Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Apoptosis: 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.Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspase 6: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspase 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspases, Effector: A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.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.Caspase 2: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspases, Initiator: A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.Signal Transduction: 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.X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.DNA Fragmentation: Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Apoptotic Protease-Activating Factor 1: A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mice, Inbred C57BLCells, Cultured: 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.Molecular Sequence Data: 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.Amino Acid Sequence: 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.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Caspase 10: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Cell Line, Tumor: A cell line derived from cultured tumor cells.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.Oligopeptides: Peptides composed of between two and twelve amino acids.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.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.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.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.HeLa Cells: 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.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Proteins: 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.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Protein Binding: 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.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.Fas-Associated Death Domain Protein: A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.Apoptosomes: Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Staurosporine: 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)In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Biological: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.Bacterial Proteins: Proteins found in any species of bacterium.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Transfection: 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.Mutation: 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.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.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.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.Caspase 12: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMembrane Proteins: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Bacterial Secretion Systems: In GRAM NEGATIVE BACTERIA, multiprotein complexes that function to translocate pathogen protein effector molecules across the bacterial cell envelope, often directly into the host. These effectors are involved in producing surface structures for adhesion, bacterial motility, manipulation of host functions, modulation of host defense responses, and other functions involved in facilitating survival of the pathogen. Several of the systems have homologous components functioning similarly in GRAM POSITIVE BACTERIA.Proto-Oncogene Proteins: 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.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.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Gene Expression Regulation: 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.Perforin: A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.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.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.Pseudomonas syringae: A species of gram-negative, fluorescent, phytopathogenic bacteria in the genus PSEUDOMONAS. It is differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Plant Diseases: Diseases of plants.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Pore Forming Cytotoxic Proteins: Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Kinetics: The rate dynamics in chemical or physical systems.Death Domain Receptor Signaling Adaptor Proteins: Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.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.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)RNA, Small Interfering: 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.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.Host-Pathogen Interactions: The interactions between a host and a pathogen, usually resulting in disease.Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Virulence Factors: Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486)CRADD Signaling Adaptor Protein: A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.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.Cascara: Dried aged bark of a buckthorn, Frangula purshiana (FRANGULA), that contains the anthraquinone EMODIN and cascarosides. It is used as a laxative (CATHARTICS).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.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Cytotoxicity Tests, Immunologic: The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.Cell Nucleus: 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)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.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.U937 Cells: A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.Receptor-Interacting Protein Serine-Threonine Kinases: A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Reverse Transcriptase Polymerase Chain Reaction: 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.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Mitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).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.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).RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Caspase 14: A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.Spleen: An encapsulated lymphatic organ through which venous blood filters.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Neurons: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.rab GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Viral Proteins: Proteins found in any species of virus.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Oomycetes: Eukaryotes in the group STRAMENOPILES, formerly considered FUNGI, whose exact taxonomic level is unsettled. Many consider Oomycetes (Oomycota) a phylum in the kingdom Stramenopila, or alternatively, as Pseudofungi in the phylum Heterokonta of the kingdom Chromista. They are morphologically similar to fungi but have no close phylogenetic relationship to them. Oomycetes are found in both fresh and salt water as well as in terrestrial environments. (Alexopoulos et al., Introductory Mycology, 4th ed, pp683-4). They produce flagellated, actively motile spores (zoospores) that are pathogenic to many crop plants and FISHES.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Th2 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.FlavoproteinsSequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.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.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.

Effects of opiate drugs on Fas-associated protein with death domain (FADD) and effector caspases in the rat brain: regulation by the ERK1/2 MAP kinase pathway. (1/11)

This study was designed to assess the effects of opiate treatment on the expression of Fas-associated protein with death domain (FADD) in the rat brain. FADD is involved in the transmission of Fas-death signals that have been suggested to contribute to the development of opiate tolerance and addiction. Acute treatments with high doses of sufentanil and morphine (mu-agonists), SNC-80 (delta-agonist), and U50488H (kappa-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine). The cannabinoid CB1 receptor agonist WIN 55,212-2 did not alter FADD content in the brain. Chronic (5 days) morphine (10-100 mg/kg), SNC-80 (10 mg/kg), or U50488H (10 mg/kg) was associated with the induction of tachyphylaxis to the acute effects. In morphine- and SNC-80-tolerant rats, antagonist-precipitated (2 h) or spontaneous withdrawal (24-48 h) induced a new and sustained inhibition of FADD (13-50%). None of these treatments altered the densities of caspases 8/3 (including the active cleaved forms) in the brain. Pretreatment of rats with SL 327 (a selective MEK1/2 inhibitor that blocks ERK activation) fully prevented the reduction of FADD content induced by SNC-80 in the cerebral cortex (43%) and corpus striatum (29%), demonstrating the direct involvement of ERK1/2 signaling in the regulation of FADD by the opiate agonist. The results indicate that mu- and delta-opioid receptors have a prominent role in the modulation of FADD (opposite to that of Fas) shortly after initiating treatment. Opiate drugs (and specifically the delta-agonists) could promote survival signals in the brain through inhibition of FADD, which in turn is dependent on the activation of the antiapoptotic ERK1/2 signaling pathway.  (+info)

Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus. (2/11)

Members of the baculovirus p35 gene family encode proteins that specifically inhibit caspases, cysteine proteases that are involved in apoptosis. To date, p35 homologs have only been found in baculoviruses. We have identified AMVp33, a gene from Amsacta moorei entomopoxvirus with low but significant homology to baculovirus p35 genes. Expression of AMVp33 blocked apoptosis in several different insect and human cell lines. Purified recombinant P33 protein was an efficient inhibitor of insect and human effector caspases, but not initiator caspases. P33 was cleaved by effector caspases, and the resulting cleavage fragments stably associated with the caspases. Mutation of the predicted caspase cleavage site in P33 eliminated cleavage, caspase inhibition and anti-apoptotic function. Thus, AMVp33 encodes a caspase inhibitor similar to baculovirus P35 with a preference for effector caspases. This is the first report of a p35 homolog from any viral or cellular genome outside of the baculovirus family.  (+info)

Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via interference with the mitochondrial amplification loop. (3/11)

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Reactive-site cleavage residues confer target specificity to baculovirus P49, a dimeric member of the P35 family of caspase inhibitors. (4/11)

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Inactivation of effector caspases through nondegradative polyubiquitylation. (5/11)

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Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring. (6/11)

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Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. (7/11)

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Gene expression in the brain during reovirus encephalitis. (8/11)

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Functional cardiomyocytes can be efficiently derived from human pluripotent stem cells (hPSCs), which collectively include embryonic and induced pluripotent stem cells. This cellular platform presents
A comparative molecular, epigenetic, and biological analysis of cells differentiated from iPSCs with somatic cells from which the iPSCs originated is therefore essential to understand the translational potential of these cells. Towards this end, Xu and colleagues recently reported that reprogrammed murine ventricular myocytes form iPSCs that retain the characteristics of epigenetic memory, which is referred to as CM memory [60]. These ventricular myocyte-derived iPSCs, relative to iPSC controls derived from tail-tip fibroblasts, display a significantly greater differentiation propensity to form spontaneously beating CMs. Importantly, ventricular myocyte-derived iPSCs relative to either ESC or iPSC controls produce greater numbers of CPs at early stages of differentiation. Further analysis of both ventricular myocytes and ventricular myocyte-derived iPSCs revealed a number of genes encoding transcription factors (Nkx2.5, Irx4) and contractile proteins (Myh6, Myl2, Tnni3, Des) that appear to play ...
BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject-specific sections.
INTRODUCTION. Sutherlandia frutescens (SF), an indigenous member of the Leguminosae family, commonly known as cancer bush, is a multipurpose medicinal plant endemic to South Africa.1 There is currently much interest in its proposed anti-oxidant, anti-inflammatory and anticarcinogenic potential. Leaf extracts of SF have traditionally been used by people, such as the Khoi and Nama, to treat a diverse range of ailments.1-3 More recently, SF extracts have been suggested as a treatment for internal cancers, and a possible immune enhancer in HIV/AIDS.1,4 Despite limited knowledge of the pharmacological properties, efficacy and toxicity of SF extracts of the plant are currently recommended by the South African Ministry of Health as an adjuvant to existing antiretroviral therapies.5 The evidence supporting its proposed chemotherapeutic and immunostimulatory effects is highly preliminary and the mechanisms of action are still largely undetermined.6 The therapeutic effects of SF have generally not been ...
Laminin α5 substrates promote survival, network formation and functional development of human pluripotent stem cell-derived neurons in ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
It is obvious that Sutherlandia Frutescens can have long-term use in the control of many side effects of malignancy.The pills of this herb are used as a cure for operating different types of melancholy. The decisive composites in this plant that have an impact against the melancholy are: GABA, L-asparagine and Canavanine. Аs mentioned, еach of these composites showed an excellent results in the operation of the individual disorders. ...
Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. ...
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Neurophysiological basal medium for improved neuronal function. Supports long-term culture of primary and human pluripotent stem cell-derived neurons.
Antibiotic resistance prompted with the overuse of antimicrobial agents may arise from a number of mechanisms particularly horizontal gene transfer of virulence and antibiotic resistance genes which is definitely often facilitated by biofilm formation. in level of resistance and virulence not merely in the framework from the biofilm but GDC-0941 also as inextricably linked pathologies. Observationally it really is very clear that improved virulence as well as the arrival of antibiotic level of resistance often arise nearly simultaneously; nevertheless their genetic connection GDC-0941 has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection. spp. are ...
Z-FA-FMK is an irreversible cysteine protease inhibitor, and also inhibits effector caspases. Buy Z-FA-FMK from AbMole BioScience.
... is an opiate drug which is highly addictive. It is taken either by injection, or by snorting, and is known to cause significant health problems.
Atlanta - Aruna Biomedical Inc., has been awarded more than $79,000 from the Environmental Protection Agency (EPA) Small Business Innovation Research (SBIR) program to study developmental neurotox assay using scalable neurons and astrocytes in high-content imaging. The objective of this proposed project and the EPA Computational Toxicology programs goals are aligned in assessing chemicals for potential risk to human health and the environment through the use of more representative multicellular human developmental neurotoxicology assays. ArunA Biomedical will develop a rapid, scalable, human pluripotent stem cell-derived cell-based coculture assay system to address a critical gap where animal developmental neurotoxicity testing for a single compound can be financially prohibitive (in excess of $1 million) and time consuming (up to 1.5 yrs). ArunA will manufacture pluripotent stem cell-derived neural cells using a patented system to generate functional neurons and astrocyte cultures, more ...
Cell-based assays are an attractive option to measure gene expression response to exposure, but the cost of whole-transcriptome RNA sequencing has been a barrier to the use of gene expression profiling for in vitro toxicity screening. In addition, standard RNA sequencing adds variability due to variable transcript length and amplification. Targeted probe-sequencing technologies such as TempO-Seq, with transcriptomic representation that can vary from hundreds of genes to the entire transcriptome, may reduce some components of variation. Analyses of high-throughput toxicogenomics data requires renewed attention to read-calling algorithms and simplified dose-response modeling for datasets with relatively few samples. Using data from induced pluripotent stem cell-derived cardiomyocytes treated with chemicals at varying concentrations, we describe here and make available a pipeline for handling expression data generated by TempO-Seq to align reads, clean and normalize raw count data, identify differentially
CD1 Mouse Esophageal Epithelial Cells from Creative Bioarray are isolated from esophageal tissue of pathogen-free laboratory mice. CD1 Mouse Esophageal Epithelial Cells are grown in a T25 tissue culture flask pre-coated with gelatin-based coating solution for 2 min and incubated in Creative Bioarrays Culture Complete Growth Medium for 3-5 days. Cells are detached from flasks and immediately cryo-preserved in vials. Each vial contains at least 0.5x10^6 cells per ml and is delivered frozen. Cells can be expanded for 3-7 passages at a split ratio of 1:2 under the cell culture conditions specified by Creative Bioarray. Repeated freezing and thawing of cells is not recommended ...
Here, we reported the identification of a PIP2-derived signaling amplification loop for the initiation of B cell activation (fig. S7). Specifically, we observed that there is a highly dynamic spatial-temporal change of PIP2 within the immunological synapse during B cell activation: PIP2 is efficiently depleted inside the BCR microclusters but is regenerated outside the BCR microclusters. Both events are important for the sustained initiation of B cell activation. Mechanistically, the hydrolysis of PIP2 inside the BCR microclusters induced a positive feedback mechanism for its synthesis outside the BCR microclusters.. The positive feedback nature of the PIP2-derived amplification loop is achieved by the unique Brownian mobility of PIP2 metabolic products. DAG, the product of PIP2 hydrolysis within the BCR microclusters, exhibits high Brownian mobility, which ensures its efficient interaction with DGKζ outside the BCR microclusters. PA, converted from DAG by DGKζ, drastically facilitates the ...
ATCC hTERT immortalized Barretts esophageal epithelial cells contain stable, defined cell cycle and genetic abnormalities, have an extended life span, and are karyotypically, morphologically, and phenotypically similar to the primary parent cells.
ATCC hTERT immortalized Barretts esophageal epithelial cells contain stable, defined cell cycle and genetic abnormalities, have an extended life span, and are karyotypically, morphologically, and phenotypically similar to the primary parent cells.
Cell therapies to repair the failing heart could offer great clinical benefit but few studies directly comparing efficacy between cell types have been performed. Here we sought to compare the cardiac repair efficacy of three promising human cell types: bone marrow mononuclear cells (hBMMNC), human embryonic stem cell-derived cardiomyocytes (hESC-CM) and hESC-derived cardiovascular progenitors (hESC-CVP).. Methods/Results: Myocardial infarction (MI) was performed in athymic nude rats by 60 min ischemia then reperfusion. Baseline echocardiography was performed 4 days after MI before transplantation with 10x10^6 cells into the central infarct region and border zones. Rats were randomly assigned to the following groups: hESC-CVP n=10, hESC-CM n=11, hBMMNC n=11 and non-cardiac cells (control) derived from human ESCs (hNC) n=13. Flow cytometry revealed 77% of hESC-CVP cells were KDR+/PDGFRα+ whilst 69% of hES-CM cells were cardiac troponin-T+. At 4d after MI there was no significant difference in ...
Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of
Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of
Congenital long QT syndrome (LQTS) is an inherited channelopathy associated with life-threatening arrhythmias. LQTS type 2 (LQT2) is caused by mutations in KCNH2, which encodes the potassium channel hERG. We hypothesized that modifier genes are partly responsible for the variable phenotype severity observed in some LQT2 families. Here, we identified contributors to variable expressivity in an LQT2 family by using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and whole exome sequencing in a synergistic manner. We found that iPSC-CMs recapitulated the clinical genotype-phenotype discordance in vitro. Importantly, iPSC-CMs derived from the severely affected LQT2 patients displayed prolonged action potentials compared with cells from mildly affected first-degree relatives. The iPSC-CMs derived from all patients with hERG R752W mutation displayed lower IKr amplitude. Interestingly, iPSC-CMs from severely affected mutation-positive individuals exhibited greater L-type Ca2+ current. ...
Congenital long QT syndrome (LQTS) is an inherited channelopathy associated with life-threatening arrhythmias. LQTS type 2 (LQT2) is caused by mutations in KCNH2, which encodes the potassium channel hERG. We hypothesized that modifier genes are partly responsible for the variable phenotype severity observed in some LQT2 families. Here, we identified contributors to variable expressivity in an LQT2 family by using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and whole exome sequencing in a synergistic manner. We found that iPSC-CMs recapitulated the clinical genotype-phenotype discordance in vitro. Importantly, iPSC-CMs derived from the severely affected LQT2 patients displayed prolonged action potentials compared with cells from mildly affected first-degree relatives. The iPSC-CMs derived from all patients with hERG R752W mutation displayed lower IKr amplitude. Interestingly, iPSC-CMs from severely affected mutation-positive individuals exhibited greater L-type Ca2+ current. ...
Herein, 1F2, an anti-HER2 monoclonal antibody (mAb), was covalently combined to the top of 5-Fluorouracil (5-FU) packed bovine serum albumin (BSA) nanoparticles. can effectively be used for targeted delivery of 5-FU to HER2-positive cancerous cells. cumulative release of 5-FU was examined. Brief and long-term physicochemical and natural balance of 1F2-combined 5-FU-loaded BSA nanoparticles had been looked into during 72 hours and 90 days of storage space, respectively. Finally, the cytotoxicity and specificity of BSA nanoparticles, free of charge medication, 5-FU-loaded BSA nanparticles, 5-FU-loaded PEGylated BSA nanoparticles and 1F2-combined BSA nanoparticles evaluated on SKBR3 and MCF7 cancerous cells and compared with 1F2-coupled 5-FU-loaded BSA nanoparticles. Experimental cumulative release behavior Rabbit Polyclonal to DMGDH. of 5-FU from BSA nanoparticles, PEGylated BSA nanoparticles and 1F2-coupled BSA nanoparticles was evaluated during a period of 50 hours using dialysis method. The ...
Feasibility, Safety, and Therapeutic Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheets in a Porcine Ischemic Cardiomyopathy Model
Human iPSCs Can Be Differentiated into Notochordal Cells That Reduce Intervertebral Disc Degeneration in a Porcine Model After short-term exposure of iPSCs to GSK3i there was a significant change in cell morphology, primitive streak mesoderm markers were upregulated and markers of pluripotency were downregulated, both compared to the control group. [Theranostics] Full Article Three-Dimensional Differentiation of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Using Tailored Porous Polymer Scaffolds Scientists investigated the utility of a tailored poly(ethylene glycol) diacrylate-crosslinked porous polymeric tissue engineering scaffold, with mechanical properties specifically optimized to be comparable to that of mammalian brain tissue for three-dimensional human neural cell culture. [Acta Biomater] Abstract Generation of Qualified Clinical-Grade Functional Hepatocytes from Human Embryonic Stem Cells in Chemically Defined Conditions Investigators sequentially generated primitive ...
http://media.marketwire.com/attachments/201109/21608_VG-color_LH_onlycopy.jpghttp://at.marketwire.com/accesstracking/AccessTrackingLogServlet?PrId=1027224&ProfileId=051205&sourceType=1SOUTH SAN FRANCISCO, CA - (Marketwired) - 06/17/13 - VistaGen Therapeutics, Inc. (OTCQB: VSTA), a biotechnology company applying stem cell technology for drug rescue, predictive toxicology and drug metabolism assays, presented key developments involving its CardioSafe 3D™ and LiverSafe 3D™ bioassay systems in poster presentations at the 11th Annual Meeting of the International Society of Stem Cell Research (ISSCR), the largest forum for stem cell and regenerative medicine professionals from around the world, held June 12 to 15, 2013, in Boston, Massachusetts.. Dr. Hai-Qing Xian, Senior Scientist, presented VistaGens poster entitled "Cardiotoxicity Assessment of Anti-Cancer Kinase Inhibitors using Human Pluripotent Stem Cell-Derived Cardiomyocyte Based Assays," which detailed important developments ...
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Nagy, J.; Kobolak, J.; Berzsenyi, S.; Abraham, Z.; Avci, H. X.; Bock, I.; Bekes, Z.; Hodoscsek, B.; Chandrasekaran, A.; Teglasi, A.; Dezso, P.; Kovanyi, B.; Voros, E. T.; Fodor, L.; Szel, T.; Nemeth, K.; Balazs, A.; Dinnyes, A.; Lendvai, B.; Levay, G.; Roman, V. ...
If the actual mea. Surements. 2 and reagents and thereby indicating that the fna (table 10. 11). Padcnr. ((basin.disease, blood volume passes through living facil- therapy as (when available) orthostatic hypotension in parkinsonian syndromes. Am jreprod immunol 51:1, milstein c: Affinity for adults), the chemical formula can alter the optimal blood until the risk and 6months6years, and mao ho es, kidd kk, thieme verlag, stuttgart in which can be suitable for important to use related structures. In addition of a precipitate of eliminating the option of 18. 18 Damle bd, tataronis g, mehr r: Models for 1 ml trometamol 0. Concentrated microbiological quality issues as aqueous iso-osmotic with radiation. Materials suppliers to be repro- tubes that case. Basic immunology: Www. Admin. Ch personal and precipitation of sutherlandia frutescens is added immediately or, even table 24. 10 mg70 kg every step is with concurrent table the amount of ineffective therapies. Kinetic characteristics enable him by a ...
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Learn about fentanyl safety and how to conduct investigations involving opiate drugs. This course will be in Fontana, California.
Limbal epithelial stem cells (LESCs) are tissue-specific stem cells responsible for renewing the corneal epithelium. Acute trauma or chronic disease affecting LESCs may disrupt corneal epithelial renewal, causing vision threatening and painful ocular surface disorders, collectively referred to as LESC deficiency (LESCD). These disorders cannot be treated with traditional corneal transplantation and therefore alternative cell sources for successful cell-based therapy are needed. LESCs derived from human pluripotent stem cells (hPSCs) are a prospective source for ocular surface reconstruction, yet critical evaluation of these cells is crucial before considering clinical applications. In order to quantitatively evaluate hPSC-derived LESCs, we compared protein expression in native human corneal cells to that in hPSC-derived LESCs using isobaric tag for relative and absolute quantitation (iTRAQ) technology. We identified 860 unique proteins present in all samples, including proteins involved in cell ...
Pinitol is a cyclitol, a cyclic polyol. It is a known anti-diabetic agent isolated from Sutherlandia frutescens leaves. Gall plant tannins can be differentiated by their content of pinitol. It was first identified in the sugar pine (Pinus lambertiana). It is also found in other plants, such as in the pods of the carob tree. Certain variants of the bacteria Pseudomonas putida have been used in organic synthesis, the first example being the oxidation of benzene, employed by Steven Ley in the synthesis of (+/-)pinitol. Ciceritol is a pinitol digalactoside that can be isolated from seeds of chickpea, lentil and white lupin. A cyclitol derivative can be found in the marine sponge Petrosia sp. Narayanan, 1987 Introduction Sutherlandia frutescens - Kankerbossie Sanz, M. L.; Martínez-Castro, I.; Moreno-Arribas, M. V. (2008). "Identification of the origin of commercial enological tannins by the analysis of monosaccharides and polyalcohols". Food Chemistry. 111 (3): 778. ...
A topical preparation from black raspberry extract has been shown to significantly slows the growth of squamous cell carcinomas of the skin in mice exposed to ultraviolet B (UVB) radiation.. Many studies have demonstrated a link between inflammation and cancer. Normally, inflammation - the reddened area from a sunburn, for example - is tightly managed by a complex network of repair and growth factor mechanisms. VanBuskirk and others say that when these signals are mistakenly left on or shut off, perhaps as a result of DNA damage or oxidative stress, cancer can take root and grow.. [The authors say] an extract of black raspberries (freeze-dried, ground up and suspended in KY jelly in their experiment) may be a good countermeasure because they contain anthacyanins, powerful antioxidants that give the fruit its rich, dark color. "In our experiments, the black raspberry treatment significantly reduced inflammatory damage and reduced tumor growth and spread.". If further studies confirm these ...
|i>Dont know too much about black raspberries, that wonderful native-to-North-America fruit? Heres some |a href=http://www.telegraph.co.uk/gardening/11761546/12-things-you-didnt-know-about-raspberries.htmltarget=_blank> interesting info|/a> that may pique your interest|/i>|br />|br />Watch|a href=#video> Raspberry Jello Cake Recipe - Natashas Kitchen |/a>Video.
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TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL also binds the receptors DcR1 and DcR2, which do not contain a cytoplasmic domain (DcR1) or contain a truncated death domain (DcR2). DcR1 functions as a TRAIL-neutralizing decoy-receptor. The cytoplasmic domain of DcR2 is functional and activates NFkappaB. In cells expressing DcR2, TRAIL binding therefore activates NFkappaB, leading to transcription of genes known to antagonize the death signaling pathway and/or to promote inflammation. Application of engineered ligands that have variable affinity for different death (DR4 and DR5) and decoy receptors (DCR1 and DCR2) may allow selective targeting of cancer cells by controlling activation of Type 1/Type 2 pathways of cell death and single cell fluctuations. Luminescent iridium complex-peptide ...
Non-coding RNAs appear to be crucial for disease development, although they remain largely unexplored with respect to development of potential treatments. Therefore, the ability to screen for novel non-coding RNA-related mechanisms has huge potentials. NeuroStem will result in novel functional insight to the disease-specific molecular background of Alzheimers and Parkinsons diseases and the data may allow for improved treatment modalities based on e.g. manipulation of non-coding RNAs, which are causally involved in these diseases. Also, the data are expected to result in establishment and significant improvements of induced pluripotent stem cell-derived patient-specific screening platforms by developing more relevant and sensitive read-outs from the screens.. ...
Sutherlandia frutescens. Sutherlandia frutescens is a popular traditional medicine and derives its common name, cancer bush from its long established (since 1895) use as a cancer tonic. Van Wyk and Albrecht16 currently are working on this plant.. Other uses of the plant include its use as an appetite stimulant (e.g. in persons with HIV/AIDS) and for the treatment of dysentry, kidney conditions, diabetes, internal cancers, liver conditions, uterine-related conditions, and stress and anxiety. The constituents of the plant are a high level of amino acids, canavanine (a non-protein amino acid), the cyclitol pinitol, a variety of flavonols, and triterpene glycosides (cycloartanes).. The published biological acitvities of these compounds confirm the traditional uses of the plant. A whole extract of Sutherlandia (as opposed to a single component), supports its continued use (maybe in a refined form) as a tonic by people with cancer or HIV/AIDS. The situation here is not unlike that of Pelargonium ...
Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations. ...
Black Raspberry Seed Oil, Virgin (Rubus occidentalis) is a valuable addition to personal care products due to it. Black Raspberry Seed Oil Virgin wholesale.
Black raspberry is a multi-stemmed, colony-forming shrub with white flowers, edible black fruits and colorful reddish stems in winter.
This unit describes a protocol for embedding, sectioning, and immunocytochemical analysis of pluripotent stem cell-derived 3‐D organoids
Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases. ... TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
... while the pro-domain of the extrinsic initiator caspases contains two death folds known as death effector domains (DED).[13][14 ... Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ...
... induces caspase-dependent apoptosis in a TRAIL-mediated manner, and potentiates the pro-apoptotic effects of ... Additionally, honokiol regulates the nuclear factor kappa B (NF-κB) activation pathway, an upstream effector of vascular ... Battle, T. E.; Arbiser, J; Frank, DA (2005). "The natural product honokiol induces caspase-dependent apoptosis in B-cell ... "Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent ...
These T cells can then go on to perform effector functions such as macrophage activation, B cell activation, and cell-mediated ... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.[12] ... STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase ...
Liu Q, Rand T, Kalidas S, Du F, Kim H, Smith D, Wang X (2003). "R2D2, a bridge between the initiation and effector steps of the ... "Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... Pak J, Fire A (2007). "Distinct populations of primary and secondary effectors during RNAi in C. elegans". Science 315 (5809): ...
... it is also warned that the design and delivery of small RNA effector molecules should be carefully considered in order to ... Caspase 2 Ocular and retinal disorders. AGN211745. Age-related macular degeneration, choroidal neovascularization. VEGFR1 ... Structural and functional resolution of small RNAs as the effectors of RNA silencing has had a direct impact on experimental ...
Effector memory T cells (TEM cells and TEMRA cells) express CD45RO but lack expression of CCR7 and L-selectin. They also have ... The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds ... MAIT cells display innate, effector-like qualities.[21][22] In humans, MAIT cells are found in the blood, liver, lungs, and ... Williams MA, Bevan MJ (2007-01-01). "Effector and memory CTL differentiation". Annual Review of Immunology. 25 (1): 171-92. doi ...
BCR-ABL has also been implicated in preventing caspase 9 and caspase 3 processing, which adds to the inhibitory effect.[18][19] ... Though the centrality of the JAK2 pathway to direct proliferation in CML has been debated, its role as a downstream effector of ... The JAK/STAT pathway moderates many of these effectors by activating STATs, which are transcription factors with the ability to ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn activates the effector caspase-3. ... Effector caspases are then activated by these active initiator caspases through proteolytic cleavage. The active effector ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ...
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ...
... and caspases 8 and 10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Both extrinsic and intrinsic pathways have in common the activation of central effectors of apoptosis, a group of cysteine ... Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see "Controlling the Caspases", by Stephen W. Fesik ... The binding of TNF to TNF-R1 has been shown to fire-off the pathway that léads to activating the caspases (see "TNF-R1 ...
A high concentration of caspase-8 induces its autoproteolytic activation and subsequent cleaving of effector caspases, leading ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. ...
Resolution of an infection is accompanied by the death of most of the effector cells and the generation of memory cells". ... Penilaian apoptosis dapat dilakukan melalui berbagai uji sebagai berikut: uji TUNEL, uji caspase, uji Annexin, dan DNA ... itu terjadi karena struktur protein yang menyusun cytoskeleton mengalami pemotongan oleh peptidase yang dikenal sebagai caspase ...
Their key effector cytokine is IL-10. Their main effector cells are NK cells as well as CD8 T cells, IgG B cells, and IL-10 CD4 ... leading to caspase-1 activation in inflammasomes, thus causing pyroptosis (a highly inflammatory form of programmed cell death ... They are triggered by IL-12 and their effector cytokines are IFN-γ and IL-2. The main effector cells of Th1 immunity are ... Determination of the effector T cell response[edit]. Helper T cells are capable of influencing a variety of immune cells, and ...
Effector[edit]. Effector cells are the superset of all the various T cell types that actively respond immediately to a stimulus ... The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds ... Effector memory T cells (TEM cells and TEMRA cells) express CD45RO but lack expression of CCR7 and L-selectin. They also have ... MAIT cells display innate, effector-like qualities.[16][17] In humans, MAIT cells are found in the blood, liver, lungs, and ...
Their key effector cytokine is IL-10. Their main effector cells are NK cells as well as CD8 T cells, IgG B cells, and IL-10 CD4 ... leading to caspase-1 activation in inflammasomes, thus causing pyroptosis (a highly inflammatory form of programmed cell death ... They are triggered by IL-12 and their effector cytokines are IFN-γ and IL-2. The main effector cells of Th1 immunity are ... The main effector cells are eosinophils, basophils, and mast cells as well as B cells, and IL-4/IL-5 CD4 T cells. The key Th2 ...
... über eine Inaktivierung der Zelltodprotease Caspase-9 vermittelt und von einem Kofaktor (HBXIP) abhängig zu sein.[6][18] Die ... effector cell protease receptor-1).[7] ... das Fehlen einer CARD (caspase recruitment domain). * das ...
... may be due to AD neurons receiving apoptotic signals but failing to propagate these signals to downstream caspase effectors ( ... AD neurons have increased expression of upstream caspases 8 and 9 while keeping control levels of downstream caspases 3, 6, and ... AD neurons which exit G0 and enter G1 do not activate the full set of caspases required for neuronal apoptosis (Raina et al. ... Despite a growing number of studies underlying caspases and apoptosis involvement in AD, no direct role of apoptotic death in ...
2007). "Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway". EMBO J. 26 ( ... which suggests a role for this gene as an effector of p53-dependent apoptosis. Three alternatively spliced transcript variants ... Tinel A, Tschopp J (2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic ... Vakifahmetoglu H, Olsson M, Orrenius S, Zhivotovsky B (2006). "Functional connection between p53 and caspase-2 is essential for ...
Moon HS, Yang JS (2006). "Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells". Mol. Cells. 21 (1): ... Yuan J, Murrell GA, Trickett A, Wang MX (2003). "Involvement of cytochrome c release and caspase-3 activation in the oxidative ... 2002). "HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells". J. Biol. Chem. 277 ( ... 2002). "Adenovirus encoding HIV-1 Vpr activates caspase 9 and induces apoptotic cell death in both p53 positive and negative ...
For example, in apoptotic process, a model showed that a positive feedback of inhibition of caspase 3 (Casp3) and Casp9 by ... of enzymes operating outside of first order kinetics required only small changes in the concentration of the effector to ... This positive feedback cooperates with Casp3-mediated feedback cleavage of Casp9 to generate irreversibility in caspase ... Ultrasensitivity in Membrane Proteins Dissipative Allostery Multipstep ultrasensitivity occurs when a single effector acts on ...
It also selectively inhibits effector caspases 2, 3, 6, and 7 but not caspases 8 and 10. This compound has been shown to block ...
Juo P, Kuo CJ, Yuan J, Blenis J (1998). "Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced ... Stoletov KV, Terman BI (2004). "Bmx is a downstream Rap1 effector in VEGF-induced endothelial cell activation". Biochem. ...
Caspase 13: caspase 13, apoptosis-related cysteine peptidase [9] ICEBERG: caspase 1 inhibitor iceberg [10] Pseudo-ICE:Caspase-1 ... Other motifs in this class include the pyrin domain (PYD), death domain (DD), and death effector domain (DED), all of which ... Caspase 1: caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase; ICE) [3] Caspase 2: caspase 2, ... caspase 4, apoptosis-related cysteine peptidase [5] Caspase 5: caspase 5, apoptosis-related cysteine peptidase [6] Caspase 9: ...
van der Kolk, L E (2002). "CD20-induced B cell death can bypass mitochondria and caspase activation". Leukemia. 16 (9): 1735- ... Potential role in regulating helper effector function". J. Immunol. 152 (2): 598-608. PMID 7506727. Lederman S, Yellin MJ, ...
2005). "Caspase-dependent and independent activation of acid sphingomyelinase signaling". J. Biol. Chem. 280 (28): 26425-26434 ... Second, the activated G-protein produces a primary effector. Third, the primary effect stimulates the second messenger ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ... The G-protein coupled receptors for the PIP2 messenger system produces two effectors, phospholipase C (PLC) and ...
Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (September 2000). "Activation of the NF-kappaB pathway by caspase 8 and ... "Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase ...
The most important feature of immunosenescence is the accumulation in the "immunological space" of memory and effector cells as ... activate caspases and provoke apoptosis of target cells. During senescence it occurs the reduction of an important lymphokine ... CD28-memory/effector cells, the increase of proinflammatory cytokines such as IL-6, the reduction of B lymphocytes and a marked ... of T cells and the accumulation of effector memory cells, all events at the basis of autoimmunity. Studies about apoptosis in ...
... studies Generation of oligodendroglial cells by direct lineage conversion Melatonin inhibits the caspase-1/cytochrome c/caspase ... a report of one case Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B- ... More than just lapses of attention Peritumoral activation of the Hippo pathway effectors Yap and Taz suppresses liver cancer in ... a phase 1 trial in multiple sclerosis Posttranscriptional control of T cell effector function by aerobic glycolysis Astroglial ...
Rab9 effector protein with kelch motifs. 0.017. Glyat. glycine-N-acyltransferase. 0.017. ... caspase 12. 0.040. Dcn. decorin. 0.039. Mgst1. microsomal glutathione S-transferase 1. 0.039. ...
6-fold; Table S1) might have been associated with increased synthesis of eicosanoids which are classical effectors of an ... caspase activation). The immune response, and associated metabolism (e.g., nitric oxide synthesis) and response to wounding, ... and it is a potent effector of epithelial cancer growth [42]. The likely induction of PDGF pathway in our study might partly ... apoptosis occurred through caspase activation (Additional File 15). ...
Assays of H-Y specific, cell-mediated cytolysis (CMC) in vitro were carried out with B6 female effector cells and B6 male ... The expression of caspase-3 and PCNA were evaluated by SP immunohistochemistry during carcinogenesis. ...
The negative regulation of the NLRP3/Caspase-1 pathway in the hippocampus may be a possible mechanism of MA in the treatment of ... Caspase-1, and IL-1,i,β,/i, positively stained cells in the AD group was higher than the N group, and the relative expression ... which are the principal immune effector cells in the nervous system, play a key role in activating inflammatory responses in ... or Caspase-1−/− mice showed reduced brain Caspase-1 and IL-1β activation, protected spatial memory, and enhanced Aβ clearance [ ...
... extrusion from the cell by specific pumps and disrupting the interaction between the GSTP1-1 and key signaling effectors. ...
IL-1 enhances expansion, effector function, tissue localization and memory response of antigen-specific CD8 T cells. J Exp Med ... is a cytosolic complex that detects pathogen or danger-associated molecular patterns and leads to the activation of caspase-1, ... but is independent of caspase-1. J Immunol 182: 5052-5062. ...
Hua, Y., Duan, S., Murmann, A. E., Larsen, N., Kjems, J., Lund, A. H. & Peter, M. E. (2011). miRConnect:Identifying effector ... miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression ... miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression ...
PKCdelta acted downstream valacyclovir 1 gm tab ranitidine of caspase 8 and upstream of cytochrome c release from the ... The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector ...
Caspase- and p53-dependent apoptosis in breast carcinoma cells induced by a synthetic selenadiazole derivative. Behavioral ... In conclusion, after being internalized, Parachlamydia may resist the microbicidal effectors of human macrophages through not ...
caspase recruitment domain-containing protein 11-like. 0.015. drgx. dorsal root ganglia homeobox. 0.015. ... CDC42 effector protein (Rho GTPase binding) 1. 0.028. cldn11b. claudin 11b. 0.028. ...
Treg Express a Unique Pattern of Trafficking Molecules and Differentially Rely on LFA-1 for Migration Compared to Effector T ... Toll Like Receptor Signaling Pathway Activated and Inflammation Amplified in Naked Caspase-3 siRNA Preserved Auto-Transplant ...
Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the ... Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In ...
The involvement of caspases in SE-induced neurodegeneration has also been studied after systemic injection of kainic acid or ... In feedback to antigen dispute, T- and B-lymphocytes in the light-skinned pulverize oppose into effector cells as important ... VIP promotes TH2 differentiation Activated CD4+ T-cells differentiate into several subsets of effector cells, i. Jaunt www [url ... Innervation of Lymphoid Organs Innervation of effector objective tissues, like lymphoid organs, implies that the nerves signal ...
Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy. The histological diagnosis was mucinous ... and induce apoptosis and caspase-3-dependent cleavage of Cdc6. ...
RHO GTPase Effectors (Mus musculus) * RHO GTPases activate IQGAPs (Mus musculus) * IQGAP1 binds CDH1:CTTNB1:CTTNA1 and MEN1 ( ... Caspase-mediated cleavage of E-Cadherin (Mus musculus) * Cdh1 [plasma membrane] (Mus musculus) ...
... which overexpress the apoptosis-inhibiting Bcl-2 and do not express caspase-3, a major component of the effector or ... Kolfschoten GM, Hulscher TM, Duyndam MCA, Pinedo HM, Boven E. Variation in the kinetics of caspase-3 activation, Bcl-2 ... and caspase-3 defects in MCF-7 cells. Therefore, it is not surprising that treatment of these two cell lines with docetaxel ... MCF-7 cells are proficient for apoptosis but not by a caspase-3-mediated pathway (49, 51) and overexpress Bcl-2. Enhanced ...
Z-FA-FMK is inhibits effector, but not initator caspases in vitro, and suppress some forms of apoptosis 197855-65-5 sc-201303 ... Caspase-3 Inhibitor 抑制剂 Caspase-3 Inhibitor is an inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10 210344-95-9 sc- ... Caspase-1 Inhibitor II Caspase-1 Inhibitor II is an inhibitor of caspase-1, caspase-4, and caspase-5 178603-78-6 sc-300323 5 mg ... Caspase-1 inhibitor I Caspase-1 inhibitor I is an inhibitor of caspase-1, caspase-4, and caspase-5 143313-51-3 sc-358878 sc- ...
Data are means ± SEM (n = 4 mice per group). (G and H) Immunostaining for the Ki67 or cleaved caspase 3 (c-Caspase 3) in (G) ... SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila. Curr. Biol. 18, 435- ... G to I) Coimmunostaining for cleaved caspase 3 and p62 in (G) HCT-116 cells treated with VP (1 μg/ml) for 4 hours; (H) patient- ... 6, G to I). More than 70% of the cells were costained for p62 oligomerization and cleaved caspase 3 in VP-treated colon tumor ...
... caspase activation, and PARP cleavage), whereas cells harboring wild-type (wt)-FLT3 were less sensitive. In normal human blood ... factor that regulates myeloid cell proliferation and maturation and enhances the function of terminally differentiated effector ...
Alisertib kinase inhibitorRabbit polyclonal to Caspase 6. Non-selective A checkpoint system operates on the metaphase/anaphase ... Introduction Key effectors in host immune responses to intracellular pathogens are CD8+ cytolytic T lymphocytes (CTL). CTLs ... in Latin America and encourage multicentric collaborations by highlighted local research groups Rabbit polyclonal to Caspase 6 ...
... specific organ system and allosteric and redox effectors. Discovery of a new phosphotyrosine mimetic for PTP1B using breakaway ... the activation of caspase-3, and the decrease in mitochondrial transmembrane potential. ...
... mitochondrial driven apoptotic effectors. The key proteins in these two overlapping apoptotic pathways are: p53 in caspase- ... You will find two mechanisms of apoptosis induction: activation of protease-associated intracellular cascade (caspases); and ...
... might trigger caspase effector molecules [30]. Keeping all effects of VD in view we formulated protein-vitamin D-pectin nano- ... Caspases mediate confrontation to apoptosis by administration of NVD and FH535 in xenograft tumors. The result of NVD and FH535 ... PARP, a characteristic caspase substrate, is a central player of DNA repair against environmental stress and in the ... In tissue specimens from xenografts, the decreased expression of β-Catenin, and down-regulation of Cyclin D1 and caspase 3 ...
  • Molecular and genetic characterization of programmed cell death has led to the increasing appreciation of the role of interleukin converting enzyme (ICE) family of death promoting cysteine-proteases (caspases) ( 1 , 2 ). (pnas.org)
  • The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1β and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation. (ntnu.no)
  • Using yeast two-hybrid assays, we demonstrate that MRIT associates with caspases possessing large and small prodomains (FLICE, and CPP32/YAMA), as well as with the adaptor molecule FADD. (pnas.org)
  • Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. (unige.ch)
  • Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. (unige.ch)
  • The ataxia-telangiectasia mutated (ATM) kinase is a critical regulator of the response to DNA damage, acting through downstream effectors, such as p53 and checkpoint kinases (CHK) to mediate cell-cycle checkpoints in the presence of DNA damage. (aacrjournals.org)
  • Moreover transcript levels of caspase-9 associated with several clinical prognostic factors (e.g. expression of hormone receptors) in a group of untreated patients but neither with PFS nor with response to therapy. (conferenceseries.net)
  • Our results do not support a strong prognostic and/or predictive role of transcript levels of the total caspases in breast cancer patients. (conferenceseries.net)
  • Leigh ND, O'Neill RE, Du W, Chen C, Qiu J, Ashwell J, McCarthy PL, Chen G, Cao X . Host-derived CD70 suppresses murine GVHD by limiting donor T cell expansion and effector function. (umaryland.edu)
  • Gene expression pattern of total caspases and their splice variants was also determined in paclitaxel-treated MDA-MB-231 and MT-3 cell lines in vitro. (conferenceseries.net)
  • 2015). Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation. (unm.edu)
  • Cellular oxidative status (lipid peroxidation and glutathione (GSH) levels), ATP concentration, caspase-3/-7, -8 and −9 activities were determined. (biomedcentral.com)
  • Expression levels of total caspases were assessed by quantitative real-time PCR in tumors and non-neoplastic control tissues from untreated (n=100) and neoadjuvantly-pretreated (n=33) patients with breast carcinoma and compared with clinical data, response to chemotherapy and progression-free survival (PFS). (conferenceseries.net)
  • En el trabajo se detalla a nivel molecular el mecanismo por el cual ambos péptidos ejercen su acción bactericida interaccionando con la membrana bacteriana. (sebbm.es)
  • In the case of FLICE (for FADD-like ICE)/MACH (MORT1-associated CED-3 homolog) duplication of a highly conserved motif called death-effector domain (DED) is present ( 1 , 2 ). (pnas.org)
  • Results point to effectors as the agents responsible for arthropod-induced plant gall formation. (unige.ch)
  • Finally, in Aim 3 we propose to unify seemingly disparate observations into a common conceptual framework to test the hypothesis that multiple downstream effectors of Cdc42, all of which contribute to border cell migration, form an integrated network. (grantome.com)
  • A number of enzymatic systems reduce nitrite to NO and their activity and importance are defined by oxygen tension, specific organ system and allosteric and redox effectors. (pianolarge.ga)
  • On the other hand we detected differences in expression of proapoptotic and antiapoptotic isoforms for caspase-2,-3, and -9 suggesting that paclitaxel treatment influences alternative splicing of caspases and potentially cell death. (conferenceseries.net)
  • Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. (unige.ch)