique Mercurio, will speak during the Closing Keynote at the 10th annual CIO Executive Summit happening in midtown Manhattan on May 13, 2014. Ms. Mercurio joins a lineup of leading technology and data executives from globally-recognized organizations such as Thomas Reuters, Colgate-Palmolive, GE, Moody's, and Dell who will be speaking at the…...
EnerKnol Selected as Semi-Finalist to Present at We Own It Summit Investor Showcase EnerKnol (formerly Energy Solutions Forum) has been selected as a semi-finalist in the We Own It Summit Global Venture Competition and will demo at the upcoming Investor Showcase in Philadelphia on May 1. The We Own It Summit brings together organizations, entrepreneurs,…...
EnerKnol Founder to speak at Wharton Innovation Summit EnerKnol (formerly Energy Solutions Forum) CEO and Founder, Angelique Mercurio, will speak Wednesday, April 30, at the inaugural Innovation Summit hosted by the Wharton Alumni Club of Washington, DC. The conference will bring together leaders in innovation across multiple industries to highlight tools and techniques that have…...
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The primary mission of the country's icebreakers has always been to ensure year-round navigability of the Northern Sea Route, which is used to deliver various oil and gas production equipment to Siberia and extract raw materials from the region.
The global race for the Arctic resources is now truly on. A Greenpeace mission has failed to storm Russia's Prirazlomnaya oilrig, Moscow is actively developing the Northern Sea Route infrastructure, and the United States will invest $8 billion in Arctic projects. Russia appears to be particularly well equipped for the mission with its fleet of unique icebreakers.
The primary mission of Russia's icebreakers has always been to ensure year-round navigability of the Northern Sea Route, which is used to deliver various oil and gas production equipment to Siberia and extract raw materials from the region.
The first such icebreaker, the nuclear-powered vessel Lenin, was built at Leningrad's Admiralteyskie Verfi Shipyard in 1959. An embodiment of the technical progress of her time, the Lenin comprised 70,000 parts, with the total length of welds stretching to more than 6,000 kilometer.
The second nuclear-powered icebreaker in the world, the Arktika, was built at Baltic Shipyard and remained in service from 1975 to 2008. She became the first surface vessel to reach the North Pole. The icebreaker was briefly renamed after General Secretary Leonid Brezhnev in 1982, but got her original name back in 1986.
The subsequent Arktika-class vessels had a special polymer coating applied to their hulls to reduce friction. They could break ice by moving forward as well as backward, making it virtually impossible for them to get caught in an ice trap.
Since these vessels were originally designed to operate in the cold Arctic waters, they cannot traverse to the Antarctic: in the course of such a voyage, the temperature in some of their compartments would rise to 50 degrees Celsius even at low reactor power settings.
The Arktika-class icebreakers can operate independently for up to eight months. During the 1999-2000 season, the very first such vessel set a record of independent operation by spending the entire year at sea without a single malfunction.
In August 2005, the Arktika set another record by clocking its millionth nautical mile since entry into service, thus covering nearly five times the distance between the Earth and the Moon.
The Arktika-class icebreakers are currently used both in support of merchant operations and to deliver relief crews to drifting Arctic science stations. Since 1990, they have also been carrying tourists on cruises towards the North Pole.
Each of the vessels features a comfortable section of tourist compartments, swimming pool, 100-seat cinema, gym, library, and even a sauna.
The subsequent Arktika-class vessels — the Sibir (commissioned in 1977, decommissioned in 1992), Rossiya (1985-2013), and Sovetsky Soyuz (1989-2010) – expedited the exploration of the Arctic region.
A new milestone in the history of Arctic maritime transportation was reached with the 1988 commissioning of the icebreaking carrier Sevmorput. In a single trip she could carry enough food, clothing, and equipment to last Russia's Far Northern residents the whole year.
Early this year, it was announced that the Sevmorput, which had long been moored, would shortly resume operation. She is primarily required by the Russian Defense Ministry to support the deployment and presence of military units in the Arctic, help restore the airfield and sea port infrastructure on the New Siberian Islands, Franz Joseph Land, and other Arctic territories.
Another unique Russian nuclear-powered icebreaker type is represented by the shallow-draft Taimyr (1988) and Vaygach (1990) projects, built at Helsinki New Shipyard with Soviet high-strength steel and outfitted with Soviet-designed equipment, including the reactors. These vessels are intended for use in the shallow estuary waters of such Arctic rivers as the Ob and the Yenisey.
After the USSR's collapse, despite all the financial hardships encountered by the country, Russia's nuclear-powered icebreaker fleet continued to evolve. The Yamal (1992) and the 50 Let Pobedy (2007, the world's most powerful icebreaker), both built under the Arktika project, remain in operation.
Both these vessels are stationed in Murmansk, which is home to the Russian icebreaker fleet's managing company Atomflot.
Russian engineers continue to work on new designs, and have recently laid the keel for the first vessel of the new LK-60Ya project icebreaker at the Baltic Shipyard. This variable-draft icebreaker will be capable of replacing two current types at once – the Arktika and the Taimyr. The LK-60Ya construction project costs around $1.113 billion, and two more such vessels are going to be built.
Russia is also developing the LK-110Ya nuclear icebreaker, which will be capable of ensuring year-round navigability of the Northern Sea Route and of supporting Arctic expeditions. The design is expected to be finalized by 2016.


The No. 1 reason its customers have been defaulting on mortgage loans is because their income was cut. That accounted for almost 60 percent of its loan defaults in the first 10 months of this year; add in sickness and divorce and the total jumps to more than 80 percent.
80% of loans in default are due to changes in homeowners' financial situations.
The federal government has unveiled a loan modification program that will attempt to help homeowners facing higher loan payments, by asking lenders to freeze the interest rates at the current levels, for at least a couple years.
Some 1.2 million households could be affected by the plan, at least by the government's estimates. Analysts see the numbers coming in much lower at around 350,000, given the strict eligibility requirements.
Finally, using past figures, a separate study done estimates that, in good times, the "re-default" rates for loans which had their rates reset to lower levels reaches 25% for conventional loans and between 40-60% for "Alt-A" and "subprime" loans. In good times.
Meaning, it looks as though 50% of those who can take advantage of lower rates offered through the government's plan may end up defaulting, regardless.


A quick share for today – a video from the National Theatre in the UK about playing Greek Chorus. Produced to tie in with their recent production of Medea starring Helen McCrory in the lead role, the video explores the portrayal and interpretation of the collective voice in modern productions – always a challenge for directors and actors.
Another interesting video, connected with the same production, is an interview with McCrory about her preparation for the role.
The idea of a national theatre, one that celebrates its country's cultural and performance heritage is a known around the world. A quick look at this list confirms that fact. The Comédie-Française in Paris, which was founded in 1680, is thought to be the world's first national theatre, but it is clear that a theatre supported by the state is considered by most countries to be an integral part of its cultural fabric.
This month, the National Theatre in the UK celebrates its 50th year and there are a whole host of events connected with the anniversary. I will be sharing many of them here as they will have a relevance and a resonance for any theatre student, no matter where you find yourself reading this. The National, as it is known, plays a huge role in defining the production of quality theatre in the UK, and although not alone in this by any means, it's very prominent London base, on the river Thames, means it is known around the world. For me personally The National is at the very heart of my involvement with theatre. I remember my first visit at the age of 16 and being in awe of the brutalist building and what it represented. I may not have lived in the UK for many years, but whenever I visit London, I go. I can't recall ever seeing a poor production and without a doubt some of the best theatre I have ever seen has been at The National. For 30 of its 50 years I have been a patron and I always will be.
What fascinates me, however, is that the land that gave the world William Shakespeare didn't have its own national theatre until 1963 and even then, it didn't have a permanent home until 1976. You can read a short history here, from the BBC, The bumpy road to the National Theatre.
Alternatively you can listen to a radio programme from BBC Radio 4, The Road to the National Theatre, (this is the first of two parts) that explores the same journey. In it the journalist James Naughtie sets out to discover why founding it took so long and what was learned along the way. Click to play, below. Fascinating!
In the last decade, The National has forged an international reputation with shows such as The History Boys and even more successfully, War Horse, both of which have toured internationally.
For a theatre student, the next month or so promises lots of great resources that can be shared, and I will start that with my next post. However, to round this one off, two things that I found interesting were, firstly, the US does not have a state funded national theatre. Secondly, War Horse is about to open in Berlin, in translation – the first time for a play originating from The National. This is particularly noteworthy because it is the first time the first World War has been discussed on a German stage. This article from The Telegraph, written by Dominic Cavendish, discusses the implications of this staging – War Horse in Berlin: behind the scenes – both for The National and German audiences.


Our fieldwork in Cambodia, Chile, Israel, Palestine, Tunisia and South Africa has now been completed.
We want to take this opportunity to thank each of our local consultants for their commitment, hard work and dedication in preparing background papers, opening doors and co-ordinating interviews. It has been a genuine pleasure to work with such sincere and impressive individuals.