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)Galactosylceramides: Cerebrosides which contain as their polar head group a galactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in beta-galactosidase, is the cause of galactosylceramide lipidosis or globoid cell leukodystrophy.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.Antigens, CD1d: A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.Natural Killer T-Cells: A specialized subset of T-LYMPHOCYTES that exhibit features of INNATE IMMUNITY similar to that of NATURAL KILLER CELLS. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D ANTIGEN.Antigens, CD1: Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.Electric Stimulation: Use of electric potential or currents to elicit biological responses.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Cells, 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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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.Receptors, Platelet-Derived Growth Factor: Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.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.Toll-Like Receptors: A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.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.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.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-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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.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.GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).Electric Stimulation Therapy: Application of electric current in treatment without the generation of perceptible heat. It includes electric stimulation of nerves or muscles, passage of current into the body, or use of interrupted current of low intensity to raise the threshold of the skin to pain.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.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.Kinetics: The rate dynamics in chemical or physical systems.Recombinant Proteins: Proteins prepared by recombinant DNA technology.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)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.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Physical Stimulation: Act of eliciting a response from a person or organism through physical contact.Deep Brain Stimulation: Therapy for MOVEMENT DISORDERS, especially PARKINSON DISEASE, that applies electricity via stereotactic implantation of ELECTRODES in specific areas of the BRAIN such as the THALAMUS. The electrodes are attached to a neurostimulator placed subcutaneously.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 enzymesCell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.Transcranial Magnetic Stimulation: A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the CEREBRAL CORTEX. It is coupled with ELECTROMYOGRAPHY response detection to assess cortical excitability by the threshold required to induce MOTOR EVOKED POTENTIALS. This method is also used for BRAIN MAPPING, to study NEUROPHYSIOLOGY, and as a substitute for ELECTROCONVULSIVE THERAPY for treating DEPRESSION. Induction of SEIZURES limits its clinical usage.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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Transcutaneous Electric Nerve Stimulation: The use of specifically placed small electrodes to deliver electrical impulses across the SKIN to relieve PAIN. It is used less frequently to produce ANESTHESIA.Mice, Inbred C57BLRNA, 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Photic Stimulation: Investigative technique commonly used during ELECTROENCEPHALOGRAPHY in which a series of bright light flashes or visual patterns are used to elicit brain activity.Electrodes, Implanted: Surgically placed electric conductors through which ELECTRIC STIMULATION is delivered to or electrical activity is recorded from a specific point inside the body.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.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.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.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Acoustic Stimulation: Use of sound to elicit a response in the nervous system.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.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.Membrane 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.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.CD30 Ligand: A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Evoked Potentials: Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Evoked Potentials, Motor: The electrical response evoked in a muscle or motor nerve by electrical or magnetic stimulation. Common methods of stimulation are by transcranial electrical and TRANSCRANIAL MAGNETIC STIMULATION. It is often used for monitoring during neurosurgery.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.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.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.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.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.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.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.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.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.OX40 Ligand: A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Afferent Pathways: Nerve structures through which impulses are conducted from a peripheral part toward a nerve center.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.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)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.Motor Cortex: Area of the FRONTAL LOBE concerned with primary motor control located in the dorsal PRECENTRAL GYRUS immediately anterior to the central sulcus. It is comprised of three areas: the primary motor cortex located on the anterior paracentral lobule on the medial surface of the brain; the premotor cortex located anterior to the primary motor cortex; and the supplementary motor area located on the midline surface of the hemisphere anterior to the primary motor cortex.Subthalamic Nucleus: Lens-shaped structure on the inner aspect of the INTERNAL CAPSULE. The SUBTHALAMIC NUCLEUS and pathways traversing this region are concerned with the integration of somatic motor function.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Mice, Inbred BALB CMuscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.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.Self Stimulation: Stimulation of the brain, which is self-administered. The stimulation may result in negative or positive reinforcement.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.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Cell Adhesion: Adherence of cells to surfaces or to other cells.Electrodes: Electric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Motor Neurons: Neurons which activate MUSCLE CELLS.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.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.)Evoked Potentials, Somatosensory: The electric response evoked in the CEREBRAL CORTEX by stimulation along AFFERENT PATHWAYS from PERIPHERAL NERVES to CEREBRUM.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)4-1BB Ligand: A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Oligopeptides: Peptides composed of between two and twelve amino acids.Spinal Cord Stimulation: Application of electric current to the spine for treatment of a variety of conditions involving innervation from the spinal cord.Reaction Time: The time from the onset of a stimulus until a response is observed.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.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.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.Muscles: Contractile tissue that produces movement in animals.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.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Parasympathetic Nervous System: The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC, 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.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.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.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Neural Pathways: Neural tracts connecting one part of the nervous system with another.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Neuronal Plasticity: The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.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).Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Functional Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Ovulation Induction: Techniques for the artifical induction of ovulation, the rupture of the follicle and release of the ovum.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.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.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.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Spleen: An encapsulated lymphatic organ through which venous blood filters.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.Somatosensory Cortex: Area of the parietal lobe concerned with receiving sensations such as movement, pain, pressure, position, temperature, touch, and vibration. It lies posterior to the central sulcus.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Splanchnic Nerves: The major nerves supplying sympathetic innervation to the abdomen. The greater, lesser, and lowest (or smallest) splanchnic nerves are formed by preganglionic fibers from the spinal cord which pass through the paravertebral ganglia and then to the celiac ganglia and plexuses. The lumbar splanchnic nerves carry fibers which pass through the lumbar paravertebral ganglia to the mesenteric and hypogastric ganglia.Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.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.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.PhosphoproteinsHydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Prior to ligand stimulation most RTKs present as a monomer on the surface of cells. Ligand binding to the extracellular domain ... Following ligand binding, a conformational change occurs in the EGFR monomers. This leads to EGFR dimerization. Dimerization ... An example of RTKs that undergo autophosphorylation is the Epidermal Growth Factor receptor (EGFR ). EGFR was the first ... Src kinases are involved in intracellular signaling pathways that influence cell growth and cell adhesion strength. The latter ...
... naturally occurring cell death), trophic factor withdrawal-induced cell death, the spontaneous regression characteristic of ... A trophic ligand is a molecule whose protein binding stimulates cell growth, differentiation, and/or survival. Cells depend for ... Androgen Receptor Some integrins NTRK3 Cells depend for their survival on stimulation that is mediated by various receptors and ... in the absence of ligand, the receptors initiate and/or amplify a signal for programmed cell death. Thus cells that express ...
The olfactory stimulation can occur before or during the episode of taste stimulation. The dual perception of the stimulus ... Taste-odor integration occurs at earlier stages of processing. By life experience, factors such as the physiological ... The transduction of light into neural activity occurs via the photoreceptor cells in the retina. When there is no light, ... Most of the receptors are dedicated to detect repulsive ligand. Perceptions of taste is generated by the following sensory ...
These factors are usually produced by the newly activated T helper cell.[22] However, this activation occurs only after the B ... Activation of B cells.. Complete stimulation of T helper cells requires the B7 molecule present on the antigen presenting cell ... called ligand) that binds specifically to cluster of differentiation 4 would be known as CD4+ cell. Likewise, a CD8+ cell is ... Costimulation of B cell by activated T helper cell[edit]. For more details on activation of B cells, see B cell § ...
RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1 ... NFATc1 stimulation, however, begins ~24-48 hours after binding occurs and its expression has been shown to be RANKL dependent. ... receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins ... Väänänen H, Zhao H, Mulari M, Halleen J (2000). "The cell biology of osteoclast function". J Cell Sci. 113 (3): 377-81. PMID ...
However, it is required for B cell proliferation induced by stimulation of TLR3 and TLR4. Activation of nuclear factor kappa B ... Upon stimulation by the Fas ligand, the Fas receptor trimerises. Many receptors, including Fas, contain a cytoplasmic DD and ... "Inhibition of death receptor-mediated gene induction by a cycloheximide-sensitive factor occurs at the level of or upstream of ... In contrast, FADD has no effect on the proliferation of B cells induced by stimulation of the B cell receptor. ...
In glioma cells, the effects of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) have been shown to induce DISC- ... Once the DISC assembles, it allows APO-1 signaling to occur, which triggers cell death. In order to do this, downstream targets ... as c-FLIPS is upregulated upon stimulation of the T cell receptor. Furthermore, as high expression of FLIP is known to promote ... The entire process is initiated when the cell registers the presence of CD95L, the cognate ligand for APO-1. Upon binding, the ...
... secretion may occur in many tissues. Endocrine glands are the cardinal example, but specialized cells in various other ... These receptors belong to the nuclear receptor family of ligand-activated transcription factors. To bind their receptors, these ... Hormones have the following effects on the body: stimulation or inhibition of growth wake-sleep cycle and other circadian ... Hormones affect distant cells by binding to specific receptor proteins in the target cell resulting in a change in cell ...
RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1 ... NFATc1 stimulation, however, begins ~24-48 hours after binding occurs and its expression has been shown to be RANKL dependent. ... receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins ... Väänänen HK, Zhao H, Mulari M, Halleen JM (February 2000). "The cell biology of osteoclast function". Journal of Cell Science. ...
At the neuronal cell body, a process called chromatolysis occurs in which the nucleus migrates to the periphery of the cell ... Electrical stimulation can promote nerve regeneration[citation needed]. The frequency of stimulation is an important factor in ... In general they are protein ligands for tyrosine kinase receptors; binding to the specific receptor yields autophosphorylation ... Schwann cells play an important role in not only producing neurotrophic factors such as nerve growth factor (NGF) and ciliary ...
... or movement to cause a change in the excitability of specialized sensory cells and sensory neurons. The stimulation of a ... In addition to binding to ECM ligands, integrins are also receptive to autocrine and paracrine signals such as growth factors ... Some intracellular processes that have been observed to occur within these pathways include phosphorylation of ERK1/2, p38 MAPK ... transcription factors, cytokines and growth factors. The balance that is struck between anabolic and catabolic processes is ...
Another example occurs in activated T cell lymphocytes, i.e., when a T cell is induced to mature by binding to a peptide:MHC ... For example, despite widespread expression of epidermal growth factor receptors (EGFRs) and EGF family ligands in non-small- ... causing self-stimulation and ultimately a monoclonal population of T cells. These T cells can then go on to perform effector ... Paracrine signaling is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, ...
RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1 ... NFATc1 stimulation, however, begins ~24-48 hours after binding occurs and its expression has been shown to be RANKL dependent. ... receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins ... When the surgical instrument went out of use, the cell became known by its present name. Giant osteoclasts can occur in some ...
Tumor necrosis factors (TNF) (and other cytokines) are produced by cells of the innate immune system during local injury and ... Stimulation of the efferent vagus nerve slows heart rate, induces gastric motility, and inhibits TNF production in spleen. ... Ligand receptor signaling does suppress production of anti-inflammatory cytokines (IL-10). Rosas-Ballina M, Ochani M, Parrish ... pathway provides a braking effect on the innate immune response which protects the body against the damage that can occur if a ...
... is found to mediate the adhesion of tumor cells to endothelial cells, by binding to E-selectin ligands on the tumor ... Maximal expression of E-selectin occurs around 6-12 hours after cytokine stimulation, and levels returns to baseline within 24 ... E selectin has a cassette structure: an N-terminal, C-type lectin domain, an EGF (epidermal-growth-factor)-like domain, 6 Sushi ... E-selectin mediates the adhesion of tumor cells to endothelial cells, by binding to E-selectin ligands expressed by neutrophils ...
4,5) CD134 is predominantly found on activated T cells and binds to OX40 ligand, causing T-cell stimulation, proliferation, ... Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of ... False positives occur when the cat carries the antibody (which is harmless) but does not carry the actual virus. The most ... of the virus and the target cells' surface receptors. First the SU glycoprotein binds to CD134, a receptor on the host cell. ...
... tumour necrosis factor (TNF); chemokines: chemokines ligand 2, CCL5, CXC-chemokine ligand 1 (CXCL1); as well as macrophage ... "Stimulation of smooth muscle cell proliferation by ox-LDL- and acetyl LDL-induced macrophage-derived foam cells". Life Sciences ... Autoimmunity occurs when the body starts attacking itself. The link between atherosclerosis and autoimmunity is plasmacytoid ... Foam cell formation is triggered by a number of factors including the uncontrolled uptake of modified low density lipoproteins ...
Ligands do not bind to NGFIB, so modulation occurs at the level of protein expression and posttranslational modification. Nerve ... "Dual roles of Nur77 in selective regulation of apoptosis and cell cycle by TPA and ATRA in gastric cancer cells". ... Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. ... Nerve growth factor IB is a member of the Nur nuclear receptor family of intracellular transcription factors. NGFIB is involved ...
As cells leave the S phase and enter the G2 phase, a massive tyrosine phosphorylation of p34cdc2 occurs. Regulation with ... Tyrosine phosphorylation of certain target proteins is required for ligand stimulation of their enzymatic activity. In response ... that negatively regulates the anti-proliferative function of transforming growth factor beta (TGF-beta) in endothelial cells. ... For example, p140Cap (Cas-associated protein) are phosphorylated within 15 minutes of cell adhesion to integrin ligands. ...
... and squamous cell carcinoma occurred in 15 (88.2%), 12 (70.6%) and 3 (17.7%) out of 17 rats respectively. After 60 days, the ... This causes the nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated response pathway to induce antioxidant responses. ... AhR ligands can induce formation of an AhR-estrogen receptor (ER) complex. 3-MC was found to elicit estrogenic activity by this ... mechanism, and by stimulation of the expression of some endogenous ER target genes. 3-MC may cause respiratory tract irritation ...
... and Fas ligand (FasL, CD95 ligand). It occurs as a result of repeated stimulation of specific T-cell receptors (TCR) and it ... Necrosis is cell death caused by external factors such as trauma or infection, and occurs in several different forms. Recently ... doi:10.1016/j.cell.2012.03.042. Zhang J, Xu X, Liu Y. (2004), Activation-Induced Cell Death in T Cells and Autoimmunity. Cell ... Kinds of cell death include the following: Programmed cell death (or PCD) is cell death mediated by an intracellular program. ...
... release histamine that stimulates nearby parietal cells by binding to the apical H2 receptor. Stimulation of the parietal cell ... Histamine release occurs when allergens bind to mast-cell-bound IgE antibodies. Reduction of IgE overproduction may lower the ... endothelium-derived hyperpolarizing factors and other compounds from the endothelial cells. Increased vascular permeability ... As of 2015, histamine is believed to activate ligand-gated chloride channels in the brain and intestinal epithelium. Although ...
Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. ... Expression of neurotrophin receptors, TrkA and TrkC, is sufficient to induce apoptosis in the absence of their ligands. ... Decreased workload Loss of innervation Diminished blood supply Inadequate nutrition Loss of endocrine stimulation Senility ... An atrophic factor is a force that causes a cell to die. Only natural forces on the cell are considered to be atrophic factors ...
Van de Vijver M, Kumar R, Mendelsohn J. Ligand-induced activation of A431 cell EGF receptors occurs primarily by an autocrine ... Growth stimulation of A431 cells by EGF: Identification of high affinity receptors for epidermal growth factor by an anti- ... had an international reputation for his research on how the binding of growth factors to cell-surface receptors regulates cell ... factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor- ...
Unlike other tyrosine-kinase receptors, maximal activation of receptors occurs 18 hours after collagen stimulation. They ... It is expressed mainly in epithelial cells and leukocytes and expression rate changes due to cell cycle phase.Functions include ... A ligand of Lair-1 receptor is type XVII transmembrane collagen, it binds type I and III collagen as well. Collagen binding ... This interaction activates signalling cascades leading to coagulation factors release. Mainly fibrillar collagens type I and ...
This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial ... Different ligands are used for different imaging purposes, depending on what the radiologist/researcher wants to detect. Three- ... One of the factors most responsible for the acceptance of positron imaging was the development of radiopharmaceuticals. In ... Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred (i.e ...
... cell cycle progression, and morphology, although unlike mating, pseudohyphal differentiation occurs only in diploid cells. ... Finally, the Gpr1p ligand could be a compound that is rapidly produced and secreted following glucose readdition. Yeast cells ... 1993 Polarization of yeast cells in spatial gradients of α mating factor. Proc. Natl. Acad. Sci. USA 90: 8332-8336. ... 1993 Analysis of inositol metabolites produced by Saccharomyces cerevisiae in response to glucose stimulation. J. Biol. Chem. ...
The stimulation of PPARγ by ADD1/SREBP1 does not require coexpression in the same cells; supernatants from cultures that ... to arginine converts ADD1/SREBP1 into a pure E-box binding factor and hence allows discrimination of those functions that occur ... there appears to be at least 8-fold more ligand activity in cells that were transfected with ADD1. C/EBPα-transfected cells ... C) Ligand activity from cells transfected with either empty vector, ADD1, ADD1-R, or ADD1-DN. Conditions were the same as in A. ...
The epidermal growth factor receptor (EGFR) pathway plays prominent roles in regulating cell growth, apoptosis, and ... and ligand-independent constitutive stimulation signaling loops, and has been implicated in several human tumors, including ... differentiation, a process that is tightly regulated in normal epithelial cells (12). Deregulation of this pathway can occur, ... Genetic polymorphisms of the epidermal growth factor and related receptor in non-small cell lung cancer-a review of the ...
... produces IGF-1 for paracrine stimulation (18) . When the ligand binds to IGF-1R, signaling occurs through Ras-dependent ... Melanoma cells do not express IGF-1, excluding this growth factor from autocrine stimulation. Although all melanoma cells ... suggesting the absence of an autocrine loop for this growth factor in melanoma cells. The stimulation of melanoma cells by IGF- ... However, the cells can be rescued by IGF-1, suggesting that IGF-1 is a survival factor for them. Cell survival by IGF-1 is most ...
... reports that over 300 ng/ml are needed to yield maximum stimulation of hematopoietic stem cell self-renewal by the flt-3 ligand ... For primary cell cultures in which microenvironmental factors are important, the location of a cell relative to the walls of ... The effective communication distance ζ0.5 is indicated where the c/Km curve at time τ0.5 drops below unity, which occurs at: 14 ... the effective communication distance would increase by a factor of 4 compared with a suspended cell. Likewise, a cell in a ...
J Cell Biol. 2011 Jul 11;194(1):7-15. doi: 10.1083/jcb.201102095. Research Support, N.I.H., Intramural; Research Support, Non-U ... Shown here is the signaling pathway envisioned to result after growth factor (GF) stimulation. Ligand binding to its receptor ... This Prx1 inactivation only occurs in the region surrounding the stimulated growth factor, thus allowing for the local ... Antioxidant proteins can regulate signaling pathways. Proteins like thioredoxin (Trx) can function in cells to maintain redox ...
Prior to ligand stimulation most RTKs present as a monomer on the surface of cells. Ligand binding to the extracellular domain ... Following ligand binding, a conformational change occurs in the EGFR monomers. This leads to EGFR dimerization. Dimerization ... An example of RTKs that undergo autophosphorylation is the Epidermal Growth Factor receptor (EGFR ). EGFR was the first ... Src kinases are involved in intracellular signaling pathways that influence cell growth and cell adhesion strength. The latter ...
Sympathetic stimulation of osteoblasts increases expression of the receptor activator of nuclear factor B ligand (RANKL). The ... The leptin dependent regulation of bone mass occurs through via the β2-adrenergic receptor as β2-adrenergic receptor-null mice ... Following stimulation, cells were immediately washed with sterile PBS and protein extracted using the CNMCS compartmental ... Cells were cultured at a concentration of 1 × 105 as a monolayer for 5 days in 55 mm tissue culture Petri dishes. The cells ...
PKCbeta is highly expressed in brain and hematopoietic cells. Autophosphorylation of PKCbeta occurs at the N- and C-terminal ... The PKC pathway represents a major signal transduction system that is activated following ligand-stimulation of transmembrane ... receptors by hormones, neurotransmitters and growth factors. ... PKCbeta is critical for the proliferation of K562 cells, as ... Molecular biology of the cell, Vol. 12, Issue 7, pp. 1973-82, 2001 (PubMed). Stebbins, Mochly-Rosen: "Binding specificity for ...
... forkhead box P3/CD25 double-positive T regulatory cells are associated with the increased nuclear factor-kappaB ligand (RANKL+ ... The initial activation of the host response occurs through stimulation of toll-like receptors (TLRs) and nucleotide-binding ... The predominant cell types in endodontic lesions in a rat model were shown to be T-cells followed by B-cells and monocytes/ ... gingival epithelial cells, endothelial cells, and inflammatory cells (62). Prostaglandin E2 production is elevated in ...
2004 The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry. Curr. Biol. 14, 685-690 ... Extracellular ligand stimulation of these receptors activates a PI-specific phospholipase C (PLC). Activated PLC converts ... In non-excitable (non-neuronal) cells, a majority of intracellular Ca2+ release occurs through inositol 1,4,5-trisphosphate (IP ... Calcium imaging in cell-cell signaling. In Developmental biology protocols Tuan R.S, Lo C.W vol. 1 2000pp. 253-261. Eds. Totowa ...
... effects of PEDF occur through stimulation of the Fas/Fas ligand-mediated apoptotic pathway which targets the endothelial cells ... Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion ... and the principal angiogenic factor, vascular endothelial growth factor (VEGF), is highly expressed by ganglion cells in the ... the majority of cells in the macula have exited the cell cycle and differentiated as neurons, while the majority of cells in ...
FL shows synergistic stimulation of normal hematopoietic stem/progenitor cells when combined with other growth factors. ... In conclusion, coexpression of FLT3 receptor and its ligand, FL, occurs in a high percentage of primary AML cases and in one ... c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood. 1998;91: 1101-1134. ... Pietsch T. Paracrine and autocrine growth mechanisms of human stem cell factor (c-kit ligand) in myeloid leukemia. Nouv Rev Fr ...
DCs to activate NK cells via IL-15 transpresentation occurs in an IFN-dependent fashion following stimulation with TLR ligands ... and IFN regulatory factor element (21, 22). Although injections of polyinosinic-polycytidylic acid or IFN-α both induce IL-15 ... T cells, B cells, and NK cells were eliminated from the analysis by first gating on those cells negative for expression of CD3 ... conventional dendritic cell. DC. dendritic cell. EmGFP. emerald GFP. iEC. intestinal epithelial cell. IEL. intraepithelial ...
Conditional Knockdown of Gene Expression in Cancer Cell Lines to Study the Recruitment of Monocytes/Macrophages to the Tumor ... cells increase the expression of interleukin-6 by bone marrow stromal cells and that stimulation does not require cell-cell ... Activation occurs via the receptor activator of NFkappaB ligand (RANKL) or in the absence of RANKL via activation of bone ... Contact between tumor cells and the ECM or stromal cells as well as the production of soluble factors and microvesicles all ...
... and both ligand-dependent malignant transformation and increased cell growth occur in cultured breast cells overexpressing the ... enhancing growth factor-dependent cell proliferation and/or by directly affecting cell metabolism.(2)Insulin increases the ... the INSR can exert its oncogenic potential in malignant cells via abnormal stimulation of multiple cellular signaling cascades ... R. Drakas, X. Tu, and R. Baserga, "Control of cell size through phosphorylation of upstream binding factor 1 by nuclear ...
Upon ligand stimulation, Smads move into the nucleus and function as components of transcription complexes. TGF-beta and BMP ... Negative regulation occurs at the extracellular, membrane, cytoplasmic and nuclear levels. TGF-beta and BMP signaling is often ... Cytokines of the transforming growth factor beta (TGF-beta) superfamily, including TGF-betas, activins and bone morphogenetic ... Building a plant cell wall. In their Cell Science at a Glance article and accompanying poster, Staffan Persson and colleagues ...
... achieved by the removal of diseased and damaged hepatocytes and their coordinated replacement to maintain a constant liver cell ... Cell Line, Tumor. Fas Ligand Protein. Hepatocytes / cytology*, physiology. Liver Neoplasms. Membrane Glycoproteins / deficiency ... The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known to influence apoptosis, conceivably by ... present evidence demonstrating that AhR expression and function promote apoptosis in liver cells in response to Fas stimulation ...
... but many questions remain as to how current models of NF-κB signaling and dynamics can be translated to innate immune cells ... bringing us closer to a more complete understanding of inflammatory transcription factor dynamics and how different cellular ... but many questions remain as to how current models of NF-κB signaling and dynamics can be translated to innate immune cells ... bringing us closer to a more complete understanding of inflammatory transcription factor dynamics and how different cellular ...
Ligand stimulation was terminated by two washes with ice-cold PBS (pH 7.4), removal of excess liquid by aspiration, and ... The opposite occurs with increased SR levels. Intracellular factors (like cyclic AMP) (44) and extracellular conditions (like ... cells indicate that these cells fail to proliferate in response to growth factors (49). However, when cells are transfected ... In contrast to results obtained with R−/IR-A cells, in R− cells transfected with IR-B (R−/IR-B cells) IGF-II inhibited labeled ...
The stimulation of the TIR domain occurs upon ligand binding and activation of the receptors and results in the relay of a ... and epidermal growth factor (5 ng/ml). The 1198 cells and the 1170-I cells were grown in keratinocyte serum-free medium ... and tumorigenic cell lines derived from NHBE cells and six NSCLC cell lines. The NHBE-derived cell lines represent an in vitro ... Andres J. P. Klein-Szanto (Fox Chase Cancer Center, Philadelphia, PA). NHBE cells, the BEAS-2B cells, and the 1799 cells were ...
... also occurs upon stimulation of the transmembrane isoform of CD16 (Fc gamma RIIIA) in NK cells and in a T cell line expressing ... for the Fc gamma R-dependent induction of c-fos and tumor necrosis factor alpha mRNA expression in monocytes and NK cells. ... transfected Fc gamma RIIIA alpha ligand-binding chain in association with zeta, but not upon stimulation of the glycosil- ... cells. Our results indicate that occupancy of Fc gamma RI and Fc gamma RII on the monocytic cell line THP-I and on ...
To further evaluate epicardial cell responses to PDGF ligand stimulation, we used a wound-closure assay on epicardial ... cell migration in mice bearing signaling point mutants of PDGFRβ. Previous analyses have shown that cVSMC development occurs ... Transforming growth factor-beta induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells ... Figure 5. PDGFRβ stimulation induces epicardial cell migration. A, Quantification of WT1+ cells in right and left lateral ...
This redistribution away from the cell periphery did not occur in the absence of ligand addition, and SU5402, a potent ... 14 cells). (C) Eps8 knockdown and vector control HeLa cells transiently expressing FGFR2-GFP were lysed following stimulation ... Growth factor receptors undergo regulated internalization from the cell surface in response to ligand binding (von Zastrow and ... The splicing co-factor Barricade/Tat-SF1 is required for cell cycle and lineage progression in Drosophila neural stem cells. ...
Deregulation of E2F family transcription factors is associated with cancer progression and metastasis. Here, the authors ... whereas stimulation with EGFR ligand has no effect on cell invasion. In contrast, EGFR stimulation of MCF-7 cells promotes cell ... d Boyden assay indicating the invasive potential of epithelial cell lines after stimulation with growth factors and/or ... Figure 5d demonstrates that the in silico predicted selective response to the different stimuli actually occurs: In RT-4 cells ...
  • TLR3, TLR7/8, and TLR9 recognize the nonself-nucleic acid moieties dsRNA, ssRNA, and hypomethylated CpG DNA, respectively, whereas TLR4 recognizes viral glycoproteins and the viral ligand for TLR2 remains to be identified. (
  • To discriminate between self and non-self nucleic acids, the nucleic acid-sensing TLRs 3, 7, 8, and 9 are expressed only within the cell interior, contrasting with other TLRs (for example, TLR2 or TLR4) that are expressed on cell surfaces. (
  • Transient TLR4-MyD88 complexes appeared during the first hour after lipopolysaccharide stimulation, and TLR4-4-1BBL interactions were detected between 2 h and 8 h after lipopolysaccharide stimulation. (
  • Periapical lesions of endodontic origin and periodontitis are two common conditions found in the oral cavity that share pathologic mechanisms involving interactions between immune cells and bone. (
  • Dendritic cells (DCs) and other APCs such as macrophages help maintain the homeostasis of immune cells. (
  • The dynamics by which NF-κB proteins shuttle between the cytoplasm and the nucleus to initiate transcription have been studied rigorously in fibroblasts and other non-hematopoietic cells, but many questions remain as to how current models of NF-κB signaling and dynamics can be translated to innate immune cells such as macrophages. (
  • We will end by looking ahead to how new techniques and technologies should allow us to analyze these signaling processes with greater clarity, bringing us closer to a more complete understanding of inflammatory transcription factor dynamics and how different cellular contexts might allow for appropriate control of innate immune responses. (
  • In this review, we will focus on the innate immune aspects of NF-κB signaling, especially in the mononuclear myeloid cell compartment, where NF-κB regulates thousands of primary and secondary response genes including cytokines, chemokines, transcription factors, antimicrobial peptides, and interferon (IFN)-stimulated genes (ISGs) ( 10 - 14 ). (
  • Here we show that contact-dependent interactions between activated human NK cells and immature DCs (iDCs) provides a "control switch" for the immune system. (
  • Cooperation between distinct immune cells and reciprocal coordination of their responses provides a robust mechanism for regulating the initiation and amplification of an immune response. (
  • We reasoned that NK cells may perform an analogous function during the initial phase of an immune response before activated T cells are generated. (
  • The 1,25(OH) D -dependent transcriptome of THP-1 cells comprised 587 genes, 311 of which were primary targets with main functions in the immune system. (
  • This occurs in the lymphoid tissues or the central immune environment. (
  • Recognition of the tumor antigens as non-self by the T cells results in generation of the first signal for an anti-tumor immune response to proceed. (
  • Imbalances in these immune regulatory signals occur in pathological conditions characterized by chronic antigenic stimulation. (
  • Clinical studies often rely on the use of cryopreserved peripheral blood mononuclear cells (PBMC) to evaluate cellular immune responses. (
  • Immune function studies employing cryopreserved cells may lead to increased T-cell effector cytolytic and regulatory immune responses. (
  • Clinical studies often rely on cryopreserved cells in order to monitor immune function. (
  • MSCs have also been reported to support hematopoiesis and suppress immune reaction after cell/organ transplantation [ 11 - 14 ]. (
  • Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals . (
  • a key feature of this response is the production of antibodies by B cells (or B lymphocytes) involving an arm of the immune system known as humoral immunity . (
  • The collection of various cells , tissues and organs that specializes in protecting the body against infections is known as the immune system . (
  • Immune cell subsets and receptor expression were extensively characterized by quantitative flow cytometry. (
  • Therapy that reverses T cell exhaustion may restore immune function in immunocompromised patients and improve survival in sepsis. (
  • Studying macrophage biology in the context of a whole living organism provides unique possibilities to understand the contribution of this extremely dynamic cell subset in the reaction to infections, and has revealed the relevance of cellular and molecular processes that are fundamental to the cell-mediated innate immune response. (
  • Macrophages and neutrophils are the main phagocytic cell types of the innate immune system. (
  • However, because innate recognition of disease-specific antigens is a prerequisite for adaptive immune responses to occur, we begin by briefly introducing atherosclerosis-relevant antigens recognized by innate immunity. (
  • In 2011, a team of Fred Hutch researchers from the Spies Lab in the Clinical Research Division published unexpected findings regarding the stimulatory lymphocyte receptor NKG2D, a well-known mediator of immune surveillance of malignant cells. (
  • Signal-triggering molecules that bind to this receptor, NKG2D ligands, are generally not expressed on the surface of normal cells but are induced in most types of cancers, making them a target for cancer-fighting immune cells. (
  • The ability of cancer cells to hijack an important part of our immune system adds a "provocative twist" to our current knowledge. (
  • NKG2D and its ligands are considered central innate immune regulators of successful and/or failed tumor immune surveillance. (
  • chronic lymphocytic leukemia-secreted cytokines, such as interleukin-10, suppress cytotoxic T-cell functions, while chronic lymphocytic leukemia-associated monocyte-derived cells contribute to suppression of T-cell function by producing the immune checkpoint factor, programmed cell death-ligand 1. (
  • Specifically, microbial and dietary factors incurred by diet-induced obesity influence underlying innate and adaptive responses of the intestinal immune system. (
  • This chapter does not attempt to be exhaustive, but rather uses selected examples to illustrate this process (see Thyrotropin-Releasing Hormone: Focus on Basic Neurobiology , Corticotropin-Releasing Factor: Physiology, Pharmacology, and Role in Central Nervous System and Immune Disorders , Neuroendocrine Interactions , Stress , and The Role of Acetylcholine Mechanisms in Mood Disorders for related topics). (
  • Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. (
  • May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). (
  • A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. (
  • Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells. (
  • 1 . A method for reducing an immune response against an alloantigen, comprising: contacting immune effector cells with at least one member selected from the group consisting of mesenchymal stem cells and a supernatant from a mesenchymal stem cell culture in an amount effective to reduce the immune response. (
  • 22 . A method of reducing an immune response caused by a donor transplant, comprising contacting the transplant with tissue obtained from the transplant recipient and then contacting the donor transplant with mesenchymal stem cells in an amount effective to reduce an immune response against the recipient by the donor transplant. (
  • In earlier studies, we were able to demonstrate a new superfusion technique to investigate the close interaction between autonomic presynaptic nerve terminals (and their transmitters) and immune-competent cells in the murine spleen ( 27-29 ). (
  • Recent in vitro data from our laboratory have shown the loss of E2 dependence and the acquisition of Tam resistance following the transfection of HRGβ2 cDNA into MCF-7 cells, an E2-dependent breast cancer cell line ( 10 ). (
  • It is known that the in vitro interaction of human NK cells with autologous DCs results in DC lysis. (
  • To address this hypothesis we developed an in vitro model to dissect the potential interactions between autologous NK cells and immature DCs (iDCs) * in the presence or absence of limiting concentrations of a bacterial stimulus (LPS). (
  • Taxane-sensitive (SKOV3ip1 and HeyA8) and taxane-resistant (HeyA8-MDR) cell lines were used for in vitro and in vivo therapy experiments using TAE226 alone and in combination with docetaxel. (
  • We tested their effectiveness in autoimmune B cells and interferon-alpha-producing dendritic cells in vitro and in lupus-prone MRL-Fas lpr / lpr mice in vivo . (
  • Functional assays revealed impaired secretion of interferon γ following stimulation in vitro , which was reversible by incubation overnight in fresh media. (
  • Hence, the functional consequence of the up-regulation of TACI on NOD B cells was analysed both in vitro and in vivo. (
  • When tested for motility, i.e. ability to move spontaneously and actively, the NKG2D-DAP10-expressing cells migrated 6 to 12 times more than the control cells through various membranes in vitro . (
  • Here we tested this hypothesis in vitro by examining the stimulatory effects of CpG RNA sequences in plasmacytoid dendritic cells (pDCs) ( 22 ). (
  • Ectopic expression of constitutive STAT3 is sufficient to induce transformation of rodent cells in vitro and tumor formation in vivo [ 3 , 13 ]. (
  • Using an in vitro coculture system composed of 3T3-L1 adipocytes and RAW264 macrophages, we previously demonstrated that saturated fatty acids (FAs) and tumor necrosis factor (TNF)-α derived from adipocytes and macrophages, respectively, play a major role in the coculture-induced inflammatory changes. (
  • thus, an intact anion secretion and fluid flow occurs. (
  • Fecal elastase levels and pancreatic enzyme secretion in response to stimulation testing may also be reduced. (
  • B cells have many different roles in systemic lupus erythematosus (SLE), ranging from autoantigen recognition and processing to effector functions (for example, autoantibody and cytokine secretion). (
  • This extensively folded or ruffled border facilitates bone removal by dramatically increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast that is actively resorbing bone. (
  • The present study uses a solitary cell model to estimate effective communication distances over which a single cell can meaningfully propagate a soluble signal. (
  • Plasma levels of β 2 microglobulin and soluble Fas, Fas ligand, CD8, CD4, and TNF receptor were increased, and soluble CD8 was higher in boys than in girls. (
  • The antibodies are soluble and do not require direct cell-to-cell contact between the pathogen and the B-cell to function. (
  • Their soluble forms which carry out these functions are produced by plasma B cells , a type of white blood cell. (
  • Anesthetized cats were treated with saline, a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig), or an E- and L-selectin antibody (EL-246) before exposure and occlusion of a jugular vein. (
  • 9 . A method for inducing hemostasis in a subject, comprising administering to said subject a soluble P-selectin polypeptide, such that hemostasis occurs. (
  • 10 . A method for inducing hemostasis in a subject, comprising administering to said subject an isolated nucleic acid molecule comprising a nucleotide sequence which encodes a soluble P-selectin polypeptide, such that hemostasis occurs. (
  • Alternatively, limiting IL-15 expression to DCs can partially restore the defect within the NK cell and CD8 + memory T cell populations but fails to rescue IEL subsets ( 6 ) that require IL-15 production specifically from intestinal epithelial cells (iECs) ( 7 ). (
  • Urine samples from healthy control subjects ( n = 50) and type 2 diabetic patients ( n = 100) were collected and tested for excretion of CML and the presence of proximal tubular epithelial cells (pTECs). (
  • A cell's ability to propagate signals to neighboring cells and receive signals from them is critical in this process. (
  • After fertilization, the next major developmental programme involves the establishment of the primary axes, in which regions of the embryo receive signals to determine the cells that will contribute to the dorsal (back) or ventral (belly) tissue as well as anterior (head/top) and posterior (tail/bottom) regions. (
  • Thus melanoma cells remain sensitive to negative growth regulatory signals originating from fibrillar collagen, and the proteolytic degradation of fibrils is a mechanism allowing tumor cells to escape these restrictive signals. (
  • How does a cell in an organism differentiate signals from noise while being immersed in bath of growth factors and hormones? (
  • The really important discovery is that the primary cilium detects signals, which tell the cells to engage their compass reading and move in the right direction to close the wound," Christensen explains. (
  • In mutant cells that lack the primary cilium," Christensen says, "cell migration is unregulated with uncontrolled directional cell displacement during wound closure, leaving the cells blindfolded to some of the signals that permit the cells to navigate correctly. (
  • Further, we study signals involved in fine-tuning expression levels of individual target genes, specifically the role of DNA as a ligand that allosterically modulates the activity of GR. (
  • Interestingly, many of these sequence signals are cell type specific and functional studies using transcriptional reporters indicate that they play a critical role in directing cell-type specific transcriptional regulation by GR. (
  • This, associated with increased enzymatic activity, also occurs upon stimulation of the transmembrane isoform of CD16 (Fc gamma RIIIA) in NK cells and in a T cell line expressing transfected Fc gamma RIIIA alpha ligand-binding chain in association with zeta, but not upon stimulation of the glycosil-phosphatidylinositol-anchored Fc gamma RIIIB on PMN. (
  • NFATc1 stimulation, however, begins ~24-48 hours after binding occurs and its expression has been shown to be RANKL dependent. (
  • In the present study, we investigated whether hypoxia regulates RANKL expression in ATDC5 cells, a murine chondrogenic cell line, and hypoxia-inducible factor-1α (HIF-1α) mediates hypoxia-induced RANKL expression by transactivating the RANKL promoter. (
  • HIF-1α increased RANKL promoter reporter activity in a HIF-1α binding element-dependent manner in ATDC5 cells. (
  • Hypoxia-induced RANKL levels were much higher in differentiated ATDC5 cells, as compared to proliferating ATDC5 cells. (
  • Activated stromal fibroblasts can in turn secrete growth factors that support tumor growth. (
  • Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. (
  • The availability of mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells marked a major milestone in stem cell therapies [ 1 , 2 ]. (
  • These membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts , thus requiring direct contact between these cells and osteoclast precursors . (
  • Finally, we demonstrate directly that cells expressing ADD1/SREBP1 produce and secrete lipid molecule(s) that bind directly to PPARγ, displacing the binding of radioactive thiazolidinedione ligands. (
  • In the presence of an appropriate activating stimulus, these molecules bind more strongly and arrest the cell (6). (
  • Kelso, A & Owens, T 1988, ' Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody ', Journal of Immunology , bind 140, nr. 4, s. 1159-67. (
  • miRNAs bind to complementary sequences in the 3'-untranslated region (3'-UTR) of the target gene transcripts and regulate their gene expression and function including apoptosis of tumor cells [ 12 ]. (
  • Ligands that bind to the receptor and block the binding of agonists but that do not activate changes are known as antagonists. (
  • Consequently, the binding site motif in itself provides insufficient information and a combination of inputs needs to be integrated to specify where transcription factors bind (Figure 3). (
  • Antibodies used for magnetic activated cell sorting (MACS ® ) and subset purifications were: anti-CD3, anti-CD14, and anti-CD19 (Becton Dickinson). (
  • Blockade of these interactions with antibodies directed against PD-1 or its ligands restores TH-1 immunoregulatory and T-cell cytolytic functions ( 1 , 5 , 8 , 16 ). (
  • Detection of IL-15 by Western blot or flow cytometry has proven difficult, and robust stimulation with TLR ligands is required to upregulate IL-15 to detectable levels ( 5 , 6 ). (
  • Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. (
  • Moreover, flow cytometry analyses revealed that germinal centre B cells in NOD failed to down-regulate TACI. (
  • Flow cytometry analysis showed that this transition required cell contact and was thus ligand-dependent. (
  • Transcriptional regulation of gene expression provides the basis for the responsiveness of cells to external stimuli such as changing microenvironment, infectious interlopers, or chemokine gradients. (
  • While NF-κB gene knock-out (KO) studies, next-generation sequencing, and advances in computational biology have provided us with a wealth of information regarding the transcriptional outcomes of NF-κB signaling, there is still much to be learned about the signaling process itself, which is complicated by cell type-, tissue-, and stimulus-specific variability in signaling components and their spatio-temporal dynamics. (
  • In addition transcriptional activity and IL-6 release from transfected cells could be inhibited by overexpression of the NF-κB-specific inhibitor κBα. (
  • Top-Flash reporter was used to examine the transcriptional activity of the beta-catenin/lymphoid enhanced factor/T-cell factor complex. (
  • Current efforts are aimed to investigate the role of sequence motifs and chromatin in cell-type-specific genomic binding and transcriptional regulation. (
  • These studies demonstrate that fibroblast-derived growth factors from the tumor environment can provide the malignant cells with a positive feedback through multiple mechanisms but that this stimulation is required only for cells from early and not late stages of tumor progression. (
  • The functional units of tissues contain many different cell types that continuously communicate with one another through a variety of mechanisms. (
  • The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance) and the increase in bioavailable insulin-like growth factor I (IGF-I) appear to have a role in tumor initiation and progression in insulin-resistant patients. (
  • We have developed live-cell imaging methods for studying FGFR dynamics to investigate mechanisms that coordinate the interplay between receptor trafficking and signal transduction. (
  • The molecular mechanisms and the factors involved in the progression of tumors from an estrogen (E2)-dependent to an E2-independent phenotype are not entirely understood. (
  • Functional cross talk between insulin-like growth factor-I (IGF-I) system and estrogen signaling has been largely reported, although the underlying molecular mechanisms remain to be fully elucidated. (
  • Despite the plethora of organs and cell types that depend on RANK function, little is known about the regulatory mechanisms that govern its functions both in normal cells and cancer cells. (
  • The mechanisms underlying the regulatory synergies of EMT/stem cell reprogramming are only beginning to emerge, but it is known that they can involve cooperation between various DNA-binding proteins called transcription factors. (
  • Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment through several cross-talk mechanisms. (
  • Instead, Ca 2+ enters the cell across either the plasma membrane or the membrane of intracellular organelles. (
  • Here, we report on a bioorthogonal chemistry based fluorescent probe, which is capable of monitoring intracellular thiols in living cells for up to 36 hours with an obvious blue-to-green fluorescence change. (
  • These are powerful tools to visualize the activity of phagocytic cells in real time and shed light on the intriguing paradoxical roles of these cells in both limiting infection and supporting the dissemination of intracellular pathogens. (
  • We conclude that intracellular expression of MIF in breast cancer cells is beneficial, whereas extracellular MIF may play a pro-oncogenic role in promoting breast cancer cell-stroma interactions. (
  • We studied this feedback from fibroblasts to melanoma cells by overexpressing insulin-like growth factor 1 (IGF-1) with an adenoviral vector. (
  • A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parson's lab at King's College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinson's. (
  • IR-A was preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney and had a relatively increased proportion of isoform A. IR-A expression was also increased in several tumors including those of the breast and colon. (
  • Christensen and his colleagues at the University of Copenhagen in Denmark and the Albert Einstein School of Medicine in the Bronx studied the primary cilia in lab cultures of mice fibroblasts, the cells that along with related connective tissues sculpt the bulk of the mammalian body. (
  • Emerging evidence suggests that ROS regulate diverse physiological parameters ranging from the response to growth factor stimulation to the generation of the inflammatory response, and that dysregulated ROS signaling may contribute to a host of human diseases. (
  • Also important are chemokines that induce recruitment of leukocyte subsets and bone-resorptive factors that are largely produced by recruited inflammatory cells. (
  • On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. (
  • NF-κB signaling is activated by numerous discrete stimuli and is a master regulator of the inflammatory response to pathogens and cancerous cells, as well as a key regulator of autoimmune diseases. (
  • Non-steroidal anti-inflammatory drug (NSAID) activated gene (NAG-1) is a member of the transforming growth factor-beta (TGF-beta) superfamily. (
  • Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and mediator of acute and chronic inflammatory diseases. (
  • Leukotrienes and tumor necrosis factor-α have been implicated as important mediators of leukocyte adhesion and transmigration during venous stasis 12 13 and have been demonstrated to induce selectin expression in several inflammatory models. (
  • To receive news and publication updates for Stem Cells International, enter your email address in the box below. (
  • For more than a decade, MSC has been a highly promising stem cell source and extensively investigated for its therapeutic potentials [ 3 , 4 ]. (
  • Unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), MSCs are inherently more relevant to clinical applications due to the lack of ethical and safety issues, despite lower developmental versatility [ 5 ]. (
  • MSCs and similar mesodermal stem/progenitor cells have been shown to repair and/or regenerate a wide variety of damaged/defective organs, including bone, cartilage, muscle, heart, and skin [ 6 - 10 ]. (
  • Following the hypothesis that blood vessels throughout the body serve as a systemic reservoir of multipotent stem/progenitor cells, we and other researchers have identified, purified, and characterized distinct populations of MSC-like multilineage precursors from the vasculature of multiple human organs [ 17 , 22 ]. (
  • A generalized marrow dysfunction with an abnormal bone marrow stroma (in terms of its ability to support and maintain hematopoiesis) is thought to be present in addition to a stem cell defect. (
  • The primary ligand for kit receptor is stem cell factor (SCF). (
  • In order to do that, certain traits need to be developed in a process called cancer cell plasticity, which is regulated by the epithelial mesenchymal transition (EMT) and the interrelated acquisition of certain cancer stem cell-like features. (
  • The researchers also showed that expression of NKG2D-DAP10 induced cancer stem cell-like attributes that are known to overlap with progression through EMT, and therefore are vital for cancer cell plasticity. (
  • It may be important to note that while osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells. (
  • Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. (
  • Transplantation of c-Kit+ SMG stem/progenitor cells regenerated irradiated mouse SMGs. (
  • During SMG development, epithelial end buds express c-Kit whereas its ligand, stem cell factor (SCF), is produced by the mesenchyme and epithelia. (
  • The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. (
  • 3 . A method for preventing or reducing reactivation of activated T cells comprising: contacting T cells that have been previously activated by an alloantigen with at least one member selected from the group consisting of mesenchymal stem cells and a supernatant from a mesenchymal stem cell culture in an amount effective to suppress restimulation of said activated T cells. (
  • 5 . The method of claim 4 wherein the member is mesenchymal stem cells autologous to the recipient. (
  • 7 . The method of claim 6 , wherein the mesenchymal stem cells are obtained from the donor of the transplant. (
  • 13 . The method of claim 4 , wherein the member is mesenchymal stem cells administered to the recipient prior to administration of the transplant. (
  • 14 . The method of claim 4 , wherein the member is mesenchymal stem cells administered concurrently with administration of the transplant. (
  • 15 . The method of claim 4 , wherein the member is mesenchymal stem cells administered as a part of the transplant. (
  • 17 . The method of claim 4 wherein the member is mesenchymal stem cells administered to the transplant recipient to treat rejection of the transplant by the recipient. (
  • 18 . The method of claim 4 , wherein the member is human mesenchymal stem cells. (
  • One of the defining "hallmarks" of cancer is metastasis, i.e. the ability of tumor cells to advance from their site of origin, invade surrounding tissue, enter the circulation, and establish new tumor growth at distant body parts. (
  • Sharing an architectural 3D similarity with the atherogenic and angiogenic chemokine interleukin-8 (IL-8)/CXCL8, MIF was found to function as a non-cognate ligand of CXCR2 and as chemokine-like function (CLF) chemokine. (
  • 6 Second, chemokines, including C-C motif chemokine (CCL)2, 3, 4, and 22, have an important role in chemo-attraction of cells towards the tumor microenvironment (TME). (
  • The neural retina is fully differentiated at the macula at 19-20 WG, while neuronal progenitor cells are present throughout the rest of the retina. (
  • Increasing evidence further suggests that MSCs and some tissue-specific progenitor cells are anatomically and functionally associated with vascular/perivascular niches in various tissues [ 18 - 21 ]. (
  • Therefore, we hypothesize that c-Kit signaling is required for the maintenance/expansion of SMG progenitor cells. (
  • In summary, Fgf10/Fgr2b signaling maintains c-Kit progenitor cells during development by regulating SCF and c-Kit expression. (
  • We therefore excluded genes associated with the cell cycle, and markers of differentiated neurons, from further analyses. (
  • Localization of PEDF and Eph-A6 mRNAs in sections of macaque retina shows expression of both genes concentrates in the ganglion cell layer (GCL) at the developing fovea, consistent with an involvement in definition of the foveal avascular area. (
  • Because the axons of macular ganglion cells exit the retina from around 8 WG, we suggest that the axon guidance genes highly expressed at the macula at 19-20 WG are also involved in vascular patterning, along with PEDF and NPPB . (
  • These results underscore the role of MAPK as signal-transducing molecules controlling the expression of different genes relevant to leukocyte biology upon Fc gamma R stimulation. (
  • The clinical course of chronic lymphocytic leukemia (CLL) differs significantly between patients with mutated (M-CLL) and unmutated (U-CLL) immunoglobulin (Ig) variable heavy-chain (V H ) genes, implying a role for B-cell receptor (BCR) signaling in the pathogenesis of this disease. (
  • These data demonstrate that only sustained BCR signaling can promote survival of CLL B cells and indicate that the main difference between CLL with mutated and unmutated V H genes may reside in the availability of such stimulation. (
  • 3 - 9 In contrast, CLL B cells from patients with stable disease usually express IgM encoded by mutated Ig V H genes and do not express ZAP-70. (
  • The up-regulation of these genes occurred in the absence of any additional stimulation, in an autocrine manner. (
  • Although GR is expressed throughout the body, the genes regulated and the genomic loci bound by GR show little overlap between cell-types. (